The effect of Ge, Si and Sn phthalocyanine photosensitizers on cell proliferation and viability of human oesophageal carcinoma cells.
The photodynamic activity of water soluble mixed sulfonated metallophthalocyanines complexes: GePcSmix, SnPcSmix and SiPcSmix on human oesophageal carcinoma (SNO) cells are reported, and compared with the activity of the unmetallated H2PcSmix and of the newly synthesized water soluble adjacently substituted binaphthalo phthalocyanine (complex 3). The alkaline phosphate (ALP) showed damage to the cell membrane in the presence of complex 3 without irradiation. The GePcSmix complex caused a relatively large increase in inflammation and a high intracellular ATP.


Cumulus cells of camel (Camelus dromedarius) antral follicles are multipotent stem cells.
The mammalian ovary is a highly dynamic organ, in which proliferation and differentiation occur constantly during the entire life span, particularly in camels that are characterized by a follicular wave pattern and induced ovulation. Granulosa cells are the main cells of mature follicles. Two distinct cell types, namely, the mural and cumulus granulosa cells are distinguished on the basis of antral fluid increase. The multipotency of follicular fluid and the luteinizing cell were recently demonstrated. However, reports regarding the plasticity of cumulus cells are lacking. We obtained cumulus cells from cumulus-oocyte complexes and showed that camel cumulus cells expressed stem cell mRNA transcripts (POU5A1, KLF4, SOX2, and MYC) and were able to differentiate into other non-ovarian follicular cell types in vitro, such as neurons, osteoblasts, and adipocytes. In contrast, removal of the ooplasm (oocytectemy) showed no effect on cumulus cell proliferation and differentiation. This is the first report to identify an invaluable source of multipotent stem cells, which is routinely discarded during in vitro embryo production. The plasticity and transdifferentiation capability of camel cumulus cells definitely requires attention as it provides a cheap biological experimental model for basic research in stem cells and for understanding ovarian differentiation, both of which are relevant for use in regenerative medicine and tissue engineering in humans and animals.


Risk factors for coronary heart disease in diabetic and nondiabetic Native Americans. The Strong Heart Study.
The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35-74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45-74 during the same time. In addition, a physical examination was performed on persons 45-74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors. In Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.


The OptiLUTS trial: improving care for therapy-resistant symptoms of the pelvis in Belgium.
Introduction/Background: The management of therapy-resistant lower urinary tract symptoms (LUTS) and symptoms resulting from pelvic organ dysfunctions are subject to a high variability in the Belgian health-care centres. Practical guidelines and standardized patient clinical care pathways are often lacking and unadapted to the Belgian healthcare system. Objectives: The OptiLUTS trial aims to improve the multidisciplinary care of therapy-resistant symptoms of the pelvis in the Belgian healthcare setting. Project A aims for the improvement of knowledge of 2nd line treatments for LUTS among general practitioners. In project B a treatment algorithm for the overactive bladder syndrome and non-obstructive urinary retention will be developed specifically for Belgium. In Project C a patient customized sacral neuromodulation (SNM) care pathway will be set up. Methods: Part A: Explorative study among general practitioners by distribution of a questionnaire. Part B: Review of existing guidelines and use of the Delphi method to obtain expert consensus. Part C: A single center comparative study to compare outcomes before and after implementation of the SNM care pathway. Patients scheduled for the first stage of Interstim therapy™ will be included (N=100). Primary endpoints are the sensitivity and specificity of a new pelvic symptom assessment tool, the conversion to implant and explantation rates. Conclusion: There is a margin for improvement in the care process of patients with therapy-resistant symptoms of the pelvis in the Belgium healthcare system. In the OptiLUTs trial adapted guidelines and a clinical care pathway will be developed to standardize and increase the efficiency of care. Trial registration: Approval for the trial by the Ethics Committee of the Ghent University hospital: EC/2018/0244.


[Action of actidion on the replication of the transmissible gastroenteritis virus].
Explored was the possibility of inhibiting the replication of the virus of the transmissive gastroenteritis by means of actidione. It was found that in certain concentrations the antibiotic completely inhibited the replication of this virus. In individual strains the process of replication was not influenced by the various concentrations applied. It was demonstrated that when the antibiotic was added to the infected cell cultures during individual phases its varying concentrations influenced the virus replication. When actidione was added to the cells at the time of virus adsorption it did not inhibit the synthesis of the virus. Similar were the results when the cells were cultivated 24 hours with specified concentrations of actidione prior to their infection with the virus.


A large urban outbreak of histoplasmosis: clinical features.
An outbreak of histoplasmosis estimated to involve more than 100,000 residents in Indianapolis, Indiana, occurred between September 1978 and August 1979. In the 435 cases evaluated, 52% of the patients were between 15 and 34 years old, and 63% were black. Fifteen patients died, and 46 progressive disseminated infection. Twenty-four patients had pericarditis, and 26 had rheumatologic syndromes. Unusual manifestations that occurred in 18 patients included esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. The highest attack rate was in the central part of the city, which is a densely populated, disproportionately black section. The source of the outbreak has not been proved by positive culture results; two sites, however, were suspected on an epidemiologic basis.


Identification of a shrimp-derived allergen as tRNA.
During an attempt to isolate shrimp allergens, evidence was obtained that shrimp ribonucleic acid was capable of eliciting a specific IgE response in man and an experimental animal model system. The shrimp ribonucleic acid was extracted from boiled whole shrimp (Peneaus indicus), and was isolated by salt precipitation and sequential chromatography over DEAE-Sephacel and BioGel P-100. The allergenic material was identified as a ribonucleic acid based on the following criteria: a maximal absorption at 258 nm, failure to stain positively with Coomassie Brilliant Blue on slab gel electrophoresis, positive staining with ethidium bromide, co-migration with yeast tRNA on submerged gel electrophoresis in 1.5% Agarose M, and sensitivity to ribonuclease T2 and 0.3 M NaOH. Treatment with protease did not alter its allergenic activity. The RNA was capable of binding allergen-specific IgE in sera from two shrimp-sensitive patients, as demonstrated by microELISA and solid-phase radioimmunoassay (SPRIA) using antigen-coated nitrocellulose filter paper discs and purified 125I-labeled goat anti-human IgE. RNA isolated from shrimp by a conventional tRNA isolation procedure also had the ability to specifically bind IgE in the sera of shrimp-sensitive patients. IgE antibodies to shrimp RNA did not recognize yeast tRNA or salmon testes DNA, and were not detected in sera of other subjects. The shrimp-derived RNA was further able to induce a reaginic response in mice. A combination of in vitro aminoacylation of shrimp tRNA and SPRIA resulted in the identification of the allergenic tRNA as tRNA(Tyr) and tRNA(Arg). Thus, shrimp tRNA is capable of inducing a specific IgE response in man.


Novel 4-phenoxy-2-(1-piperazinyl)quinazolines as potent anticonvulsive and antihypoxic agents.
A series of 4-phenoxy-2-(1-piperazinyl)quinazolines was synthesized and examined for anticonvulsive and antihypoxic activities. Many of the compounds exhibited potent anticonvulsive activity comparable to that of carbamazepine or phenytoin. Among them, 4-phenoxy-2-(4-propyl-1-piperazinyl)quinazoline (5w) was selected as the most promising candidate antiepileptic drug with few side effects. It seemed that potent anticonvulsive activity was a prerequisite for potent antihypoxic activity.


[Expression of mRNA of osteocalcin in condylar cartilage of young SD rats after functional protrusion].
To study the temporal and spatial patterns of the expression of mRNA in condylar cartilage of young growing SD rats, in condition of different functional treatment time span. SD rats are randomly divided into 3 groups: control, all-day group (wearing functional appliance for 24 hours a day) and 12-hour group (wearing appliance for 12 hours in daytime). After one week, animals are sacrificed and Osteocalcin mRNA expression is studied by in situ hybridization using Oligonucleotide probe, calculated by image processing and macroscopic and microscopic statistics. Osteocalcin mRNA is expressed in condylar cartilage of young growing SD rats and the acrophase is around 6:00 am. After wearing the functional appliance, the intensity in all-day group rises more than that in 12-hourgroup. Better results can be achieved in all-day group with functional appliance.


