Minimum-MU and sparse-energy-layer (MMSEL) constrained inverse optimization method for efficiently deliverable PBS plans.
The deliverability of proton pencil beam scanning (PBS) plans is subject to the minimum monitor-unit (MU) constraint, while the delivery efficiency depends on the number of proton energy layers. This work develops an inverse optimization method for generating efficiently deliverable PBS plans. The proposed minimum-MU and sparse-energy-layer (MMSEL) constrained inverse optimization method utilizes iterative convex relaxations to handle the nonconvexity from minimum-MU constraint and dose-volume constraints, and regularizes group sparsity of proton spots to minimize the number of energy layers. The tradeoff between plan quality and delivery efficiency (in terms of the number of used energy layers) is controlled by the objective weighting of group sparsity regularization. MMSEL consists of two steps: first minimize for appropriate energy layers, and then with selected energy layers solve for the deliverable PBS plan. The solution algorithm for MMSEL is developed using alternating direction method of multipliers (ADMM). Range and setup uncertainties are modelled by robust optimization. MMSEL was validated using representative prostate, lung, and head-and-neck (HN) cases. The minimum-MU constraint was strictly enforced for all cases, so that all plans were deliverable. The number of energy layers was reduced by MMSEL to 78%, 76%, and 61% for prostate, lung and HN, respectively, while the similar plan quality was achieved. The number of energy layers was reduced by MMSEL to 54%, 57%, and 37% for prostate, lung and HN, respectively, while the plan quality was comprised and acceptable. MMSEL is proposed to strictly enforce minimum-MU constraint and minimize the number of energy layers during inverse optimization for efficiently deliverable PBS plans. In particular, the preliminary results suggest MMSEL potentially enables 25% to 40% reduction of energy layers while maintaining the similar plan quality.


What do women want? Facialmetric assessment of multiple motives in the perception of male facial physical attractiveness.
The multiple motive hypothesis of physical attractiveness suggests that women are attracted to men whose appearances elicit their nurturant feelings, who appear to possess sexual maturity and dominance characteristics, who seem sociable, approacheable, and of high social status. Those multiple motives may cause people to be attracted to individuals who display an optimal combination of neotenous, mature, and expressive facial features, plus desirable grooming attributes. Three quasi-experiments demonstrated that men who possessed the neotenous features of large eyes, the mature features of prominent cheekbones and a large chin, the expressive feature of a big smile, and high-status clothing were seen as more attractive than other men. Further supporting the multiple motive hypothesis, the 2nd and 3rd studies indicated that impressions of attractiveness had strong relations with selections of men to date and to marry but had a curvilinear relation with perceptions of a baby face vs. a mature face.


New molecular target for modulation of aging process.
Despite many endeavors, no satisfactory strategy has emerged for modulating the aging process, most probably because they were based on faulty rationales. In an extension of the "gate theory of aging" that we proposed recently, we propose here that caveolin, an essential component of caveolae structure, may offer a potential target for modulating the aging process. According to the gate theory, certain biomolecules such as caveolins, amphiphysins, G proteins, and integrins play decisive roles in determining the senescent phenotype and thus provide targets for modulating the aging process. Among these molecules, we chose caveolin, because it can associate with a variety of regulatory and structural molecules via their scaffolding domains and thereby influence a broad spectrum of biological phenomena including both the physiology and morphology of the senescent cells. This is an attempt to review the vast body of evidence available in the literature, both direct and indirect, supporting the accord of this pivotal role to the caveolin in the background of the gate theory for the aging process.


Evolution of developmental strategies in parasitic hymenoptera.
Parasitoid wasps have evolved a wide spectrum of developmental interactions with hosts. In this review we synthesize and interpret results from the phylogenetic, ecological, physiological, and molecular literature to identify factors that have influenced the evolution of parasitoid developmental strategies. We first discuss the origins and radiation of the parasitoid lifestyle in the Hymenoptera. We then summarize how parasitoid developmental strategies are affected by ecological interactions and assess the inventory of physiological and molecular traits parasitoids use to successfully exploit hosts. Last, we discuss how certain parasitoid virulence genes have evolved and how these changes potentially affect parasitoid-host interactions. The combination of phylogenetic data with comparative and functional genomics offers new avenues for understanding the evolution of biological diversity in this group of insects.


Detailed assessment of pedestrian ground contact injuries observed from in-depth accident data.
Most pedestrians struck by vehicles receive injuries from contact with the vehicle and also from the subsequent ground contact. However, ground related pedestrian injuries have received little focus. This paper uses 1221 German pedestrian collision cases occurring between 2000 and 2015 to assess the distribution and risk factors for pedestrian ground related injuries. Results show that for MAIS 2, the ground accounted for 24% of cases, for MAIS 3 the ground accounted for 20% of cases and for MAIS 4-5, the ground accounted for 14% of cases. There were no AIS 6 ground related injuries, though there were several fatal cases where the ground was coded as the most serious injury. The head, thorax and spine dominate AIS 4-5 ground contact injuries. Vehicle impact speeds were higher for ground related AIS 4-5 compared to AIS 2 injury cases and the average impact speed for ground related injuries to the upper and lower extremities was lower than for body regions like head, thorax and spine. There was a significant age effect on pedestrian ground related injury outcome, with older pedestrians suffering more severe injuries and the median age for thorax injuries was higher than for all other body regions. There was no significant difference in the proportions of AIS 2+ head injuries produced by ground contact for more recent vehicles (model year since 2005) compared to older vehicles (model year before 2005). However, logistic regression analysis showed that the normalised bonnet leading-edge height is a risk factor for adult pedestrian AIS2+ ground related head injuries, and this provides empirical support for recent computational modelling predictions which implied a relationship between vehicle shape and pedestrian ground contact injuries. Considering the potential benefits of preventing pedestrian ground contact, for collisions below 40km/h two thirds of the injury costs would be eliminated if ground contact could be prevented, and even higher benefits are likely at lower speeds (20 and 30km/h). These data demonstrate the importance of ground related pedestrian injuries and show that vehicle shape influences pedestrian injury outcome in ground contact. The data therefore provides significant motivation for countermeasures to prevent or moderate pedestrian ground related injuries.


Immunoreactive tyrosine hydroxylase in the brain and pituitary gland of the platyfish.
Immunoreactive tyrosine hydroxylase (ir-TH), the rate-limiting enzyme for the synthesis of dopamine and other catecholamines, was localized in the brain and pituitary gland of sexually mature platyfish (Xiphophorus maculatus). This is the first report of ir-TH in the nucleus olfactoretinalis, an LHRH-containing nucleus in the brain which plays an important role in the development and functioning of the reproductive system in platyfish. Ir-TH was also localized in the nucleus preopticus and paraventricular organ. In the pituitary gland ir-TH is found in the prolactin cells and in some fish, in some of the gonadotropin-containing cells of the pars intermedia, but not in the gonadotrops of the pars distalis. The localization of ir-TH in brain centers and pituitary cells associated with reproductive system regulation is discussed in the context of the interaction of monamines, neuropeptides and pituitary hormones during the maturation and operation of the brain-pituitary-gonadal axis.


A plaque-purified rabies virus (strains V-319) derived from a vampire bat (Desmodus rotundus) in Mexico: vaccine potential.
A plaque-purified experimental rabies vaccine was developed from an isolate (strain V-319) made from a naturally infected vampire bat (Desmodus rotundus). Two different vaccines were prepared; one was live virus and the second was an inactivated rabies virus preparation. The live virus vaccine, as well as a betapropiolactone-inactivated vaccine, gave complete protection to challenge inoculation after 1 year. In contrast, greater than 80% of the non-vaccinated experimental control cattle died of rabies. The live virus vaccine could be given at doses as low as 10(5) PFU without loss of efficacy. It did not cause adverse reactions. More than 10,000 cattle have been vaccinated with the live virus vaccine under field conditions. No rabies deaths occurred in vaccinated cattle during a 2-year postvaccinal period. The serological responses of vaccinated cattle indicated protection that endured at least 1 year.


Genetic and functional characterization of dpp genes encoding a dipeptide transport system in Lactococcus lactis.
The genes encoding a binding-protein-dependent ABC transporter for dipeptides (Dpp) were identified in Lactococcus lactis subsp. cremoris MG1363. Two (dppA and dppP) of the six ORFs (dppAdppPBCDF) encode proteins that are homologous to peptide- and pheromone-binding proteins. The dppP gene contains a chain-terminating nonsense mutation and a frame-shift that may impair its function. The functionality of the dpp genes was proven by the construction of disruption mutants via homologous recombination. The expression of DppA and various other components of the proteolytic system was studied in synthetic and peptide-rich media and by using isogenic peptide-transport mutants that are defective in one or more systems (Opp, DtpT, and/or Dpp). In peptide-rich medium, DppA was maximally expressed in mutants lacking Opp and DtpT. DppA expression also depended on the growth phase and was repressed by tri-leucine and tri-valine. The effect of tri-leucine on DppA expression was abolished when leucine was present in the medium. Importantly, the Dpp system also regulated the expression of other components of the proteolytic system. This regulation was achieved via the internalization of di-valine, which caused a 30-50% inhibition in the expression of the proteinase PrtP and the peptidases PepN and PepC. Similar to the regulation of DppA, the repressing effect was no longer observed when high concentrations of valine were present. The intricate regulation of the components of the proteolytic system by peptides and amino acids is discussed in the light of the new and published data.


Quantification of Giardia transcripts during in vitro excystation: interest for the estimation of cyst viability.
The aim of the present study was to evaluate the potential of transcript quantification as an indicator of Giardia cyst viability. The variations of beta-giardin, EF1A and ADHE mRNAs were quantified during excystation by real-time RT-PCR assays and compared with the percentages of viability estimated using propidium iodide staining and in vitro excystation. The first experiments were performed with purified G. duodenalis assemblage B cysts. When 55% of excysting protozoa were observed, the increase of the selected transcripts ranged from 0.40+/-0.13 to 0.97+/-0.11 log10 after 1h of incubation in excystation medium. Purified cysts were also stored at 4 degrees C for up to 56 days and analysed at several sampling times. Significant correlations were observed between the variations of the selected mRNAs and the percentages of viability estimated with staining and excystation methods. Among the three transcripts, beta-giardin appeared to be the most appropriate to study the viability of Giardia cysts concentrated from wastewater samples.


Locally advanced thyroid cancer: can CT help in prediction of extrathyroidal invasion to adjacent structures?
The purpose of this study was to determine the diagnostic accuracy of CT for detecting extrathyroidal invasion of thyroid cancer to adjacent structures. Eighty-four patients (19 men, 65 women; age range, 19-84 years; mean, 54.2 +/- 15.4 years) with 86 malignant tumors of the thyroid with extracapsular extension (37 T3, 49 T4) were retrospectively enrolled in this study. Two radiologists independently evaluated the CT findings of invasion of thyroid cancer into the trachea, esophagus, common carotid artery, internal jugular vein, and recurrent laryngeal nerve. These results were compared with the surgical and histopathologic findings. The mean sensitivity, specificity, and accuracy of CT were as follows: 59.1%, 91.4%, and 83.2% for tracheal invasion; 28.6%, 96.2%, and 90.7% for esophageal invasion; 75.0%, 99.4%, and 98.8% for invasion of the common carotid artery; 33.3%, 98.8%, and 97.1% for invasion of the internal jugular vein; and 78.2%, 89.8%, and 85.5% for invasion to the recurrent laryngeal nerve. Interobserver agreement was moderate to good in the five categories of extrathyroidal invasion with a mean kappa value of 0.65 (range, 0.49-0.77). Although the effectiveness is limited by low sensitivity, CT may be a valuable tool for evaluation of extrathyroidal invasion of thyroid cancer to adjacent structures.


Pulsed exposure of the macrophyte Lemna minor to herbicides and the mayfly Neocloeon triangulifer to diamide insecticides.
Pesticides applied to agricultural land can enter aquatic ecosystems through runoff or leaching during precipitation events. In a lotic system, these events result in a pulse of exposure to biota living in these systems. The concentration of pesticide increases, peaks, and then gradually declines, and this pulsed exposure may occur multiple times over the course of a growing season. The dynamic nature of exposure to pesticides in the environment is not often mimicked in the laboratory testing of the toxicity of pesticides. The present study investigated the potential latent effects of a 24-h pulsed exposure of metolachlor, metribuzin, MCPA (2-methyl-4-chlorophenoxyacetic acid), MCPP (methylchlorophenoxypropionic acid or mecoprop), dicamba, and 2,4-D to the aquatic macrophyte Lemna minor followed by a 5-day recovery period. The relative sensitivity of L. minor to the herbicides were, in this decreasing order: metolachlor > metribuzin >2,4-D > MCPA > MCPP > dicamba. This study also investigated the effects of short-term exposures of the diamide insecticides cyantraniliprole and chlorantraniliprole on the survival of the larvae of the parthenogenetic mayfly Neocloeon triangulifer. The median lethal concentrations (96-h LC50s) for cyantraniliprole and chlorantraniliprole were 8.60 and 2.92 μg/L, respectively.


Complement activation pathways associated with islet cell surface antibody (ICSA) derived from child patients with insulin-dependent diabetes mellitus (IDDM).
We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement-dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA-treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway.


Diagnosis of well-differentiated hepatocellular lesions: role of immunohistochemistry and other ancillary techniques.
There is considerable overlap in morphologic features in well-differentiated hepatocellular lesions necessitating the use of immunohistochemistry and other techniques for diagnosis. Map-like pattern with glutamine synthetase in focal nodular hyperplasia and cytoplasmic staining with serum amyloid associated protein in inflammatory hepatocellular adenoma (HA) are useful for this distinction. The distinction of well-differentiated hepatocellular carcinoma (HCC) and HA in noncirrhotic liver is facilitated by demonstrating glypican-3 and cytogenetic changes like gains of chromosomes 1 and 8. Nuclear staining with β-catenin and/or diffuse staining with glutamine synthetase strongly favors well-differentiated HCC or HA with high risk for HCC. In a cirrhotic liver, separation of early HCC from high-grade dysplastic nodule requires identification of stromal invasion, which can be highlighted by absence of keratin 7-positive ductular reaction. Combined use of heat shock protein 70, glutamine synthetase, and glypican-3 can be useful as positivity for 2 or more of these markers has shown high specificity for HCC in early studies.


The mirror lies: body dysmorphic disorder.
Body dysmorphic disorder is an increasingly recognized somatoform disorder, clinically distinct from obsessive-compulsive disorder, eating disorders, and depression. Patients with body dysmorphic disorder are preoccupied with an imagined deficit in the appearance of one or more body parts, causing clinically significant stress, impairment, and dysfunction. The preoccupation is not explained by any other psychiatric disorder. Patients present to family physicians for primary care reasons and aesthetic or cosmetic procedures. Cosmetic correction of perceived physical deficits is rarely an effective treatment. Pharmacologic treatment with selective serotonin reuptake inhibitors and nonpharmacologic treatment with cognitive behavior therapy are effective. Body dysmorphic disorder is not uncommon, but is often misdiagnosed. Recognition and treatment are important because this disorder can lead to disability, depression, and suicide.


Calcium transport in dentinogenesis.
A fundamental question in biomineralization research is the metabolism of the ionic constituents of the mineral phase. Mechanisms for the transport of Ca2+ ions have been identified and characterized in detail for various types of cells. Surprisingly little is known about osteoblasts and odontoblasts in this respect. This paper reviews what is known about calcium metabolism during dentinogenesis.


[Modulation of graft versus host disease by in vitro incubation of donor cells with deoxycoformycin and deoxyadenosine].
The combination of deoxycoformycin and deoxyadenosine was investigated for its capability to deplete T-cells from bone marrow and spleen cells and for its effect on GVHD in MHC-mismatched transplantation in rats. In vitro incubation with DCF/dADO for 18-20 hours resulted in significant but incomplete T-cell depletion without toxicity towards CFU-M. This corresponded with a lower incidence and a modification of GVHD following transplantation of such treated cells into MHC-incompatible recipient rats. However, GVHD could not be completely prevented by the in vitro treatment of donor cells.


Diagnosis and treatment of severe pediatric pulmonary hypertension.
Advances in the treatment of pulmonary hypertension during the past decade have dramatically improved patient survival. Many of these advances are based on improved understanding of the vascular biology of the normal and hypertensive pulmonary circulations. Pulmonary hypertension is an important determinant of morbidity and mortality in patients with many pediatric diseases, including congenital heart disease. This article describes current diagnostic strategies and treatments for patients with primary and secondary pulmonary hypertension.


Antivenom Efficacy in Neutralizing Histopathological Complications Following Latrodectus dahli Envenomation.
Nowadays use of specific antivenin for latrodectism is considered as the most effective treatment in the world. This study was undertaken to investigate the efficacy of specific antivenom against histopathological complications caused by Latrodectus dahli venom on liver, heart and kidneys tissues within 72h. Two groups were selected, each one contained 6 male New Zealand rabbits weighing 2±0.5kg. The animals were anesthetized with 0.5ml ketamine and 0.5ml xylazine by intramuscular route. The L. dahli venom (0.5mg/kg) was injected subcutaneously to both the groups. The second group of rabbits 24h after the venom injection received specific antivenom by intravenous route. Seventy-two hours after the venom and antivenom injections, the rabbits were dissected to obtain heart, liver and kidney tissues. The tissues were stained by hematoxylin and eosin stains and histopathological studies were examined by optical microscope. In group one, the venom induced myocytolysis, myocarditis, coagulation necrosis in the heart tissue and the liver tissue showed central vein congestion, congested vessels, dilated sinusoids and inflammation. However, no significant histopathological complications were observed in kidney tissues. In the second group, antivenom injection greatly prevented escalation of the complications on foresaid tissues. Latrodectus dahli venom induces histopathological complications on vital organs. Specific antivenom injection, 24h after the venom injection, could protect the tissues from incidence and intensification of histopathological complications. Future studies in human beings should be conducted to assess the protection against the specific-Latrodectus antivenin.


Smoke screen: an ethnographic study of a cigar shop's collective rationalization.
It is the purpose of this ethnographic study to explain why efforts from the medical establishment, the press, and friends and family are unsuccessful in persuading a group of men at a local cigar shop to stop smoking. I also seek to determine how these men create a linguistic defense shield that, ironically, protects them from the anxiety that such messages are designed to produce. I argue that the regulars at the shop collectively craft and share 6 prosmoking arguments that (a) rebuke the findings of the medical establishment, (b) anesthetize the regulars from the impact of antismoking messages, and (c) relieve cognitive dissonance and anxiety created by the act of smoking. I establish a theoretical foundation for the study, describe how the regulars craft and converge their collective narratives, and detail the 6 collectively created prosmoking narratives most frequently used by the regulars in countering antismoking messages.


[An electrochemical method of determining peroxidase in saliva].
Electrochemical method has been developed for measuring human salivary peroxidase. Salivary peroxidase levels were measured in donors in various hours of the day, in girls in various periods of the cycle, and in myocardial infarction patients. The results may be used to develop rapid methods for assessment of ovarian functional activity and for prediction of myocardial infarction outcome. Electrochemical analysis productivity is 360 samples per hour, the minimal peroxidase concentration detectable is 5.10(-12) M.