Perceptual distance and the moon illusion.
The elevated moon usually appears smaller than the horizon moon of equal angular size. This is the moon illusion. Distance cues may enable the perceptual system to place the horizon moon at an effectively greater distance than the elevated moon, thus making it appear as larger. This explanation is related to the size-distance invariance hypothesis. However, the larger horizon moon is usually judged as closer than the smaller zenith moon. A bias to expect an apparently large object to be closer than a smaller object may account for this conflict. We designed experiments to determine if unbiased sensitivity to illusory differences in the size and distance of the moon (as measured by d') is consistent with SDIH. A moon above a 'terrain' was compared in both distance and size to an infinitely distant moon in empty space (the reduction moon). At a short distance the terrain moon was adjudged as both closer and smaller than the reduction moon. But these differences could not be detected at somewhat greater distances. At still greater distances the terrain moon was perceived as both more distant and larger than the reduction moon. The distances at which these transitions occurred were essentially the same for both distance and size discrimination tasks, thus supporting SDIH.


Cost-effectiveness simulation analysis of schizophrenia at the Instituto Mexicano del Seguro Social: Assessment of typical and atypical antipsychotics.
Estimation of the economic costs of schizophrenia is a fundamental tool for a better understanding of the magnitude of this health problem. The aim of this study was to estimate the costs and effectiveness of five antipsychotic treatments (ziprasidone, olanzapine, risperidone, haloperidol and clozapine), which are included in the national formulary at the Instituto Mexicano del Seguro Social, through a simulation model. Type of economic evaluation: complete economic evaluation of cost-effectiveness. direct medical costs. 1 year. Effectiveness measure: number of months free of psychotic symptoms. to estimate cost-effectiveness, a Markov model was constructed and a Monte Carlo simulation was carried out. Effectiveness: the results of the Markov model showed that the antipsychotic with the highest number months free of psychotic symptoms was ziprasidone (mean 9.2 months). The median annual costs for patients using ziprasidone included in the hypothetical cohort was 194,766.6 Mexican pesos (MXP) (95% CI, 26,515.6-363,017.6 MXP), with an exchange rate of 1 € = 17.36 MXP. The highest costs in the probabilistic analysis were estimated for clozapine treatment (260,236.9 MXP). Through a probabilistic analysis, ziprasidone showed the lowest costs and the highest number of months free of psychotic symptoms and was also the most costeffective antipsychotic observed in acceptability curves and net monetary benefits.


Bone-graft augmentation for acetabular deficiencies in total hip arthroplasty. Results of long-term follow-up evaluation.
The results of 102 consecutive primary and revision total hip arthroplasties performed with bone-grafting for acetabular bone deficiencies were reviewed at an average of 10.2 years (range, 4-18.6) after surgery. Ninety-one percent had structural bone defects and 57% had underlying developmental dysplasia of the hip. Overall acetabular revision rates for aseptic loosening were 8% at 5 years and 26% at 10 years. In addition, in the patients with developmental dysplasia who had primary hip arthroplasties, acetabular revision rates for aseptic loosening were 3 and 18% at 5 and 10 years, respectively. Ninety-six percent of all uninfected grafts incorporated. Bulk grafts fared better than particulate grafts. No difference in failure rate was noted between primary and revision hip arthroplasty, type of deficiency, or amount of graft coverage. Although early results are encouraging, acetabular failure increased significantly with longer follow-up evaluation; however, graft incorporation was successful and facilitated subsequent revision surgery.


Randomized controlled trial to assess the impact of continuous glucose monitoring on HbA(1c) in insulin-treated diabetes (MITRE Study).
To determine whether continuous glucose information provided through use of either the GlucoWatch G2 Biographer or the MiniMed continuous glucose monitoring system (CGMS) results in improved glycated haemoglobin (HbA(1c)) for insulin-treated adults with diabetes mellitus, relative to an attention control and standard care group. Four hundred and four adults taking at least two daily insulin injections and with two consecutive HbA(1c) values > or = 7.5% were recruited to this randomized controlled trial (RCT). All were trained at baseline to use the same monitor for traditional capillary glucose testing throughout the 18-month study. The CGMS group were asked to wear the device three times during the first 3 months of the trial and on another three occasions thereafter. The GlucoWatch group wore the device a minimum of four times per month and a maximum of four times per week during the first 3 months and as desired for the remainder of the trial. Trained diabetes research nurses used downloaded data to guide therapy adjustments. Proportional reduction in HbA(1c) from baseline to 18 months was the primary outcome measure. Neither an intention-to-treat nor per-protocol analysis showed improvement in HbA(1c) in the device groups compared with standard care. For the intention-to-treat analysis, when the standard care group was compared with each of the other groups, this equated to differences in mean relative HbA(1c) reduction (95% confidence interval) from baseline to 18 months of 3.5% (-1.3 to 8.3; GlucoWatch), 0.7% (-4.1 to 5.5; CGMS), and -0.1% (-4.6 to 4.3; attention control). The additional information provided by these devices did not result in improvements in HbA(1c) in this population.


Purification and properties of human serum carnosinase.
Carnosinase from human plasma was purified 18,000-fold to apparent homogeneity in a four step procedure. The dipeptidase was partially inactivated during DEAE-cellulose chromatography; however, it reactivated slowly when concentrated and stored at 4 degrees C. In the second purification step, hydroxylapatite column chromatography, two forms of the enzyme were separated from one another. Human serum carnosinase was found to be a glycoprotein with a pI of 4.4 and a subunit Mr of 75,000; the active enzyme was a dimer, the two subunits being connected by one or more disulfide bonds. The enzyme was especially active in hydrolyzing carnosine and anserine, preferring dipeptides with histidine in the C-terminal position. In most human tissues, the concentration of serum carnosinase was proportional to the percentage of trapped blood in the sample. However, the brain contained about 9 times more enzyme than expected, based on the amount of trapped blood present. The physiological function of this enzyme seems to be the hydrolysis of homocarnosine in the brain and the splitting of carnosine and anserine in the blood stream. Six higher primates were found to have serum carnosinase. Twelve nonprimate mammals were tested; all were lacking the serum enzyme except for the Golden hamster, which had very high concentrations of a carnosinase having somewhat different properties than the higher primate enzyme.


Relevance of DNA damage repair in the management of prostate cancer.
Recent insights into the genomic aberrations that underlie and drive prostate cancer have redoubled efforts to molecularly stratify treatments based on predictive markers. Approximately 23% of patients with metastatic castration-resistant prostate cancer exhibit somatic or germline aberrations in genes implicated in DNA repair, such as BRCA2, BRCA1, ATM, CHEK2, and PALB2, as well as mismatch repair genes. At least 10% of men with advanced disease have germline mutations in DNA-repair genes (DRG). The enrichment of DRG defects in metastatic disease compared with localized, primary tumors suggests a possible role in carcinogenesis, disease progression, and potentially accounts for a more aggressive phenotype. Germline BRCA2-mutant prostate cancer is more likely to present with advanced disease, higher Gleason score, and exhibit poorer survival than noncarriers. Very little is currently known about the clinicopathological features of prostate cancer associated with rarer DRG variants. It is currently unknown whether germline carriers of DRG mutations would benefit from additional screening strategies or more intensive treatment of localized prostate cancer. Defective DNA repair may have profound therapeutic implications for advanced disease, conferring tumor-specific vulnerability to poly(ADP-ribose) polymerase inhibitors, platinum chemotherapy, or immunotherapy that can be exploited for clinical benefit. Pertinent issues regarding cancer risk, screening recommendations and risk reduction strategies for carriers of poorly characterized DRG variants remains to be defined. We review the prevalence and potential clinical implications of DNA damage repair defects in prostate cancer. The broader promise and challenge of implementing this knowledge into clinical practice is also discussed.


Feedback of the amygdala globally modulates visual response of primary visual cortex in the cat.
The amygdala is an important center for emotional behavior, and it influences other cortical regions. Long feedback projections from the amygdala to the primary visual cortex were recently reported in the cat and monkey, two animal models for vision research. However, the detailed functional roles of these extensive projections still remain largely unknown. In this study, intrinsic signal optical imaging was used to investigate the visually driven responses of the primary visual cortex of cats as focal drugs were injected into the basal nucleus of the amygdala. Both the visually evoked global signals and differential signals in the functional maps of the primary visual cortex were enhanced or reduced by glutamate-induced activation or GABA-induced deactivation of neurons in the amygdala, respectively. This modulation was found to be non-selective, consistent with the gain control mechanism-both the preferred orientation and its mapped orientation tuning width remained unchanged. The single unit recordings showed similar results supporting the above observations. These results suggest that the distal feedback signals of the amygdala enhance the primary sensory information processing in a non-selective, gain-control fashion. This provides direct neurophysiological evidence and insight for previous studies on emotional-cue related psychological studies.


Araticum (Annona crassiflora Mart.) as a source of nutrients and bioactive compounds for food and non-food purposes: A comprehensive review.
Araticum (Annona crassiflora Mart.) is a fruitful tree native to the Brazilian Cerrado biome that holds high nutritional, functional and economic potential. This plant has been used since ancient times by folk medicine for the treatment of several pathological conditions. There has been increasing interest in the development of pulp-based food products as well as the by-products utilization to obtain value-added ingredients. Understanding the chemical composition and biological activities of different botanical parts of Annona crassiflora Mart. provides a basis to support future researches and applications. In this context, this paper carries out an exhaustive review of the scientific literature, on the main phytochemicals of different botanical parts of Annona crassiflora Mart. (fruit, leaves, stem and root) and their biological activities, assessing their potential uses for several industrial segments. Annona crassiflora Mart. fruits and especially their by-products (peel and seeds) and leaves have been shown a wide range of bioactive compounds such as phenolic compounds, alkaloids, annonaceous acetogenins, tocols, carotenoids, phytosterols, dietary fiber, vitamins, minerals and essential oils. These compounds contribute to various biological activities, including antioxidant, hepatoprotective, anti-inflammatory, antitumoral, analgesic, antidiabetic, skin healing, antidiarrhoeic, antimicrobial, antiparasitic, insecticide and herbicide activities of Annona crassiflora Mart. extracts. Therefore, these findings demonstrate that Annona crassiflora Mart. fruit, by-products and leaves can be excellent candidates to be used as functional foods and/or sources for obtaining bioactive compounds for the food, cosmetics and pharmaceutical applications.


Benign mediastinal teratoma causing pericardial tamponade and pleural effusion.
Mediastinal teratomas are known to adhere to and penetrate the pericardium, but perforation and tamponade are uncommon. We present a patient who developed a life-threatening pericardial tamponade and pleural effusion, whose life was saved by timely surgery. We believe this to be the third successfully treated patient and the first to be reported from Great Britain.


Severe hyponatraemia in a quadriplegic.
A young quadriplegic patient developed convulsions and brain damage due to severe hyponatraemia. Potential causes of severe hyponatraemia in quadriplegics include excessive water intake (because of the low threshold for vasopressin release) and asymptomatic renal tract infection causing sodium loss. Mild hyponatraemia, occurring in up to 10% of quadriplegics, is due to a reset osmostat.


Diffusion of microcystins (cyanobacteria hepatotoxins) from the reservoir of Isahaya Bay, Japan, into the marine and surrounding ecosystems as a result of large-scale drainage.
In the artificial reservoir of the Isahaya reclaimed land, Nagasaki, Japan, algal blooms have become an annual event, dominated primarily by the microcystin (MC) producing cyanobacteria Microcystis aeruginosa. Although the majority of MCs are either degraded by bacteria or washed out to sea, some remain in the sediment of the reservoir and bay throughout the year. As a result, they also accumulate in aquatic organisms (mullet, oyster, etc.) that inhabit the reservoir and surrounding areas, as well as midge flies that spend their larval period in the bottom of the reservoir. Accordingly, MCs also accumulate in the predators of these organisms, allowing the toxin to spread from the hydrosphere to terrestrial ecosystems. The most effective method for resolving this potentially dangerous condition is to introduce seawater into the reservoir by opening the drainage gates at high tide.


Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.
The small GTPase Rap1 and its guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), are critical for platelet function and hemostatic plug formation. CDGI function is regulated by a calcium binding EF hand regulatory domain and an atypical C1 domain with unknown function. Here, we investigated whether the C1 domain controls CDGI subcellular localization, both in vitro and in vivo. CDGI interaction with phosphoinositides was studied by lipid co-sedimentation assays and molecular dynamics (MD) simulations. Cellular localization of CDGI was studied in heterologous cells by immunofluorescence and subcellular fractionation assays. Lipid co-sedimentation studies demonstrated that the CDGI C1 domain associates with membranes through exclusive recognition of phosphoinositides, phosphatidylinositol (4,5)-biphosphate (PIP2) and phosphatidylinositol (3,4,5)-triphosphate (PIP3). MD simulations identified a phospholipid recognition motif consisting of residues exclusive to the CDGI C1 domain. Mutation of those residues abolished co-sedimentation of the C1 domain with lipid vesicles and impaired membrane localization of CDGI in heterologous cells. Our studies identify a novel interaction between an atypical C1 domain and PIP2/PIP3 in cellular membranes, which is critical for Rap1 signaling in health and disease.


Decreased expression of cellular markers in Epstein-Barr virus-positive Hodgkin's disease.
Epstein-Barr virus (EBV) has been demonstrated in the Reed-Sternberg cells and their mononuclear variants (Hodgkin cells; H-RS cells) in a substantial number of Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in vitro the expression of several cellular genes, including lymphoid differentiation markers. Therefore we investigated, in 64 cases of HD, the relationship between the presence of EBV and the expression of lymphoid (CD45RB), T- (CD3, CD45RO), B- (CD20, MB2 antigen, CDw75), and myeloid-cell lineage markers (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H-RS cells. EBV-positive cases, as demonstrated by the presence of EBER-1 and -2 RNA and LMP-1 protein expression, showed a significant reduction in the expression on H-RS cells of T-cell lineage (CD3, P < 0.02), B-cell lineage (CD20; P < 0.005), and activation markers (EMA; P < 0.002 and the 115D8 antigen; P < 0.001) as compared with EBV-negative cases. No differences were found in the expression of CD15, CD30, CD45RO, CD45RB, CDw75, or the MB2 antigen on H-RS cells in EBV-positive and EBV-negative HD cases. Interestingly, in 11 cases of EBV-negative HD, B- as well as T-cell lineage markers could be found on some H-RS cells. These data suggest that EBV in H-RS cells is able to down-regulate the expression of T- (CD3) and B- (CD20) cell lineage markers and lymphoid activation markers (EMA and the 115D8 antigen).(ABSTRACT TRUNCATED AT 250 WORDS)


Lizards at the Peak: Physiological Plasticity Does Not Maintain Performance in Lizards Transplanted to High Altitude.
Warming climates are facilitating the range expansion of many taxa to habitats that were formerly thermally inhospitable, including to higher latitudes and elevations. The potential for such colonization, however, varies widely among taxa. Because environmental factors may interact to affect colonization potential, an understanding of underlying physiological and behavioral mechanisms is necessary to predict how species will respond to potentially suitable habitats. For example, temperature and oxygen availability will interact to shape physiological and performance traits. Our model species, the wall lizard, Podarcis muralis, is a widely distributed ectotherm that continues to expand its range in Europe despite being limited by cold temperatures at high elevations and latitudes. To test the potential for organisms to expand to warming high-altitude environments, we conducted a transplant experiment to quantify the within-individual effects of high-altitude hypoxia on physiological and performance traits. Transplanted lizards maintained individual differences in physiological traits related to oxygen capacity and metabolism (hemoglobin concentration, hematocrit, and peak postexhaustion metabolic rate), as well as performance traits tied to fitness (sprint speed and running endurance). Although lizards altered blood biochemistry to increase oxygen-carrying capacity, their performance was reduced at high altitude. Furthermore, lizards at high altitude suffered a rapid loss of body condition over the 6-wk experiment, suggesting an energetic cost to hypoxia. Taken together, this demonstrates a limited potential for within-individual plasticity to facilitate colonization of novel high-altitude environments.


Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28.
The structure of human CTLA-4 reveals that residues Met 99, Tyr 100 and Tyr 104 of the M99YPPPY104 motif are adjacent to a patch of charged surface residues on the A'GFCC' face of the protein. Mutation of these residues, which are conserved in the CTLA-4/CD28 family, significantly reduces binding to CD80 and/or CD86, implicating this patch as a ligand binding site.


Target and afferents interact to control developmental cell death in the mesencephalic parabigeminal nucleus of the rat.
During the period of natural cell death in the developing mammalian brain, both target cells and afferents have been shown to be important for neuronal survival. Here we demonstrate that afferents and targets have interactive roles in the maintenance of cells during development of the mesencephalic parabigeminal nucleus (PB) in rats. Pyknotic nuclei were counted in the PB of developing rats that received a bilateral lesion of the superior colliculus on the day of birth (P0). We observed that simultaneous deafferentation and deeferentation leads to a large peak of cell death at P1-2 in all three divisions of PB. Later the rate of pyknosis decreases and a second period of elevated cell death is observed just before the complete disappearance of the nucleus at P7-8. Counts of healthy neurones indicates two separate periods of increased neuronal loss. The first period occurs at P1-2, and the last and dramatic episode of cell loss at P8 leads to the disappearance of the PB. The combined effects of simultaneous target removal and deafferentation were different from the sum of the individual effects, indicating that the axonal targets and the afferents interact to control cell survival in the PB.


[Screening with meaning? Use of ultrasound in pregnancy].
Norway introduced an offer of one routine ultrasound examination to all pregnant women in 1986. Since then, an improved ultrasound technology and more skillful operators have made it possible to detect foetal malformations at a much higher rate. A new consensus conference on the use of diagnostic ultrasound during pregnancy will be held in Norway in 1995. The present paper reviews the recent literature on ultrasound screening. Three randomized controlled trials (the Uppsala-trial from 1988, the Helsinki-trial from 1990, and the RADIUS-trial from 1993) and one meta-analysis (Bucher and Scmidt, 1993) are evaluated. The author also comments on the recent epidemiological studies on the safety aspects of routine ultrasonography during pregnancy.


Mode-controlled colors from microstructure fibers.
We experimentally demonstrate mode-controlled spectral transformation of femtosecond laser pulses in microstructure fibers. Depending on the waveguide mode excited in the fiber, 30-fs Ti: sapphire laser pulses can either generate a broadband emission or produce isolated spectral components in the spectrum of output radiation. This method is used to tune the frequencies dominating the output spectra, controlled by phase matching for four-wave mixing processes.


Manipulation of estrogen synthesis alters MIR202* expression in embryonic chicken gonads.
Tissue-specific patterns of microRNA (miRNA) expression contribute to organogenesis during embryonic development. Using the embryonic chicken gonads as a model for vertebrate gonadogenesis, we previously reported that miRNAs are expressed in a sexually dimorphic manner during gonadal sex differentiation. Being male biased, we hypothesised that up-regulation of microRNA 202* (MIR202*) is characteristic of testicular differentiation. To address this hypothesis, we used estrogen modulation to induce gonadal sex reversal in embryonic chicken gonads and analyzed changes in MIR202* expression. In ovo injection of estradiol-17beta at Embryonic Day 4.5 (E4.5) caused feminization of male gonads at E9.5 and reduced MIR202* expression to female levels. Female gonads treated at E3.5 with an aromatase inhibitor, which blocks estrogen synthesis, were masculinized by E9.5, and MIR202* expression was increased. Reduced MIR202* expression correlated with reduced expression of the testis-associated genes DMRT1 and SOX9, and up-regulation of ovary-associated genes FOXL2 and CYP19A1 (aromatase). Increased MIR202* expression correlated with down-regulation of FOXL2 and aromatase and up-regulation of DMRT1 and SOX9. These results confirm that up-regulation of MIR202* coincides with testicular differentiation in embryonic chicken gonads.


Longitudinal analysis of the association between depressive symptomatology and cognitive deterioration.
Although many studies have found a cross-sectional relation between depression and dementia or depressive symptomatology and cognitive functioning, the direction of the association is still unknown. The purpose of this analysis was to determine whether high depressive symptomatology is predictive of cognitive deterioration among the elderly 3 years later. Data came from a community-based prospective cohort study of noninstitutionalized and nondemented subjects aged 65 years and over living in the Gironde department in southwest France (1,600 subjects were interviewed at both study entry in 1989 and 3-year follow-up). Cognitive functions were assessed with the Mini-Mental State Examination (MMSE), and cognitive deterioration was defined as an MMSE score decrease of at least five points between two assessments. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to evaluate the level of depressive symptomatology. The present study reports that a high level of depressive symptomatology is not predictive of cognitive deterioration 3 years later (relative risk = 0.8, 95% confidence interval 0.3-2.1). The authors observed that the risk of cognitive deterioration was associated with the concomitant level of depressive symptomatology at the 3-year follow-up, independent of depressive symptoms at entry. These results indicate that the association between high depressive symptomatology and poor cognitive functioning is cross-sectional, and they illustrate the importance of adjusting for depressive symptomatology in epidemiologic studies assessing cognitive functions.


Multidisciplinary management of locally advanced and widely metastatic paraganglioma in a patient with life-threatening compressive symptoms.
Patients presenting with locally advanced, metastatic paraganglioma with life-threatening compressive symptoms of critical anatomic structure pose a significant management challenge. We present a case of a 15-year-old patient with enlarging right neck mass causing dysphagia and respiratory compromise from near complete obstruction of the oropharynx. Evaluation of the patient's family history led to the identification of a mutation in the succinate dehydrogenase subunit B (SDSD) gene (G725A). Laboratory and imaging workup revealed an 8.8 × 6.6 × 4.1 cm metabolically and biochemically active right neck mass, a tumor in the left para-aortic region, and multiple bony lesions consistent with widely metastatic disease. Multidisciplinary management included preoperative clinical optimization, coil embolization, and palliative resection of the neck mass. Although the currently available treatment options for patients with advanced metastatic paraganglioma render no survival benefit, a multidisciplinary management approach aimed at relief of tumor-related symptoms and catecholamine excess should be undertaken.


Behaviour of thyroid tissue from patients with Graves' disease in nude mice.
Thyroid tissue from five patients with hyperthyroidism due to Graves' disease was transplanted into nu/nu mice (2 to 4 mice per thyroid) in order to assess whether the tissues would remain hyperfunctional. Before surgery, the patients received only propranolol and iodine for ten days. Transplants were removed from the mice after 10, 20, 30 or 57 days, and compared to the initial tissue, as well as toxic nodules from two patients and thyroid tissue from two normal subjects grafted similarly. All transplants survived, as proven by histology and autohistoradiography with 131I uptake, while all signs of hyperfunction and dysimmunity disappeared. Conversely, both transplanted toxic nodules remained hyperfunctional. These results indicate that, in spite of the in situ presence of most factors of auto-immune reactions, thyroid tissue from patients with Graves' disease is not autonomous and depends on the extra-thyroid environment.