Analyzing Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis: Potential Role of L-carnitine.
Mitochondrial dysfunction, apoptosis and oxidative stress, are the interrelated events underlining the pathology of numerous diseases including cardiovascular, neurologic, and metabolic disorders. Due to playing a critical role in glucose and fatty acids' metabolism, L-carnitine probably has the potential to adjust these unfavorable events. The present review has evolved based on existing literature that investigated the mechanisms of L-carnitine and its derivatives based mitochondrial dysfunction, oxidative stress, and apoptosis related modulation. The released studies have been searched with the databases including Google Scholar, Scopus, and PubMed out of which overall 76 full-length articles have been chosen and recruited in this review. L-carnitine exerts protective effects against these cellular events in several manners including the maintenance of mitochondrial functions and decreasing the production of reactive oxygen species at different points. In clinical setting, these effects could be applied to treat a variety of associated diseases.


Post-transcriptional gene regulation by mRNA modifications.
The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N6-methyladenosine (m6A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses. Other mRNA modifications, including N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome and collectively code a new layer of information that controls protein synthesis.


Congenital midline spinal hamartoma in an infant with DICER1 syndrome: A case report.
Congenital spinal hamartomas are rare benign tumors. They are mostly seen in infants and are typically asymptomatic at presentation. Spinal hamartomas have not been associated with any known cancer predisposition syndrome. DICER1 syndrome is a well-characterized cancer predisposition syndrome caused by a germline mutation in the DICER1 gene, which shows variable expressivity. To our knowledge, spinal hamartoma has never been described in individuals with DICER1 syndrome. Here, we describe a rare association of congenital spinal hamartoma and DICER1 syndrome in a 5-week-old infant, with molecular findings suggestive of the implication of DICER1 in the pathogenesis of this tumor.


Reading impairment and visual processing deficits in schizophrenia.
Individuals with schizophrenia show magnocellular visual pathway abnormalities similar to those described in dyslexia, predicting that reading disturbance should be a common concomitant of schizophrenia. To date, however, reading deficits have not been well established, and, in fact, reading is often thought to be normal in schizophrenia based upon results of tests such as the WRAT, which evaluate single word reading. This study evaluated "real world" reading ability in schizophrenia, relative to functioning of the magnocellular visual pathway. Standardized psychoeducational reading tests and contrast sensitivity measures were administered to 19 patients and 10 controls. Analyses of between group differences were further refined by classification of participants into reading vs. non-reading impaired groups using a priori and derived theoretical models. Patients with schizophrenia, as a group, showed highly significant impairments in reading (p<0.04-p<0.001), with particular deficits on tests of rate, comprehension and phonological awareness. Between 21% and 63% of patients met criteria for dyslexia depending upon diagnostic model vs. 0-20% of the controls. The degree of deficit correlated significantly with independent measures of magnocellular dysfunction. Reading impairment in schizophrenia reaches the level of dyslexia and is associated with compromised magnocellular processing as hypothesized. Findings related to symptoms, functioning and recommendations for reading ability assessment are discussed.


[Plasma erythropoietin levels in patients with stabilized function of the transplanted kidney].
Plasma erythropoietin level was assessed in 96 kidney transplant patients with stabilized function of the graft 3 months up to 5 years after transplantation and in 16 healthy subjects. In kidney transplant patients on CyA or azathioprine respectively, plasma erythropoietin levels were significantly higher during the first three months after transplantation than in normals. Normalization of erythropoietin levels were observed 6 to 12 month after kidney transplantation. As compared with patients on CyA, in azathioprine treated patients plasma erythropoietin levels were significantly higher 12 to 60 months after transplantation. These elevated erythropoietin levels in azathioprine treated patients seem to be due also to factors other than higher prednisone dosage.


Identification of a missense mutation (G329A;Arg(110)--> GLN) in the human FUT7 gene.
The human FUT7 gene codes for the alpha1,3-fucosyltransferase VII (Fuc-TVII), which is involved in the biosynthesis of the sialyl Lewis x (SLe(x)) epitope on human leukocytes. The FUT7 gene has so far been considered to be monomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by Western blot analysis using monoclonal antibodies directed against SLe(x) and SLe(x)-related epitopes. One individual showed lower levels of SLe(x) expression and an elevated expression of CD65s compared to controls. The coding regions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg(110) --> Gln) was found in one allele, whereas the other FUT7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 cells transiently transfected with the mutated FUT7 construct. The FUT7 Arg(110) is conserved in all previously cloned vertebrate alpha 1,3-fucosyltransferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of < or =1% for this mutation was found (3 heterozygotes). Genetic characterization of the family members of one of the additional heterozygotes identified one individual carrying the G329A mutation in both FUT7 alleles. Peripheral blood neutrophils of this homozygously mutated individual showed a lowered expression of SLe(x) and an elevated expression of CD65s when analyzed by Western blot and flow cytometry. The homozygous individual was diagnosed with ulcer disease, non-insulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome but had no history of recurrent bacterial infections or leukocytosis.


Crystallization of trehalose in frozen solutions and its phase behavior during drying.
(i) To study the crystallization of trehalose in frozen solutions and (ii) to understand the phase transitions during the entire freeze-drying cycle. Aqueous trehalose solution was cooled to -40°C in a custom-designed sample holder. The frozen solution was warmed to -18°C and annealed, and then dried in the sample chamber of the diffractometer. XRD patterns were continuously collected during cooling, annealing and drying. After cooling, hexagonal ice was the only crystalline phase observed. However, upon annealing, crystallization of trehalose dihydrate was evident. Seeding the frozen solution accelerated the solute crystallization. Thus, phase separation of the lyoprotectant was observed in frozen solutions. During drying, dehydration of trehalose dihydrate yielded a substantially amorphous anhydrous trehalose. Crystallization of trehalose, as trehalose dihydrate, was observed in frozen solutions. The dehydration of the crystalline trehalose dihydrate to substantially amorphous anhydrate occurred during drying. Therefore, analyzing the final lyophile will not reveal crystallization of the lyoprotectant during freeze-drying. The lyoprotectant crystallization can only become evident by continuous monitoring of the system during the entire freeze-drying cycle. In light of the phase separation of trehalose in frozen solutions, its ability to serve as a lyoprotectant warrants further investigation.


Antibody prevalence of hog cholera, bovine viral diarrhoea and Aujeszky's disease virus in wild boars in northern Germany.
During the hunting season 1990/1991 a total of 841 blood samples was collected from shot wild boar corresponding to about 2.11% of the total hunting bag in Lower Saxony. All the sera were screened for neutralizing antibodies (nAb) to hog cholera virus (HCV) and bovine viral diarrhoea virus (BVDV) by direct neutralizing peroxidase linked antibody (NPLA) assay. For the detection of antibodies (Ab) against HCV a Complex Trapping Blocking (CTB) ELISA was used. Cytotoxic sera were retested using an indirect immunoperoxidase technique. Additionally all sera were tested for antibodies to Aujeszky's disease virus (ADV) in a commercial indirect ELISA and 722 sera for ADV nAb in a virus neutralization test (VNT) with and without the addition of guinea pig complement. Screening of 841 sera yielded six sera neutralizing HCV strain ALFORT/187 and two sera with a positive CTB-ELISA reaction. A total of seven sera not identical with the HCV seropositive sera yielded BVDV neutralizing antibodies. The majority of HCV nAb positive samples were found in a region close to the former border to the German Democratic Republic (GDR) west of the State of Sachsen-Anhalt. Screening for ADV detected five sera positive in ELISA amongst 12 sera yielding nAb against ADV. Positive samples were obtained in the regions of Brunswick, Lüneburg and Hannover.


Particle-size distribution of very low density plasma lipoproteins during fat absorption in man.
The size distributions of electrophoretically isolated subfractions of the very low density human plasma lipoproteins have been determined using electron microscopy. The primary and secondary particles observed in plasma of normal subjects after fat ingestion appear to have similar size distributions. Particles produced by corn oil feeding can be fixed by the osmium tetroxide reaction while those produced by butter fat feeding could not be fixed or made visible by this technique. Good agreement between particle size as measured by electron microscopy and particle size as predicted by ultra-centrifugal analysis was obtained.


Prevalence and Clinical Differences of Suicidal Thoughts and Behaviors in a Community Sample of Youth Receiving Cognitive-Behavioral Therapy for Anxiety.
This study examined the incidence of suicidal thoughts and behaviors in youth with anxiety before initiating cognitive behavioral therapy, as well as the emergence of suicidal thoughts and behaviors during treatment. Overall, 30% of youth experienced suicidal thoughts and behaviors. Prior to treatment, 24% reported suicidal thoughts and behaviors, and 13.1% endorsed suicidal thoughts and behaviors during treatment. More than half who endorsed suicidal thoughts and behaviors during treatment were newly identified cases not detected prior to treatment. Disagreement among parent- and child-report measures of suicidality was found at baseline. Youth who experienced suicidal thoughts and behaviors had higher levels of loneliness, depressive symptoms, overt peer victimization, functional impairment, and externalizing symptoms. Findings suggest that the assessment of suicidality at a single time-point and from one informant is not sufficient to identify at-risk youth. Ongoing assessment of suicidal risk during treatment is important in this population.