In vivo and in vitro synthesis of the spore-specific proteins A and C of bacillus megaterium.
Pulse labeling of cells of Bacillus megaterium followed by cell disruption and immunoprecipitation has shown that the spore-specific Proteins A and C are synthetized only during a discrete time period in sporulation. At its maximum, the synthesis of the A- and C-proteins accounted for 5% of the protein being synthesized in vivo, but the mRNA for the A- and C-proteins had a lifetime no longer than that of other mRNAs translated at that time. No evidence was found for synthesis of Proteins A or C in high molecular weight precursor form, and essentially all of the newly synthesized A- and C-protein was found in the forespore. Isolation of total RNA from cells in various stages of growth and sporulation, translation of this RNA in a cell-free system from vegetative cells, and immunoprecipitation showed that the ability of cellular RNA to promote A- and C-protein synthesis in vitro was directly proportional to the rate at which the cells had been synthesizing Proteins A and C in vivo. These data indicate that synthesis of Proteins A and C during sporulation in B. megaterium is primarily under transcriptional control. The identity of the immunoprecipitated labeled material material synthesized in vitro with the A- and C-proteins was established by: 1) their co-migration on sodium dodecyl sulfate-polyacrylamide gels; 2) co-migration on high performance liquid chromatography of tryptic peptides from an [35S]methionine-labeled immunoprecipitate with the methionine-containing tryptic peptides of the A- and C-proteins; and 3) digestion of the labeled immunoprecipitate with a protease specific for the A- and C-proteins.


Ultraviolet irradiation alters transforming growth factor beta/smad pathway in human skin in vivo.
Solar ultraviolet irradiation damages human skin and causes premature skin aging and skin cancer. As transforming growth factor beta plays an important role in regulating cell growth and extracellular matrix synthesis, we investigated expression of transforming growth factor beta isoforms, transforming growth factor beta receptors, and transforming growth factor beta regulated Smad transcription factors following irradiation with an ultraviolet B source and solar-simulated ultraviolet irradiation of human skin in vivo. Full-thickness, sun-protected adult human skin expressed transforming growth factor beta1, beta2, and beta3 transcripts in a ratio of 1:5:3, as determined by quantitative real-time reverse transcription polymerase chain reaction. Northern analysis demonstrated that the ultraviolet irradiation (2 minimal erythema dose) caused moderate (2-3-fold) gradual increases of transforming growth factor beta1 and beta3 mRNA expression during 3 d post exposure. In contrast, expression of transforming growth factor beta2 mRNA, the predominant form of transforming growth factor beta in human skin, decreased within 4 h after ultraviolet irradiation. In situ hybridization revealed transforming growth factor beta1, beta2, and beta3 mRNA expression in cells throughout the epidermis and the dermis in nonirradiated skin. Following ultraviolet or solar-simulated ultraviolet irradiation, transforming growth factor beta1 and beta3 mRNA were increased and transforming growth factor beta2 mRNA was reduced throughout the epidermis and dermis. No significant changes were observed in transforming growth factor beta type I receptor mRNA expression after ultraviolet irradiation. In contrast, transforming growth factor beta type II receptor mRNA expression was reduced 60% within 4 h following ultraviolet exposure in human skin in vivo. Transforming growth factor beta type II receptor mRNA levels remained reduced for 8 h and recovered by 24 h post ultraviolet. In situ hybridization revealed that ultraviolet or solar-simulated ultraviolet irradiation caused loss of transforming growth factor beta type II receptor mRNA in basal and suprabasal cells in the epidermis and dermal cells. In addition, no significant changes were observed in Smad2, Smad3, and Smad4 expression after ultraviolet irradiation. In contrast, ultraviolet and solar-simulated ultraviolet irradiation rapidly induced gene expression of Smad7, which antagonizes the actions of the transforming growth factor beta/Smad pathway. Smad7 mRNA induction occurred throughout the epidermis and dermal cells as determined by in situ hybridization. Ultraviolet irradiation also caused reduced DNA binding of Smad3/4 in human skin in vivo. Reduced Smad3/4 DNA binding was observed within 4 h following irradiation. Taken together, these results demonstrate that ultraviolet and solar-simulated ultraviolet irradiation alter the transforming growth factor beta/Smad pathway in human skin in vivo. Ultraviolet induction of Smad7 and reduction of transforming growth factor beta2 and transforming growth factor beta type II receptor should diminish transforming growth factor beta signaling, and probably contribute to the decrease of transforming growth factor beta regulated type I and type III procollagen gene expression observed in ultraviolet and solar-simulated ultraviolet irradiated human skin in vivo.


Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates.
We have developed new solid phase methods for the synthesis of branched RNAs that mimic intronic lariat RNA intermediates. These methods produce branched oligoribonucleotide sequences of arbitrary length, base composition, and regiochemistry at the branchpoint junction. The methods utilize branching monomers that allow for the growth of each branch regioselectively from any of the hydroxyl positions (5′, 3′, or 2′) at the branch-point junction. The integrity and branchpoint connectivity of the synthetic products have been confirmed by HPLC and MS analysis, and cleavage of the 2′,5′ linkage by recombinant debranching enzyme. Nonhydrolyzable branched RNA analogues containing arabinose instead of ribose at the branchpoint junction were shown to inhibit debranching activity and, hence, represent “decoys” for sequestering RNA binding proteins thought to drive amyotrophic lateral sclerosis (ALS).


The surgical significance of Persian Gulf sand.
Foreign bodies, in particular sand and soil particles, can cause considerable reaction in wounds and remain in tissues indefinitely. The introduction of foreign material as a contaminant in wounds and intracavitary injuries to military personnel deployed in the Persian Gulf region can be a complicating factor in treatment. Samples of desert sand from the military operational areas of the Persian Gulf were analyzed and the acute local and systemic responses of intraperitoneal contamination determined in an experimental rat model.


Mandibular fracture: analysis of 293 patients treated in the Hospital of Clinics, Federal University of Uberlândia.
Mandibular fracture is the second most common facial fracture and there has been a significant increase in number of cases in the last years. Misidentification and inadequate treatment can take to permanent aesthetic or functional deformity. Evaluate cases of mandibular fracture reduction in the Hospital of Clinics of the Federal University of Uberlândia, from January of 1974 to December of 2002. Historical cohort. Two hundred and ninety-three cases of reduction of mandibular fractures were retrospectively analyzed according to factors related to: patient, trauma, signs and symptoms, and surgical treatment. There has been a clear tendency of increase of the number of mandibular fractures along the years. There was higher prevalence in male (4:1), with occurrence peak between 20 to 29 years old. The principal causes of fracture in this study were traffic accidents and violence, representing 72.4%. One hundred and thirty-five patients presented only one fracture. The most injured sites were, in decreasing order, symphysis, condyle, angle, body, ramus, and coronoid. We performed closed reduction (28), open reduction (213) and association of the two (11 patients); 56.8% of the patients were treated within the first 3 days; and, 50.4% were discharged from the hospital until the first postoperative day. About 10% of the patients presented complications, being osteomyelitis the most frequent one. The incidence of mandibular fractures was remarkably larger in the male sex, during the third decade of life. The most common cause was traffic accident, and symphysis and condyle were the most injured sites. Isolated fractures occurred in over half of the cases. Most of the patients were treated in the first three days and were discharged until the first postoperative visit. Closed reduction was the treatment most commonly employed. The most frequent complication was osteomyelitis.