Left infrarenal region: anatomic variants, pathologic conditions, and diagnostic pitfalls.
Computed tomography (CT) is the preferred method for evaluating the left periaortic infrarenal region. Structures larger than 11 mm in cross-sectional diameter in this region are considered abnormal and should be evaluated for lymphadenopathy, hydroureter, or a vascular abnormality such as venous thrombosis or varicoceles. Normal structures include inferior mesenteric vessels, left gonadal vein and artery, and ureter. The diagnostic process may be complicated by variations in anatomy, including double inferior vena cava, left inferior vena cava, retroaortic left renal vein, circumaortic left renal vein, horseshoe kidney, crossed-fused renal ectopia, renal agenesis, and ureteral duplication. Familiarity with the anatomy of this region and awareness of normal variants are necessary to avoid errors in diagnosis. Radiologists should also be aware of problems in CT technique (nonopacified bowel, dynamic and unenhanced scanning) that can confuse the diagnosis.


Professional identity formation within longitudinal integrated clerkships: A scoping review.
Although the uptake of Longitudinal Integrated Clerkships (LICs) is increasing worldwide, and there are documented benefits to participation, there is a lack of conceptual evidence regarding how LICs exert many of their benefits, including their influence on the recruitment and retention of practitioners to underserved areas or specialties. Whilst career choice and professional identity development have been previously connected within medicine, what is known about the ways in which LICs influence identity remains unclear. A scoping review was conducted to explore current knowledge and map directions for future research. In 2020, the authors searched nine bibliographic databases for articles discussing identity within the context of LICs using a systematic search strategy. Two reviewers independently screened all articles against eligibility criteria and charted the data. Eligible articles were analysed by quantitative and qualitative thematic analysis. 849 articles were identified following an extensive search. 131 articles were selected for full-text review, with 27 eligible for inclusion. Over half of all articles originated from the United States or Canada, and research most frequently explored identity development from sociocultural orientations. Qualitatively, four themes were identified: (a) The importance of contextual continuities; (b) Symbiotic relationship of responsibility and identity development; (c) Becoming a competent carer; and (d) Influence of LICs on career identity. This scoping review adds weight to the supposition that participation in LICs facilitates identity development, namely through contextual continuities and the responsibility students assume as they become co-providers of patient care. There are suggestions that LICs encourage the development of an 'ethic of caring'. As little research compares comprehensive LICs with other clerkship models, it remains difficult to say to what degree identity formation is facilitated above and beyond other models. Future comparative research, and research exploring identity formation from diverse theoretical perspectives would add depth.


Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice.
The recent availability of mice lacking the neuronal form of the vesicular monoamine transporter 2 (VMAT2) affords the opportunity to study its roles in storage and release. Carbon fiber microelectrodes were used to measure individual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 is indispensable for monoamine storage because mast cells from homozygous (VMAT2(-/-)) mice, while undergoing granule-cell fusion, do not release monoamines. Cells from heterozygous animals (VMAT2(+/-)) secrete lower amounts of monoamine per granule than cells from wild-type controls. Investigation of corelease of histamine and 5-HT from granules in VMAT2(+/-) cells revealed 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role.


Public timber supply, market adjustments, and local economies: economic assumptions of the Northwest Forest Plan.
The Northwest Forest Plan in the Pacific Northwest sought to stabilize local economies, including local employment and income, by stabilizing the flow of wood fiber from public forests. This is also a common forest management objective in other regions and countries. Because this economic strategy ignores basic market adjustments, it is likely to fail and to unnecessarily damage forest ecosystems. Application of basic economic principles on how markets operate significantly changes the apparent efficacy of efforts to manage local economies by managing timber supply. The emphasis on timber supply tends to ignore the dominant role that the demand for wood fiber and wood products, rather than wood-fiber supply, plays in determining levels of harvest and production. Contemporary economics indicates that markets tend to operate to offset reductions in wood-fiber supply. This significantly moderates the economic cost of reducing commercial timber harvest in the pursuit of environmental objectives. In addition, contemporary economic analysis indicates that the economic links between natural forests and local communities are much broader than simply the flow of commercially valuable logs to manufacturing facilities. At least in the United States, the flow of environmental services from natural forests has increasingly become an amenity that has drawn people and economic activity to forested areas. Attractive site-specific qualities, including those supported by natural forests, can potentially support local economic development even in the face of reduced timber harvests. These market-related adjustments partially explain the Northwest Forest Plan's overestimation of the expected regional impacts associated with reduced federal timber supply and the ineffectiveness of the plan's efforts to protect communities by stabilizing federal timber supply


Phosphatidylinositol-3-kinase-Akt kinase and p42/p44 mitogen-activated protein kinases mediate neurotrophic and excitoprotective actions of a secreted form of amyloid precursor protein.
The alpha-secretase-derived form of the amyloid precursor protein (sAPPalpha), which is released from neurons in an activity-dependent manner, has been shown to promote long-term survival of hippocampal and cortical neurons in culture and can protect those neurons against excitotoxic and ischemic injury in culture and in vivo. The signal transduction pathway(s) activated by sAPPalpha has not been established. We now report that sAPPalpha activates the phosphatidylinositol-3-kinase (PI(3)K)-Akt kinase signaling pathway in cultured hippocampal neurons. sAPPalpha also stimulates phosphorylation of p42 (ERK1) and p44 (ERK2) mitogen-activated protein (MAP) kinases by a PI(3)K-independent pathway. Treatment of neurons with sAPPalpha protects them against death induced by trophic factor deprivation and exposure to glutamate, and these survival-promoting effects of sAPPalpha are abolished or attenuated when either PI(3)K or p42/p44 MAP kinases are selectively blocked. Exposure of neurons to sAPPalpha resulted in a decrease in the level of IkappaBbeta and an increase in NF-kappaB DNA binding activity, both of which were blocked by wortmannin, suggesting that the transcription factor NF-kappaB may be a downstream target of the PI(3)K-Akt pathway that may play a role in the cell survival-promoting action of sAPPalpha. These findings suggest that the PI(3)K-Akt pathway and p42/p44 MAP kinases mediate responses of neurons to sAPPalpha in physiological and pathological settings, with implications for synaptic plasticity and the pathogenesis of Alzheimer's disease.


Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.
A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity. In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD) or normal chow diet (CD), as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1) were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA) induced endothelial cells apoptosis and regulation of cytokine gene expression. Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.


COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.
Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.


Prevalence of Bacillus anthracis-like organisms and bacteriophages in the intestinal tract of the earthworm Eisenia fetida.
Stable infection of Bacillus anthracis laboratory strains with environmental bacteriophages confers survival phenotypes in soil and earthworm intestinal niches (R. Schuch and V. A. Fischetti, PLoS One 4:e6532, 2009). Here, the natural occurrence of two such B. anthracis-infective bacteriophages, Wip1 and Wip4, was examined in the intestines of Eisenia fetida earthworms as part of a 6-year longitudinal study at a Pennsylvania forest site. The Wip1 tectivirus was initially dominant before being supplanted by the Wip4 siphovirus, which was then dominant for the next 3 years. In a host range analysis of a wide-ranging group of Bacillus species and related organisms, Wip1 and Wip4 were both infective only toward B. anthracis and certain B. cereus strains. The natural host of Wip4 remained constant for 3 years and was a B. cereus strain that expressed a B. anthracis-like surface polysaccharide at septal positions on the cell surface. Next, a novel metagenomic approach was used to determine the extent to which such B. cereus- and B. anthracis-like strains are found in worms from two geographical locations. Three different enrichment strategies were used for metagenomic DNA isolation, based either on the ability of B. cereus sensu lato to form heat-resistant spores, the sensitivity of B. anthracis to the PlyG lysin, or the selective amplification of environmental phages cocultured with B. anthracis. Findings from this work indicate that B. cereus sensu lato and its phages are common inhabitants of earthworm intestines.


[A psychologist's insight to understand the suffering of caregivers at work].
During their interviews with the staff psychologist, caregivers evoke numerous reasons for their unease. Difficulties relating to their work are the first to be mentioned: a search for a sense of purpose, a lack of communication with their colleagues and time with their patients. However, sometimes, this suffering felt by caregivers may be linked to deep-rooted personal issues which can reappear at work, disconcerting them in their professional practice.


CARD8 inflammasome activation triggers pyroptosis in human T cells.
Inflammasomes execute a unique type of cell death known as pyroptosis. Mostly characterized in myeloid cells, caspase-1 activation downstream of an inflammasome sensor results in the cleavage and activation of gasdermin D (GSDMD), which then forms a lytic pore in the plasma membrane. Recently, CARD8 was identified as a novel inflammasome sensor that triggers pyroptosis in myeloid leukemia cells upon inhibition of dipeptidyl-peptidases (DPP). Here, we show that blocking DPPs using Val-boroPro triggers a lytic form of cell death in primary human CD4 and CD8 T cells, while other prototypical inflammasome stimuli were not active. This cell death displays morphological and biochemical hallmarks of pyroptosis. By genetically dissecting candidate components in primary T cells, we identify this response to be dependent on the CARD8-caspase-1-GSDMD axis. Moreover, DPP9 constitutes the relevant DPP restraining CARD8 activation. Interestingly, this CARD8-induced pyroptosis pathway can only be engaged in resting, but not in activated T cells. Altogether, these results broaden the relevance of inflammasome signaling and associated pyroptotic cell death to T cells, central players of the adaptive immune system.


Discovery of genomic alterations through coregulation analysis of closely linked genes: a frequent gain in 17q25.3 in prostate cancer.
Despite its high incidence as the second most common tumor in males worldwide, primary prostate cancer has been associated with few recurrent chromosomal gains and deletions that are consistent across various studies. Few studies have explored how chromosomal alterations are coupled to abnormal gene expression. Here, we review the major genomic aberrations associated with prostate cancer and describe how detailed transcriptional and computational analyses allowed us to discover a recurrent chromosomal gain in a small region on chromosome 17. Fluorescent in situ hybridization confirmed the presence of a copy number gain in 17q25.3 in tumor-associated preneoplastic lesions of the prostate, 65% of primary tumors, and metastatic samples. These results suggest the involvement of this gain at all steps of prostate cancer progression.


Intranodal palisaded myofibroblastoma expressing DOG1: focusing on the potential diagnostic pitfalls.
Intranodal palisaded myofibroblastoma (IPM) is a rare, benign mesenchymal neoplasm of the lymph nodes with a broad differential diagnosis. We report a case of an 82-year-old woman presenting with a slow growing, right inguinal mass. The tumor arose as a circumscribed neoplasm inside a lymph node and consisted of bland spindle cells with nuclear palisading and intervening areas of amianthoid-like fibers among interstitial hemorrhage and hemosiderin-laden histiocytes in the stroma, typical histomorphological characteristics of IPM. Immunohistochemically, the neoplastic cells were positive for vimentin, smooth muscle actin (SMA), β-catenin, cyclin D1 and discovered on gastrointestinal stromal tumor (GIST) 1 (DOG1) immunostainings. A literature review and differential diagnosis of IPM are discussed. To the best of our knowledge, this is the first case of DOG1 immunoexpression in a case of IPM.


Current Trends and Research Challenges Regarding "Preparation for Oxidative Stress".
Survival under stress, such as exposure to hypoxia, anoxia, freezing, dehydration, air exposure of water breathing organisms, and estivation, is commonly associated to enhanced endogenous antioxidants, a phenomenon coined "preparation for oxidative stress" (POS). The regulation of free radical metabolism seems to be crucial under these selective pressures, since this response is widespread among animals. A hypothesis of how POS works at the molecular level was recently proposed and relies on two main processes: increased reactive species production under hypoxia, and activation of redox-sensitive transcription factors and signaling pathways, increasing the expression of antioxidants. The present paper brings together the current knowledge on POS and considers its future directions. Data indicate the presence of POS in 83 animal species (71.6% among investigated species), distributed in eight animal phyla. Three main research challenges on POS are presented: (i) to identify the molecular mechanism(s) that mediate/induce POS, (ii) to identify the evolutionary origins of POS in animals, and (iii) to determine the presence of POS in natural environments. We firstly discuss the need of evidence for increased RS production in hypoxic conditions that underlie the POS response. Secondly, we discuss the phylogenetic origins of POS back 700 million years, by identifying POS-positive responses in cnidarians. Finally, we present the first reports of the POS adaptation strategy in the wild. The investigation of these research trends and challenges may prove useful to understand the evolution of animal redox adaptations and how they adapt to increasing stressful environments on Earth.


[Mid-term follow-up results of laparoscopic radiofrequency ablation for renal cell carcinoma of T1aN0M0 stage].
To determine the effect of laparoscopic radiofrequency ablation of T1aN0M0 renal cell carcinoma (RCC) with regular follow-up. All patients underwent surgery from March 2006 to March 2009. Eight cases were solitary kidney. Twenty-two cases of left RCC and 18 cases of right RCC were diagnozed by ultrasonography and CT scanning.All of the cases were T1aN0M0 stage. No metastasis was found by iconography test. By ultrasound positioning, laparoscopic radiofrequency were performed on the renal tumor. All patients were followed up with eGFR and enhanced-CT. All patients underwent laparoscopic radiofrequency ablation surgery successfully. The mean operation time was (101 ± 19) minutes and the mean blood loss was (90 ± 14) ml (no blood transfusion pre- and post-operation). During postoperative follow-up, enhanced CT revealed complete ablation in 39 cases (the success rate was 97.5%), and 1 residue tumor was confirmed by enhanced CT 7 days post operation. This patient was under close surveillance because of solitary kidney. No progression of the residue tumor was found during the follow-up. One case of recurrence was confirmed by enhanced CT in 6 month after operation. The 3-year recurrence rate was 2.5%. No further intervation was performed on this patient and no change was found in the recurrence area during the follow-up. Both 3-year total survival rate and 3-year cancer specific survival rate were 100%. The mean eGFR was (72 ± 9) ml/(min·1.73 m(2)) in 3 years after surgery. There was no significant difference between pre-and post-operation (P > 0.05). Mid-term follow-up results show the effectiveness and safety of laparoscopic radiofrequency ablation in the treatment for T1aN0M0 RCC and have no negative influence on the renal function.


Sporadic Legionnaires' disease: clinical observations on 87 nosocomial and community-acquired cases.
To add information about sporadic Legionnaires' disease, 87 cases of L. pneumophila pneumonia were reviewed. Twenty cases were nosocomial infections and 67 cases were community-acquired. Most cases (64%) occurred between July and October. The mean age of patients was 51.4 years and males outnumbered females 2.5:1.0. Thirty-one percent of patients were receiving corticosteroid, immunosuppressive, or antineoplastic chemotherapy when illness began. Immunosuppression at onset of illness was more common in nosocomial infections (90%) than in community-acquired infections (14%). Seventy percent of patients had underlying diseases. Malignancies, renal failure, and transplantation were the most common conditions underlying nosocomial infections. Chronic lung disease and malignancies were the most common diseases underlying community-acquired infections. The case-fatality rate in nosocomial infection (70%) was greater than that in community-acquired disease (22%). Clinical, laboratory, and radiologic features of the cases were examined. Illness ranged from mild to severe. Extrapulmonary findings of encephalopathy and renal failure were more common in fatal than in non-fatal cases. Indirect immunofluorescent and microagglutination antibody responses plateaued by the fourth week of illness. Twenty-nine patients died. The case-fatality rate of patients receiving erythromycin (6%) was less than that of patients receiving penicillin (36%), ampicillin (28%), cephalosporin (32%), or aminoglycosides (41%). Despite erythromycin therapy, the case fatality rate for nosocomial L. pneumophilia pneumonia was unacceptably high (25%).


[Lymphatic endothelium in certain conditions].
Presented herein is a review of the literature data concerning the structural and functional peculiarities of the endothelium of the lymphatic and blood vessels. The authors consider the current state of the art of the problem regarding dysfunction of lymphatic endothelium dysfunctions developing in various diseases, as well as in the process of ontogenesis, pointing out an important role of impaired processes of lymphangiogenesis, underlying the development of diseases of the lymphatic system. The authors also assess administration of quercetine in treatment for chronic venous insufficiency, followed by suggesting a possible mechanism of its positive action consisting ina decrease in the oedema at early stages of lymphoedema.


Effect of elevated tropospheric ozone on the structure of bacterial communities inhabiting the rhizosphere of herbaceous plants native to Germany.
Current elevated concentrations of ozone in the atmosphere, as they are observed during summer seasons, can cause severe effects on plant vegetation. This study was initiated to analyze whether ozone-stressed plants also transfer signals below ground and thereby alter the bacterial community composition in their rhizospheres. Herbaceous plants, native to Germany, with tolerance (Anthoxanthum odoratum, Achillea millefolium, Poa pratensis, Rumex acetosa, and Veronica chamaedrys) and sensitivity (Matricaria chamomilla, Sonchus asper, and Tanacetum vulgare) to ozone, raised in the greenhouse, were exposed in open-top chambers to two different ozone regimes, i.e., "summer stress" and a normal ozone background. DNA of bacterial cells from the rhizospheres was directly extracted, and partial sequences of the 16S rRNA genes were PCR amplified with primers targeting the following phylogenetic groups: Bacteria, alpha-Proteobacteria, Actinobacteria, and Pseudomonas, respectively. The diversity of the amplified products was analyzed by genetic profiling based on single-strand conformation polymorphism (SSCP). Neither the tolerant nor the sensitive plants, the latter with visible above-ground damage, showed ozone-induced differences in any of the SSCP profiles, with the single exception of Actinobacteria-targeted profiles from S. asper. To increase the stress, S. asper was germinated and raised in the continuous presence of an elevated level of ozone. SSCP profiles with Bacteria-specific primers combined with gene probe hybridizations indicated an ozone-related increase in a Xanthomonas-related 16S rRNA gene and a decrease in the respective gene from the plant plastids. The fact that only this latter unrealistic scenario caused a detectable effect demonstrated that ozone stress has a surprisingly small effect on the structural diversity of the bacterial community in rhizospheres.


Coronary effects of a combined beta adrenoceptor blocking and calcium antagonist therapy in running dogs.
The effects of YM-16151 (1 mg/kg, i.v.), a combined beta 1-adrenoceptor blocking and calcium antagonist drug, on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs at rest and during treadmill exercise. These effects were compared to those in the same animals of nicardipine (0.1 mg/kg, i.v.), atenolol (1 mg/kg, i.v.) and their combination (at the same doses). Circumflex artery diameter (CxAD) and coronary blood flow increased and coronary vascular resistance (CVR) decreased during control exercise under saline. YM-16151 and the nicardipine-atenolol combination similarly dilated large and small coronary arteries at rest, but dilation of large conductance vessels was abolished during exercise, while CVR decreased further. Both YM-16151 and the nicardipine-atenolol combination only slightly increased the rate-pressure product at rest, but strongly opposed its exercise-induced rise. Nicardipine maximally increased CxAD, decreased CVR, and enhanced the rate-pressure product at rest and during exercise. Conversely, atenolol decreased CxAD and the rate-pressure product and increased CVR at rest, but large coronary arteries remained constricted during exercise despite the concomitant dilation of small resistance vessels. Thus, in the coronary vascular bed of conscious dogs, YM-16151 really behaves as a hybrid drug, combining beta 1-adrenoceptor blocking and calcium antagonist properties, both at rest and during exercise. As a result, YM-16151 increases oxygen supply at rest and decreases oxygen demand during exercise. Finally, this study emphasizes the major role of beta 1-adrenoceptors in the mediation of exercise-induced dilation of large coronary arteries.