Esophagectomy for cancer: clinical concerns support centralizing operations within the larger hospitals.
Esophagectomy needs experienced surgical techniques and a well-trained perioperative care team. There are now many reports that the mortality rate after esophagectomy is higher in those hospitals with a low volume of esophagectomy and/or low surgeon's volume. The purpose of this study is to decide the respective numbers of esophagectomy operations per year to define low-volume and high-volume hospitals in Japan. If medical policy aims to further reduce mortality and morbidity associated with esophagectomy, then esophagectomy operations should be further centralized, away from low-volume hospitals, into high-volume hospitals. The Japanese Association for Thoracic Surgery has accumulated the surgical outcomes from 31 380 esophagectomy operations, registered from 709 institutes during the period from 2001 to 2006. These institutes are here classified into six groups according to the number of esophagectomy operations per year as 4 or less, 5-9, 10-19, 20-39, 40-79, and 80 or more. Using a statistical model-selection procedure by information criteria, these six groups are then classified into three categories as low-volume, medium-volume, and as high-volume hospitals. Among the 31 380 patients registered, overall, 390 patients (1.2%) died within 30 days, and 1187 patients (3.8%) died during the primary hospital stay. The odds ratio of the greatest volume group to the minimum volume group was 0.307 for the 30-day mortality rate, and 0.288 for the in-hospital mortality rate. For both the 30-day mortality rate and the in-hospital mortality rate, a hospital with less than five esophagectomy operations per year was classified as a low-volume hospital. A hospital with 40 or more esophagectomy operations per year was classified as a high-volume hospital. Concerning the number of esophagectomy operations performed per year in Japan, low-volume hospitals are defined as those where esophagectomy is performed less than five times per year, and high-volume hospitals are defined as those where esophagectomy is performed 40 or more times per year. If medical policy in Japan aims to further decrease the mortality after esophagectomy, then esophagectomy operations should be limited in these identified low-volume hospitals.


A dear teacher.
We learn much of our professional expectations from colleagues, especially those we admire. This report describes one dentist's disappointment in extending the same professional relationship to an associate that he had experienced when he first associated. In the absence of a written employment agreement, the new associate set up practice a few minutes away, stealing staff and patients. The silver lining has been greater office efficiency and a richer relationship with patients and staff.


Peierls to superfluid crossover in the one-dimensional, quarter-filled Holstein model.
We use continuous-time quantum Monte Carlo simulations to study retardation effects in the metallic, quarter-filled Holstein model in one dimension. Based on results which include the one- and two-particle spectral functions as well as the optical conductivity, we conclude that with increasing phonon frequency the ground state evolves from one with dominant diagonal order-2k(F) charge correlations-to one with dominant off-diagonal fluctuations, namely s-wave pairing correlations. In the parameter range of this crossover, our numerical results support the existence of a spin gap for all phonon frequencies. The crossover can hence be interpreted in terms of preformed pairs corresponding to bipolarons, which are essentially localized in the Peierls phase, and 'condense' with increasing phonon frequency to generate dominant pairing correlations.


Clinical Predictors of Response to Prednisone Plus Cyclophosphamide in Patients with Idiopathic Membranous Nephropathy.
Complete remission (CR) and partial remission (PR) are beneficial to the long-term outcome of patients with idiopathic membranous nephropathy (iMN). However, we are lacking in studies that evaluate the clinical predictors of response to treatment with prednisone plus cyclophosphamide (CP). The objectives of the study are to identify clinical factors that could predict clinical remission or relapse in patients with iMN who were treated with prednisone plus i.v. CP therapy. This retrospective study recruited a total of 102 eligible patients diagnosed with biopsy-proven iMN between January 2010 and December 2013 in our center. All subjects were treated with prednisone plus i.v. CP for at least 6 months. Primary outcome was remission, including both CR and PR. Demographic data and clinical data at baseline and month 3 of treatment with CP were assessed. The proportion of patients with remission (both CR and PR) was 82.4%, over an average follow-up duration of 15 (10-27.5) months. Fifty-two of them experienced a CR. Baseline proteinuria and the reduction of proteinuria at month 3 of CP treatment were independent predictors of remission (p < 0.05) and CR (p < 0.05). In addition, the presence of a PR versus a CR was associated with the risk of relapse (hazards ratio 21.521, 95% CI 4.534-102.150, p < 0.001). Patients with low proteinuria at baseline and high reduction of proteinuria at month 3 of treatment with CP were more likely to achieve remission and CR. The presence of only a PR may act as a useful predictor of relapse after completion of CP therapy.


Smoking cessation care provision in Australian alcohol and other drug treatment services: A cross-sectional survey of staff self-reported practices.
Clinical practice guidelines recommend alcohol and other drug (AOD) services assess client's smoking status and offer smoking cessation care (SCC) to all smokers. The aim of this study was to examine Australian AOD program staff report of recommended SCC practices: assessment and recording of smoking status; and the provision of 9 types of SCC. The study also assessed how the decision to provide SCC is made and the AOD program service and AOD staff characteristics associated with the provision of SCC. Between July-October 2014, treatment staff from 31 Australian AOD services participated in an online cross-sectional survey. In addition, a site contact at each service was interviewed to gather service related data. Overall, 362 AOD program staff participated (response rate=57%) and 62% estimated that client smoking status was recorded for the "majority or all" of their clients. About a third (33%) reported that they "always" provide verbal advice to their clients to quit smoking, 18% "always" offered free or subsidized NRT and 16% "always" followed-up to check on client quit progress. Thirty percent reported that the decision to provide SCC was made on a client by client basis and 26% offered SCC only when the client requested assistance. Government-managed services, age and gender of AOD program staff were significantly associated with the provision of SCC. Most AOD program staff report that smoking status is recorded for the majority of their clients however, the frequency with which SCC practices are delivered is low and the decision to provide care is arbitrary.


[Study of the transversal repartition of the electrical field of paroxysmal discharges in petite mal epilepsies (author's transl)].
A precise analysis of the topography of the EEG critical discharges of Petit Mal, permits a description of two principal varieties, depending whether their electrical field presents two lateral and symmetrical peaks--usually on frontal areas--('lateral variety') or one peak on the mediosagittal line ('medial variety') of the scalp. The relationship which exists between the lateral distribution of EEG discharges and the 'simple' aspect of the absences, on the one hand, and the medial distribution with the 'complex' aspect, on the other, is so close that one is led to hypothesize two distinct epileptogenic processes.


Clinical and molecular analysis of a Japanese boy with Morquio B disease.
Morquio B disease was found in a 15-year-old Japanese boy who presented with progressive generalized skeletal dysplasia without neurological manifestations. Mild keratan sulfaturia was found, and beta-galactosidase was deficient in fibroblasts. Gene analysis revealed two mutant alleles, 83Tyr-->His (Y83H) and 482Arg-->Cys (R482C). The former expressed a low enzyme activity (2-5% of normal), and the latter expressed no detectable enzyme activity.


Comparison of the specificty of human and bovine tuberculin PPD for testing cattle. 1--Republic of Ireland.
A tuberculin testing trial in cattle was carried out in the Republic of Ireland to compare the specificity for bovine tuberculosis of a human purified protein derivative (PPD) tuberculin (Weybridge) with that of a bovine PPD (Rotterdam), and to determine whether discrimination between specific and non-specific reactions to mammalian tuberculin is better with doses of tuberculins smaller than those traditonally used for testing cattle. Tests were carried out in 510 cattle, 395 of which were shown by post mortem examination to be tuberculous and 115 non-tuberculous. Three dilutions at five-fold intervals of both mammalian tuberculins were used together with two dose levels of avian tuberculin PPD (Weybridge), and all reactions were measured both by increase in skin fold thickness and by diameter of induration. In the environment of this trial, the bovine PPD was shown to be more specific for bovine tuberculosis than the human PPD, and particularly in differentiating from "skin tuberculosis". There was no indication of greater specificity at lower doses of tuberculin. Measurement of induration diameter proved a satisfactory alternative method of reading tuberculin reactions in cattle under field conditions.


Listings.
Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Jo Barr, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867).


The elusive character of agrammatism.
Traditionally, agrammatism was viewed as a restricted disorder of speech production which was associated with Broca's aphasia. This view has been replaced by a more complex picture which involves a range of linguistic impairments in both language production and comprehension. These disorders have been variously characterized as deficits, in the representation of linguistic structures and deficits in the on-line computation of sentence structures and their interpretations. A variety of analyses of production and comprehension in agrammatism, invoking both representational and computational analyses, are reviewed. Each has inadequacies, but, at the same time, it is argued that each also advances the understanding of agrammatism.