[Scintigraphy of lymphomatous masses using 99mTc-MIBI].
Tc 99m sestamibi imaging is used in nuclear oncology, cardiology, but its role in detecting lymphomas has not been widely investigated. During 1998-2001 at the Department of Nuclear medicine, Kaunas University Hospital 68 patients with lymphomas (50 patients with Hodgkins disease (HD), 18 with non-Hodgkins (NHL)) underwent Tc 99m MIBI whole-body imaging. Of the 47 lymphoma lesions showed abnormal MIBI uptake. The accuracy of MIBI scintigraphy in patients with Hodgkins disease was lower (78%) compared to that of patients with non-Hodgkins lymphomas (94%). However, this difference was not related to tumor type, but to lesion size. Tumor size was significantly (p = 0.01) higher in lesions NHL with increased MIBI uptake (3.9 +/- 2.5 cm) compared with those with no uptake (1.5 +/- 0.5 cm).


[Acute encephalitis in zoster infection].
A case of herpes zoster acute meningo-encephalitis is reported. It is characterized by a profuse intra-cerebral hemorrhage on CT scan and a favorable outcome after treatment with acyclovir. The serological basis for the diagnosis, the mechanism of the encephalitis (viral invasion or immuno-allergic type of reaction), and the origin of the hemorrhagic lesion are discussed. The effectiveness of acyclovir in treating the extention of the infection to the nervous system in patients suffering from varicella-zoster is also discussed.


Socioaffective factors modulate working memory in schizophrenia patients.
Working memory deficit in schizophrenia is a core cognitive feature of the disorder and is reliably associated with abnormalities of the prefrontal circuitry. Working memory deficits are also associated with impaired social functioning and present a major obstacle toward successful rehabilitation in schizophrenia. Although the role of prefrontal cortex in working memory has been extensively investigated, the intricate relations among the prefrontal circuitry, working memory and social behaviors are not clearly understood. In this study, we manipulated social context and observed its effects on spatial working memory. In experiment 1, the effects of social and asocial reinforcements on spatial working memory were examined in schizophrenic patients and healthy controls. The results show that social but not asocial reinforcements facilitated spatial working memory in schizophrenic patients. In experiment 2, the effects of human voice reinforcements (with or without affect) on working memory was investigated. Voice reinforcements did not facilitate working memory relative to the no-reinforcement condition. There was no difference between high-affect vs flat-affect voice conditions. In experiment 3, the effects of direct and indirect social interactions on spatial working memory were studied. Direct but not indirect social interaction facilitated working memory in schizophrenic patients. These results suggest that social context might facilitate working memory in schizophrenic patients perhaps by activating frontal lobe systems. In addition, the possibility of improving cognitive functions such as working memory using seemingly non-cognitive methods might lead to potential remediation strategies.


Oxidative stress.
Much has been learnt about oxidative stress from studies of Escherichia coli. Key regulators of the adaptive responses in this organism are the SoxRS and OxyR transcription factors, which induce the expression of antioxidant activities in response to O2*- and H2O2 stress, respectively. Recently, a variety of biochemical assays together with the characterization of strains carrying mutations affecting the antioxidant activities and the regulators have given general insights into the sources of oxidative stress, the damage caused by oxidative stress, defenses against the oxidative stress, and the mechanisms by which the stress is perceived. These studies have also shown that the oxidative stress responses are intimately coupled to other regulatory networks in the cell.


UV-A Collagen Cross-Linking Treatment of Bullous Keratopathy Combined With Corneal Ulcer.
To evaluate the therapeutic effect of corneal cross-linking (CXL) in 2 cases of bullous keratopathy combined with corneal ulcer. Two patients (2 eyes) were recruited for the sake of the study. Both suffered from bullous keratopathy and presented a gradually deteriorating, vision-threatening, central corneal ulcer, despite intense local antibiotic therapy. The same surgical procedure was performed in both eyes. De-epithelialization of the affected corneas was accompanied by UV-A cross-linking and finally by the application of a therapeutic contact lens. Local antibiotic therapy was resumed after the procedure. Within 24 hours of the treatment, both patients reported significant subjective improvement of their visual acuity and ocular discomfort. Clinical evaluation revealed improvement of the corneal ulcer and the bullous keratopathy associated with significant decrease of the corneal thickness and haziness. During the 2-month follow-up period, a significant improvement of visual acuity was recorded in both cases. CXL should be considered as a potential adjuvant therapeutic tool in patients with combined bullous keratopathy and infectious keratitis, who are resistant to traditional topical therapy.


Predictive Hydration Model of Portland Cement and Its Main Minerals Based on Dissolution Theory and Water Diffusion Theory.
Efficient and accurate cement hydration simulation is an important issue for predicting and analyzing concrete's performance evolution. A large number of models have been proposed to describe cement hydration. Some models can simulate the test results with high accuracy by constructing reasonable functions, but they are based on mathematical regression and lack of physical background and prediction ability. Other models, such as the famous HYMOSTRUC model and CEMHYD3D model, can predict the hydration rate and microstructure evolution of cement based on its initial microstructure. However, this kind of prediction model also has some limitations, such as the inability to fully consider the properties of cement slurry, or being too complicated for use in finite element analysis (FEA). In this study, the hydration mechanisms of the main minerals in Portland cement (PC) are expounded, and the corresponding hydration model is built. Firstly, a modified particle hydration model of tricalcium silicate (C3S) and alite is proposed based on the moisture diffusion theory and the calcium silicate hydrate (C-S-H) barrier layer hypothesis, which can predict the hydration degree of C3S and alite throughout the age. Taking the hydration model of C3S as a reference, the hydration model of dicalcium silicate (C2S) is established, and the synergistic hydration effect of C3S and C2S is calibrated by analyzing the published test results. The hydration model of tricalcium aluminate(C3A)-gypsum system is then designed by combining the theory of dissolution and diffusion. This model can reflect the hydration characteristics of C3A in different stages, and quantify the response of the hydration process of C3A to different gypsum content, water-cement ratio, and particle size distribution. Finally, several correction coefficients are introduced into the hydration model of the main mineral, to consider the synergistic hydration effect among the minerals to some extent and realize the prediction of the hydration of PC.


Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.
Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF). Here, we investigated the role of E. histolytica MIF (EhMIF) during infection. We found that the concentration of fecal EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. Mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx, and mucosal damage. Together, these results uncover a specific parasite protein that increases mucosal inflammation, expands our knowledge of host-parasite interaction during amebic colitis, and highlights a potential immunomodulatory target.


[Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid syndrome].
To investigate a clinical role of soluble (s) CD40 ligand in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). A serum concentration of sCD40 ligand was measured with enzyme immunoassay (Bender Medsystems, Austria) in 21 patients with primary antiphospholipid syndrome (PAPS), in 25 patients with secondary APS (SAPS) associated with SLE, in 92 SLE patients and in 16 healthy donors. A sCD40 ligand concentration in sera of SAPS and SLE patients was significantly higher than in donors. Significant differences by the ligand level between the above patients were not seen. In PAPS sCD40 ligand concentration was normal. Elevated serum concentration of the ligand was observed in 9.5% patients with PAPS, 54.0%--with SAPS, 73.9%--with SLE. This rise in SLE and SAPS was not related with the disease activity or renal damage. Hyperexpression of the ligand in APS was associated neither with thromboses nor with a high concentration of IgG/IgM antibodies to cardiolipin. A direct correlation occurred between sCD40 ligand level and platelet count. In SLE and SAPS elevation of the ligand level correlated with increased thickness of carotid artery intima-media complex, hypercholesterinemia and diastolic dysfunction of left ventricular myocardium. Hyperexpression of sCD40L in SLE and SAPS is associated with developing cardiovascular diseases and atherosclerosis.


Peroxisome proliferator-activated receptor ligands in atherosclerosis.
In this review, the effect of peroxisome proliferator-activated receptor (PPAR) ligands on atherosclerosis is examined. The PPAR-gamma agonist thiazolidinediones are currently indicated for the management of Type 2 diabetes mellitus, and the PPAR-alpha agonist fibrates are used in dyslipidaemia. Here their mechanism of action and the pre-clinical and clinical evidence for the use of these medications for the prevention and treatment of atherosclerotic disease is explored. In addition, the role of PPAR-delta and the possibilities for the role of dual-binding agonists are examined.


Cellular adaptive immune response against porcine circovirus type 2 in subclinically infected pigs.
Porcine circovirus type 2 (PCV2) is a dominant causative agent of postweaning multisystemic wasting syndrome (PMWS), a multifactorial disease complex with putative immunosuppressive characteristics. Little is known about adaptive PCV2-specific immune responses in infected pigs. Therefore, the T and B cell responses following PCV2 infection in 3-week old SPF piglets infected with PCV2 or PCV2 plus porcine parvovirus (PPV) were studied. All animals were asymptomatically infected. At 7 days post infection (d p.i.), B lymphocyte and T lymphocyte numbers decreased in the dual infected, but not in the single infected piglets. At this time point a transient PCV2 viraemia was noted in the PCV2 infected groups. Antibodies against the infecting virus were detectable at day 24-28 p.i. for anti-PCV2 antibodies and at day 10 p.i. for anti-PPV antibodies, with no apparent influence of PCV2 on the early PPV antibody development. In the animals infected with PPV alone, IFN-gamma secreting cells (SC) that were not specific for PCV2 were detected by ELISPOT assay at day 7 p.i. Interestingly, this response was absent in the PCV2/PPV dual infected animals. PCV2-specific IFN-gamma SC were observed in the PCV2/PPV infected group at 7 d p.i. and in the PCV2 single infected group at 21 d p.i. A reduction in the numbers of IFN-gamma SC was observed following anti-CD4 and anti-CD8 antibody treatment, suggesting roles for both CD4+ and CD8+ T cells in the response against PCV2 infection. This was supported by an observed increase in the percentage of IFN-gamma positive CD8hi cytotoxic T cells as well as IFN-gamma positive CD8-/low helper T cells after PCV2 in vitro re-stimulation. Infection of weaned SPF piglets with PCV2 alone or combined with PPV does not induce disease and in both cases a relatively slow anti-PCV2 antibody response and weak T lymphocyte responses were found. Knowledge on such immunological characteristics is important for both PCV2 pathogenesis and vaccination.