A new protocol for ovarian carcinoma.
We are presenting the actual protocol for ovarian epithelial carcinoma and we want to emphasize that a surgical procedure must be necessary, in almost all cases, with a double objective: one, staging accuracy of tumor spread and two, surgical treatment in its different modalities. Chemotherapy as adjuvant therapy becomes a primary treatment even in early stages. New drugs such as CDDP, Hexametilmelanine and epirubicin, associated in different proportions have improved the overall survival in ovarian cancer. Nevertheless there is a very good series in the response, when external radiotherapy to the total pelvis or to the total abdomen, is indicated. The best benefit in overall survival was obtained in stages III and IV when a combination of surgery, polychemotherapy including CDDP and irradiation was indicated. There is united agreement that the factor that influences decisively in survival is the size of the residual mass, and that independently of the indicated treatment. We must adjust the best type of surgery in order to remove the tumor mass localized in different areas. We think that this point is mandatory in order to get a good response with the adjuvant therapy association.


[Preparation of bovine lipid-free hemoglobin].
A new method for preparation of Hb solution free of stromal lipid was described. Almost all the lipid in fresh hemolysate of bovine red blood was removed with hydrophobic interaction chromatography (HIC) in the presence of 2% PEG4000, 5% PEG4000, 2%PEG10000 or 5%PEG10000. With the adding of 5%PEG4000, the 80% of recovery of Hb in HIC was obtained and the maximum lipid absorbed by hydrophobic medium, butyl agarose -6B was 86.6 mg/mL. The activity (P50) of hemoglobin preparation was 3386.4 Pa torrs, and the Hill number was 2.54, which were near to that of the native red blood cells. The mechanism of removing lipid by HIC and the function of PEG in the process were discussed.


Structural elucidation of a new flavone from Sarcopyramis nepalensis.
A novel flavone, named 4'-methoxy-3',5,7-trihydroxy-8-(1''-(3''',4''',5'''-trihydroxyphenyl)ethyl)flavone (1), was isolated from Sarcopyramis nepalensis, along with two known compounds syringaresinol (2) and aralidioside (3). Their structures were established by the spectroscopic analysis, especially by 2D NMR. All of the three compounds were isolated from the plant for the first time.


Orally inhaled migraine therapy: Where are we now?
Migraine is a debilitating disease that affects 9% of men and 19% of women worldwide with high socio-economic and personal impact. Surveys indicate that migraineurs are among the most dissatisfied with available therapeutic options, predominantly given via oral or injectable routes, citing side effects as the primary complaint. Orally inhaled therapies have the potential to offer faster onset of action with fewer side effects compared to existing therapies, yet development has stalled. Despite emerging therapies such as calcitonin gene-related peptide antagonists, there are still good opportunities for repositioning migraine drugs via the inhaled route.


Chemical Exchange Saturation Transfer MR Imaging: Potential Clinical Applications.
Chemical exchange saturation transfer (CEST) measurements hold great promise as the next step in magnetization transfer imaging and possibly allow for in vivo quantification of many clinically relevant parameters, including pH, temperature, and amide concentration. Therefore, it is a valuable method to add to the MR imaging toolbox. The aim of this article was to review the methods for the acquisition of CEST data and necessary postprocessing. CEST research is very much a field still in development, and initial explorations in clinical applications are shown to illustrate the potential of CEST as a new contrast mechanism.


Electrophoretic analysis of HeLa cell and human liver nucleolar proteins and antigens.
The major antigens in HeLa nucleolar extracts recognized by immunoblots with rabbit antisera had molecular weights of 145, 110, and 34 kd. The major antigens in the HeLa nucleolar residues had molecular weights of 145, 110, 86, 68, 55, 48, and 34 kd. In the liver, the major antigens in the nucleolar extracts had molecular weights of 86 and 76 kd. In the liver residues, the major antigens had molecular weights of 110, 86, 76, 65, and 55 kd. On two-dimensional gels stained with Coomassie blue, the HeLa nucleolar extract contained large amounts of protein B23 and lesser amounts of protein C23. In the liver nucleolar samples separated on two-dimensional (2-D) gels, protein 55/7.6 (Mr/pI) was the major protein in the extract. Lesser amounts of protein B23 were identified. Addition of protease inhibitors markedly improved the quality of the protein samples as shown in one-dimensional gel patterns for liver nucleolar proteins and to a lesser extent for HeLa nucleolar proteins. In the 2-D immunoblots of the HeLa extract and HeLa residues, the major stained band was protein C23 (110/5.2-5.6). In the liver extract, the major bands were 70/5.8-7 and 60/5.8-7. With a monoclonal antibody (MS-3) to protein C23 a 76/5.8 band was more notable in the residue which supported the results of the Coomassie blue and immunostains with rabbit antinucleolar antibodies. Some degradation products of protein C23 were observed in both the liver extract and the liver residue despite the use of protease inhibitors. Protein C23 along with other proteins are major antigens in HeLa nucleoli. In human liver nucleoli, a major protein 55/7.6 was identified which was not observed in the HeLa extracts. These studies show that a combination of protease inhibitors markedly reduced degradation of proteins in liver samples and provided a more satisfactory sample for comparison with HeLa cells. Qualitative and quantitative differences were found in the nucleolar proteins by Coomassie blue and immunostaining.


Photochemical Formation of Cyclobutane Pyrimidine Dimers in DNA through Electron Transfer from a Flanking Base.
Electron transfer (ET) to a pyrimidine base from external moieties is a common step involved in the quenching or repair of the cyclobutane pyrimidine dimer (CPD). In contrast, we present a pathway that is initiated by an ET from a flanking guanine base to a pyrimidine base, leading to the formation of a CPD. We studied a T5mCG sequence with a methylated cytosine and our results demonstrate that the pathway involves the formation of an exciplex and intersystem crossings. This pathway also provides an explanation for why the mutational hot spots are correlated with the methylated CpG sequences, which has been a significant issue in cancer research.


Grateful students are motivated, engaged, and successful in school: Cross-sectional, longitudinal, and experimental evidence.
Previous research on gratitude has mostly focused on its effects on well-being. However, scant attention has been paid to how gratitude is associated with key learning-related outcomes. The aim of this series of studies was to examine how gratitude is associated with students' motivation, engagement, and achievement. Study 1, a cross-sectional study, found that gratitude was positively associated with higher levels of autonomous motivation and engagement (rs ranging from 0.17 to 0.20, p < .05). Study 2, a longitudinal study, found that gratitude was concurrently and prospectively associated with autonomous motivation (rs ranging from 0.20 to 0.78, p < .05), self-reported and teacher-reported engagement (rs ranging from 0.11 to 0.68, p < .05), and achievement (rs ranging from 0.38 to 0.41, p < .05). Study 3, an experimental study, showed that students who were in the gratitude condition perceived themselves to be more engaged (Cohen's d ranging from 0.58 to 0.63) compared to those in the control condition. The three studies provided converging evidence that grateful students have better learning-related outcomes. Theoretical and practical implications are discussed.


Comparison of PAX-2, RCC antigen, and antiphosphorylated H2AX antibody (gamma-H2AX) in diagnosing metastatic renal cell carcinoma by fine-needle aspiration.
Diagnosing metastatic renal cell carcinoma (RCC) by fine-needle aspiration (FNA) can be challenging. Existing antibodies supporting a diagnosis of RCC, including CD10 and RCC-Ma, have problems with specificity and interpretation. In this report, we evaluate the use of two newer immunostains, PAX-2 and gamma-H2AX, which to our knowledge have not been studied in FNA material, in the diagnosis of metastatic RCC and in comparison with RCC-Ma. 29 cases of metastatic RCC were identified as well as a TMA of an additional 30 RCC cases. In the case cohort, RCC-Ma in a membranous pattern of staining identified 15/27 (56%) metastatic RCC, although interpretation was made difficult in many cases due to focality of staining and non-specific cytoplasmic staining. PAX-2 stained 23/29 (79%) of tumors in a nuclear stain, most strongly. Gamma-H2AX stained 19/26 (73%) of metastatic RCC strongly in a nuclear stain. In the TMA, strong, diffuse nuclear staining with gamma-H2AX was present in 22/30 RCC (73%). If weak staining was also included as positive, 26/30 (87%) were positive. PAX-2 stained RCC TMA with a lower percentage at 56%, including weaker staining intensity. Both PAX-2 and gamma-H2AX demonstrated patchy staining of normal renal tubules, PAX-2 to a greater extent. Both PAX-2 and gamma-H2AX are sensitive markers for the diagnosis of metastatic RCC, with improved ease of interpretation when compared with RCC-Ma. A combination of all 3 markers identified 87% of cases, and failure to stain for both PAX-2 and gamma-H2AX suggests against, but does not disprove, a diagnosis of RCC.