Hypoxic pulmonary vasoconstriction during steady and pulsatile flow in ferrets.
We examined the effects of hypoxia and pulsatile flow on the pressure-flow relationships in the isolated perfused lungs of Fitch ferrets. When perfused by autologous blood from a pump providing a steady flow of 60 ml/min, the mean pulmonary arterial pressure rose from 14.6 to 31.3 Torr when alveolar PO2 was reduced from 122 to 46 Torr. This hypoxic pressor response was characterized by a 10.1-Torr increase in the pressure-axis intercept of the extrapolated pressure-flow curves and an increase in the slope of these curves from 130 to 240 Torr X l-1 X min. With pulsatile perfusion from a piston-type pump, mean pulmonary arterial pressure increased from 17.5 to 36.3 Torr at the same mean flow. This hypoxic pressor response was also characterized by increases in the intercept pressure and slope of the pressure-flow curves. When airway pressure was raised during hypoxia, the intercept pressure increased further to 25 +/- 1 Torr with a further increase in vascular resistance to 360 Torr X l-1 X min. Thus, in contrast to the dog lung, in the ferret lung pulsatile perfusion does not result in lower perfusion pressures during hypoxia when compared with similar mean levels of steady flow. Since the effects of high airway pressure and hypoxia are additive, they appear to act at or near the same site in elevating perfusion pressure.


An Algorithm for Soft Tissue Tumors: Current Perspectives.
The diagnosis and treatment of soft tissue sarcomas has dramatically changed in the last 10 to 15 years with more precise preoperative diagnosis, resection, adjunct therapy, and long-term follow-up. With correct preoperative diagnosis and staging of a soft tissue sarcoma, the surgeon, in conjunction with the radiation therapist and the medical oncologist, can select the optimal therapeutic approach to minimize the development of recurrences and metastases. Recognition of a mass as benign or non-neoplastic prevents unnecessary surgery. This article presents an algorithm that demonstrates the important interactions and contributions of the various oncologic-related disciplines (surgery, radiology, pathology, medical oncology, and radiation therapy) to the care of patients with soft tissue tumors.


Adjectives really do modify nouns: the incremental and restricted nature of early adjective acquisition.
By 24 months, most children spontaneously and correctly use adjectives. Yet prior laboratory research that has studied lexical acquisition in young children reports that children up to 3-years-old map novel adjectives to object properties only in very limited situations (Child Development 59 (1988) 411; Child Development 64 (1993) 1651; Child Development 71 (2000) 649; Developmental Psychology 36 (2000) 571; Child Development 69 (1998) 1313). In Experiments 1 and 2 we introduced 36-month-olds (Experiment 1) and 24-month-olds (Experiment 2) to novel adjectives while providing rich referential and syntactic information to indicate what the novel words mean. Specifically, we used a given novel adjective to describe multiple familiar objects which shared a salient property; in addition we used the adjectives in full noun phrases, not in conjunction with pronouns. Under these conditions, both groups mapped novel adjectives onto object properties. In Experiment 3 we asked whether the rich referential information was responsible for the successful outcome of the previous two experiments; we introduced novel adjectives to 2- and 3-year-olds as in Experiments 1 and 2, but the adjectives modified nouns of vague (very general) reference ("one", or "thing"). Under these conditions the children failed. We suggest that young word learners require access to the taxonomy of the object type so that the relevant property can be identified. The taxonomically specific nouns of Experiments 1 and 2 accomplish this, whereas the more general, semantically bleached nominals in Experiment 3 do not. Taken together with related findings in the literature, these findings favor an account of lexical acquisition in which layers of information become available incrementally, as a consequence of solving prior parts of the learning problem.


Unconscious Processing of Negative Animals and Objects: Role of the Amygdala Revealed by fMRI.
Previous studies have shown that emotional stimuli can be processed through the amygdala without conscious awareness. The amygdala is also involved in processing animate and social information. However, it is unclear whether different categories of pictures (e.g., animals, objects) elicit different activity in the amygdale and other regions without conscious awareness. The objective of this study was to explore whether the factors of category, emotion and picture context modulate brain activation for unconscious processing. Pictures denoting different nonhuman animals and objects in negative and neutral emotional valences were presented using a sandwich-masking paradigm. Half of them were presented with human-related information in the contexts, and half were not. Our results showed significant interaction among category, emotion and context in the amygdala and subcortical regions. Specifically, negative animals elicited stronger activation in these regions than negative objects, especially with human contexts. In addition, there were different correlation patterns between the amygdala and cortical regions according to whether they included human context. There were limited activations in cortical category-related networks. These results suggest that the amygdala and subcortical regions dominantly process negative animals, and contextual information modulates their activities, making threatening stimuli that are most relevant to human survival preferentially processed without conscious awareness.


[A resected case with lung cancer rapidly progressed to the mediastinum].
A 66-year-old man was revealed an abnormal shadow in the chest roentgenogram. Definitive diagnosis was not obtained by chest CT and bronchofiberscopy. Three months later, the shadow showed a rapid increase. We made a diagnosis of lung cancer by needle biopsy. Extended radical operation for the tumor was performed. The tumor with invasion to the chest wall and the mediastinum was completely resected with reconstruction of the chest wall and SVC. Postoperative pneumonia and respiratory failure were occurred, and patient died four months later.


Evoked and event related coherence of Alzheimer patients manifest differentiation of sensory-cognitive networks.
In previous studies on Alzheimer's patients it was shown that, in frontal and parietal locations, delta and theta responses of AD patients were greatly reduced. The present study analyzed coherence functions in these highly affected frontal and parietal areas. Visual sensory and event related coherences of patients with Alzheimer type dementia (AD) were analyzed comparatively. A total of 38 mild, probable AD subjects (19 untreated, 19 treated with cholinesterase inhibitors) were compared with a group of 19 healthy controls. The sensory evoked coherence and event related target coherences were analyzed for delta (1-3.5 Hz), theta (4-7 Hz), alpha (8-13 Hz), beta (15-30 Hz) and gamma (28-48 Hz) frequency ranges for long-range intra-hemispheric (F(3)-P(3), F(4)-P(4), F(3)-T(5), F(4)-T(6), F(3)-O(1), F(4)-O(2)) electrode pairs. The healthy control group showed significantly higher values of event related coherence in "delta", "theta" and "alpha" bands in comparison to the de novo and medicated AD groups (p<0.01 for the delta, theta and alpha) upon application of a target stimuli. In contrast, almost no changes in event related coherences were observed in beta and gamma frequency bands. Furthermore, no differences were recorded between healthy and AD groups upon application of simple light stimuli. Besides this, coherence values upon application of target stimuli were higher than sensory evoked coherence in all groups and in all frequency bands (p<0.01). The cognitive networks of AD patients were highly impaired in comparison to networks activated by sensory stimulation, thus showing separate activation of sensory and cognitive networks.


Broken Rotor Bar Detection in Induction Motors through Contrast Estimation.
Induction motors (IM) are key components of any industrial process; hence, it is important to carry out continuous monitoring to detect incipient faults in them in order to avoid interruptions on production lines. Broken rotor bars (BRBs), which are among the most regular and most complex to detect faults, have attracted the attention of many researchers, who are searching for reliable methods to recognize this condition with high certainty. Most proposed techniques in the literature are applied during the IM startup transient, making it necessary to develop more efficient fault detection techniques able to carry out fault identification during the IM steady state. In this work, a novel methodology based on motor current signal analysis and contrast estimation is introduced for BRB detection. It is worth noting that contrast has mainly been used in image processing for analyzing texture, and, to the best of the authors' knowledge, it has never been used for diagnosing the operative condition of an induction motor. Experimental results from applying the approach put forward validate Unser and Tamura contrast definitions as useful indicators for identifying and classifying an IM operational condition as healthy, one broken bar (1BB), or two broken bars (2BB), with high certainty during its steady state.


Physical localization of the 18S-5.8S-26S rDNA and sequence analysis of ITS regions in Thinopyrum ponticum (Poaceae: Triticeae): implications for concerted evolution.
Fluorescence in situ hybridization was used in Thinopyrum ponticum, a decaploid species, and its related diploid species, to investigate the distribution of the 18S-5.8S-26S rDNA. The distribution of rDNA was similar in all three diploid species (Th. bessarabicum, Th. elongatum and Pseudoroegneria stipifolia). Two pairs of loci were observed in each somatic cell at metaphase and interphase. One pair was located near the terminal end and the other in the interstitial regions of the short arms of one pair of chromosomes. However, all of the major loci in Th. ponticum were located on the terminal end of the short arms of chromosomes, and one chromosome had only one major locus. The maximum number of major loci detected on metaphase spreads was 20, which was the sum of that of its progenitors. The interstitial loci that exist in the possible diploid genome donor species were probably 'lost' during the evolutionary process of the decaploid species. A number of minor loci were also detected on whole regions of two pairs of homologous chromosomes. These results suggested that the position of rDNA loci in the Triticeae might be changeable rather than fixed. Positional changes of 18S-5.8S-26S rDNA loci between Th. ponticum and its candidate genome donors indicate that it is almost impossible to find a genome in the polyploid species that is completely identical to that of its diploid donors. The possible evolutionary significance of the distribution of the rDNA is also discussed. Internal transcribed spacer (ITS) regions of nuclear DNA in Th. ponticum were investigated by PCR amplification and sequencing. The sequence data from five positive clones selected at random, together with restriction site analysis, indicated that the ITS repeated units are nearly homogeneous in this autoallodecapolypoid species. Combined with in situ hybridization results, the data led to the conclusion that the ITS region has experienced interlocus as well as intralocus concerted evolution. Phylogenetic analyses showed that the sequences from Th. ponticum have concerted to the E genome repeat type.


Economic evaluation of a vision-based patient monitoring and management system in addition to standard care for adults admitted to psychiatric intensive care units in England.
Treating patients in psychiatric intensive care units (PICUs) is costly for the English National Health Service (NHS), requiring significant staff time. Oxevision, a non-contact system, providing vision-based patient monitoring and management (VBPMM) has been introduced in some NHS mental health trusts which aims to help clinicians to deliver safer and more efficient care. The objective of this early economic evaluation was to explore the impact of introducing VBPMM with standard care, versus standard care alone on health and economic outcomes in PICUs across England. The model uses a cost calculator approach to evaluate the potential benefits of introducing VBPMM, capturing differences in observation hours and critical events such as assaults. Effectiveness data were primarily based on a 24-month observational before and after study undertaken in an NHS mental health trust using VBPMM. Outcomes reported in this study are incremental costs and reduction in clinical events presented as per occupied bed days, per patient, per average ward, and for the English NHS overall. Scenario analysis was conducted to test the uncertainty of results using statistical significance of key inputs. The analysis indicates that introducing VBPMM may be cost saving compared with standard care alone. The biggest driver of estimated cost savings was from the potential reduction in one to one observation hours, which may have significant impact in PICUs. Limitations of the analysis include the single center data underpinning the analysis and assumptions made about transferability of clinical data to different sized wards. Scenario analysis was conducted, and the results were robust to statistically significant changes in input parameters. This study suggests that introducing VBPMM on PICUs has the potential to reduce costs and improve efficiency of resource allocation, but results should be confirmed with additional clinical study evidence.


[Metazosin tablets (Kenosin) in the treatment of chronic congestive heart failure].
Postsynaptic alpha 1 adrenoceptor blockers are considered suitable drugs for modern vasodilatatory treatment of chronic heart failure. Therefore new analogues of these substances with more favourable characteristics than those of their main representative, prazosin are sought. The objective of the present work was to evaluate the therapeutic effect and tolerance of the original alpha 1-adrenoceptor blocker metazosin developed in the Research Institute for Pharmacy and Biochemistry (VUFB). In a multicentre clinical trial metazosin (tablets à 10 mg), 10-20 mg/day, were added to standard treatment of 56 patients of both sexes suffering from chronic congestive heart failure, for a period of eight weeks. The administration of metazosin led to rapid improvement of subjective complaints (in particular dyspnoea) as well as objective symptoms of peripheral congestion, to a significant (p < 0.05) regression of X-ray signs of pulmonary congestion and a slight (but statistically significant--p < 0.05) increase of the ejection fraction and cardiac output. After two months treatment the functional degree of severity of insufficiency according to the NYHA classification decreased from 2.7 to 2.2. Metazosin did not induce tachycardia and was well tolerated by the patients. Metazosin (Kenosin) tablets is a suitable supporting drug in the comprehensive treatment of chronic cardiac failure, in particular if refractory to treatment.


Electron microscopic observations of the effects of gossypol on the human endometrium.
Gossypol treatment of endometriosis and uterine myomas in 15 cases was started with a daily dose of 20 mg of gossypol-acetic acid twice a day for 20 days as a loading dose, followed by 40 mg (20 mg twice weekly). A maintenance dose of 20 mg was given weekly. The total course of treatment lasted about 6 months. Light and electron microscopic examination of the endometrium was carried out before treatment and 2, 3, 4, and 6 months after gossypol treatment. After gossypol treatment three different characteristics of the endometrium were noted: (1) irregular secretory activity, (2) proliferative activity, and (3) atrophy. On electron microscopic examination it was shown that there were important changes of the organelles, indicating suppressed secretory activity. Based on the above results, the nature and significance of the ultrastructural changes of the endometrium induced by gossypol were analyzed and the possibility of developing a new field of research in female contraception with gossypol was considered.


Energy Intake of Men With Excess Weight During Normobaric Hypoxic Confinement.
Due to the observations of weight loss at high altitude, normobaric hypoxia has been considered as a method of weight loss in obese individuals. With this regard, the aim of the present study was to determine the effect of hypoxia per se on metabolism in men with excess weight. Eight men living with excess weight (125.0 ± 17.7 kg; 30.5 ± 11.1 years, BMI: 37.6 ± 6.2 kg⋅m-2) participated in a randomized cross-over study comprising two 10-day confinements: normobaric (altitude of facility ≃ 940 m) normoxia (NORMOXIA; P I O2 = 133 mmHg), and normobaric hypoxia (HYPOXIA). The P I O2 in the latter was reduced from 105 (simulated altitude of 2,800 m) to 98 mmHg (simulated altitude of 3,400 m over 10 days. Before, and at the end of each confinement, participants completed a meal tolerance test (MTT). Resting energy expenditure (REE), circulating glucose, GLP-1, insulin, catecholamines, ghrelin, peptide-YY (PYY), leptin, gastro-intestinal blood flow, and appetite sensations were measured in fasted and postprandial states. Fasting REE increased after HYPOXIA (+358.0 ± 49.3 kcal⋅day-1, p = 0.03), but not after NORMOXIA (-33.1 ± 17.6 kcal⋅day-1). Postprandial REE was also significantly increased after HYPOXIA (p ≤ 0.05), as was the level of PYY. Furthermore, a tendency for decreased energy intake was concomitant with a significant body weight reduction after HYPOXIA (-0.7 ± 0.2 kg) compared to NORMOXIA (+1.0 ± 0.2 kg). The HYPOXIA trial increased the metabolic requirements, with a tendency toward decreased energy intake concomitant with increased PYY levels supporting the notion of a hypoxia-induced appetite inhibition, that could potentially lead to body weight reduction. The greater postprandial blood-glucose response following hypoxic confinement, suggests the potential development of insulin resistance.


An international multicenter randomized controlled trial of G17DT in patients with pancreatic cancer.
This study aimed to investigate G17DT, an immunogen producing neutralizing antibodies against the tumor growth factors amidated and glycine-extended forms of gastrin-17, in the treatment of pancreatic cancer. A randomized, double-blind, placebo-controlled, group-sequential multicenter trial of G17DT in patients with advanced pancreatic cancer unsuitable for or unwilling to take chemotherapy. Inclusion criteria were a Karnofsky performance score of 60 or higher and a life expectancy of more than 2 months. Patients received G17DT or placebo emulsion at weeks 0, 1, 3, 24, and 52. The primary end point was survival, and secondary end points were tolerability, Karnofsky performance. A total of 154 patients were recruited: 79 G17DT and 75 placebo. A final analysis of the intention-to-treat population, using a proportional hazards model, stratifying by disease stage and adjusting for interim analysis, gave a hazard ratio for mortality of 0.75 (95% confidence interval, 0.51-1.10, P = 0.138; G17DT/placebo). A conventional analysis without adjustment for disease stage or interim analysis, censoring for chemotherapy and excluding protocol violators, gave median survival periods of 151 (G17DT) and 82 days (placebo) (log-rank test, P = 0.03).Patients developing anti-G17DT responses (73.8%) survived longer than nonresponders or those on placebo (median survival, 176 vs 63 vs 83; log-rank test, P = 0.003). G17DT was well tolerated.


[Cysteine lithiasis].
Cystinuria is a common inherited amino-aciduria resulting in abnormal urinary excretion of cystine and the dibasic aminoacids, lysine, arginine and ornithine. Formation of cystine kidney stones, recurrent infections and subsequent renal failure are the main complications of the disease. Recently, the gene SLC3A1 and SLC7A9, encoding the two subunits rBAT et b0,+AT of the proximal renal transporter complex, have been identified. In this article, we report the medical history of a 30-year-old patient and discuss the recent molecular progress, the clinical evolution, and the medical treatment of the cystinuria.


Testing tic suppression: comparing the effects of dexmethylphenidate to no medication in children and adolescents with attention-deficit/hyperactivity disorder and Tourette's disorder.
The aim of this study was to conduct a pilot study testing whether single-dose, immediate-release dexmethylphenidate (dMPH) can facilitate tic suppression in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and Tourette's disorder (TD) or chronic tic disorders. The primary hypothesis is that dMPH will improve behaviorally reinforced tic suppression in a standard tic suppression paradigm (TSP). Ten children with ADHD and TD were given dMPH on one visit and no medication on another, using a random crossover design. On both days, following a baseline period, subjects were reinforced for suppressing tics using a standard TSP. Thirteen subjects were enrolled; 10 subjects (mean age 12.7 +/- 2.6; 90% male) completed all study procedures. Relative to the no-medication condition, tics were reduced when children were given a single dose of dMPH. Behavioral reinforcement of tic suppression resulted in lower rates of tics compared to baseline, but dMPH did not enhance this suppression. Preliminary results indicate replication of prior studies of behavioral tic suppression in youths with TD and without ADHD. In addition, our findings indicate tic reduction (and not tic exacerbation) with acute dMPH challenge in children and adolescents with ADHD and TD.