Diffusion tensor imaging measures of normal appearing white matter in patients who are aging, or have amnestic mild cognitive impairment, or Alzheimer's disease.
To evaluate whether cerebral white matter integrity is related to cognitive function, and whether diffusion tensor imaging (DTI) could differentiate amnestic mild cognitive impairment (aMCI) from Alzheimer's disease (AD), 12 patients with AD, 12 with aMCI, and 12 controls were recruited for this study. Cognitive functions of all subjects were assessed using the Mini-Mental State Examination (MMSE) and AD Assessment Scale - Cognitive Subscale (ADAS-Cog). DTI studies were acquired, and fractional anisotropy (FA) and mean diffusivity (MD) values of normal-appearing white matter (NAWM) in multiple brain regions were obtained. Results showed that MMSE and ADAS-Cog subscores were significantly associated with white matter integrity of the temporal-parietal lobes. A decrease in FA values and an increase in MD values in multiple cortical regions were confirmed in patients with AD compared to controls. MD values in the posterior region of the corpus callosum in aMCI differed from those of early AD. Significant reductions of FA values in the NAWM of the parietal lobe was observed in aMCI compared to controls. Our data indicate that the microstructural white matter integrity in the temporal-parietal lobes is gradually impaired in the progressive process of AD, and that splenium MD values could be used as a biomarker differentiating aMCI from AD.


Application of the phosphoramidate ProTide approach to 4'-azidouridine confers sub-micromolar potency versus hepatitis C virus on an inactive nucleoside.
We report the application of our phosphoramidate ProTide technology to the ribonucleoside analogue 4'-azidouridine to generate novel antiviral agents for the inhibition of hepatitis C virus (HCV). 4'-Azidouridine did not inhibit HCV, although 4'-azidocytidine was a potent inhibitor of HCV replication under similar assay conditions. However 4'-azidouridine triphosphate was a potent inhibitor of RNA synthesis by HCV polymerase, raising the question as to whether our phosphoramidate ProTide approach could effectively deliver 4'-azidouridine monophosphate to HCV replicon cells and unleash the antiviral potential of the triphosphate. Twenty-two phosphoramidates were prepared, including variations in the aryl, ester, and amino acid regions. A number of compounds showed sub-micromolar inhibition of HCV in cell culture without detectable cytotoxicity. These results confirm that phosphoramidate ProTides can deliver monophosphates of ribonucleoside analogues and suggest a potential path to the generation of novel antiviral agents against HCV infection. The generic message is that ProTide synthesis from inactive parent nucleosides may be a warranted drug discovery strategy.


A density-functional study for the liquid-vapor coexistence curve of nitrogen fluid.
We have used a density-functional theory based on the interaction site model to predict the liquid-vapor coexistence curve of nitrogen fluid. The pressure and chemical potential were calculated from thermodynamic integrations. The different paths of thermodynamic integration provide slightly different predictions for the liquid-vapor coexistence curve. However, these critical points and coexistence curves evaluated by the theory are in qualitative agreement with the experimental data. The theoretical coexistence curves scaled to critical constants agree with the experimental data quantitatively.


Haemoglobin C protects against clinical Plasmodium falciparum malaria.
Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.


Two replication initiators - one mechanism for replication origin opening?
DNA replication initiation has been well-characterized; however, studies in the past few years have shown that there are still important discoveries to be made. Recent publications concerning the bacterial DnaA protein have revealed how this replication initiator, via interaction with specific sequences within the origin region, causes local destabilization of double stranded DNA. Observations made in the context of this bacterial initiator have also been converging with those recently made for plasmid Rep proteins. In this mini review we discuss the relevance of new findings for the RK2 plasmid replication initiator, TrfA, with regard to new data on the structure of complexes formed by the chromosomal replication initiator DnaA. We discuss structure-function relationships of replication initiation proteins.


Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity.
The recombinant growth factors (GFs) erythropoietin (Epo) and granulocyte-macrophage colony stimulating factor (GM-CSF) have important roles in the management of cancer patients. However, the effects of these GFs at a cellular level are not well understood. We examined the effect of GFs alone, and in combination with cytotoxic chemotherapy, in a panel of seven cell lines. Flow cytometric analysis showed varying levels of receptor expression, which correlated with phosphorylated MAPK expression. Additionally, there were also concomitant increases in BCL-2 protein levels in those cells with high levels of MAPK activation. Although culturing cells with Epo or GM-CSF did not alter cell viability by themselves, GF pretreatment in cell lines expressing higher receptor levels resulted in a reduced magnitude of cell kill following exposure to cytotoxic IC50 concentrations of cisplatin. Subsequent co-culture with either the MEK inhibitor U0126 or the GM-CSF antagonist E21R negated this induced resistance to cytotoxic chemotherapy, confirming the importance of the GF receptor as well as MAPK in mediating these effects. These results suggest that the use of GFs during chemotherapy may be detrimental in those cancers expressing higher levels of the specific receptor. Conversely, our results also suggest that GFs are safe to use in chemotherapeutic regimens if the cancer cells do not overexpress the particular receptor.


Pressure-induced changes in the molecular organization of a lipid-peptide complex: polymyxin binding to phosphatidic acid membranes.
The effect of 100 atm pressure on the organization of the lipid-peptide complex formed between polymyxin and dipalmitoyl phosphatidic acid has been investigated. Phase transition curves were obtained by electron paramagnetic resonance by measuring the partition coefficient of the spin label, 2, 2, 5, 5-tetramethylpiperidine-N-oxyl. The three-step phase transition curve previously obtained with fluorescence polarization measurements was confirmed, demonstrating three distinct phosphatidic acid domains in the bilayer. Pressure increases binding of polymyxin to phosphatidic acid bilayers and alters the proportions of the two domains that differ in the mode of binding between phosphatidic acid and polymyxin. The binding curves of polymyxin to phosphatidic acid bilayers wre determined and it was shown that application of pressure reduces the cooperativity of the binding curve.


The physiological role of glucokinase binding and translocation in hepatocytes.
The compartmentation of glucokinase in the hepatocyte is regulated by the extracellular glucose concentration and by substrates that alter the concentration of fructose 1-phosphate in the hepatocyte. At low glucose concentrations, that mimic the fasted state, glucokinase is sequestered in an inactive state bound to the 68 kDa regulatory protein in the nucleus. In these conditions the rate of glucose phosphorylation is less than 15% of the total glucokinase activity. An increase in extracellular glucose concentration, within the range occurring in the portal vein in the absorptive state, or low concentrations of fructose or sorbitol (precursors of fructose 1-phosphate), cause the translocation of glucokinase from the nucleus to the cytoplasm and this is associated with a corresponding increase in glucose phosphorylation. The effect of glucose on translocation is mimicked by mannose which is also phosphorylated by glucokinase as well as by competitive inhibitors of glucokinase (mannoheptulose and 5-thioglucose) which are not phosphorylated. Various lines of evidence suggest that the action of these analogues is most likely due to binding to an allosteric or non-catalytic site. The saturation curve of glucose phosphorylation in intact hepatocytes is sigmoidal with an S0.5 of approximately 20 mM and a Hill coefficient approximately 2. This saturation curve can be explained by the activity of glucokinase in the cytoplasmic compartment. Translocation of glucokinase from the nucleus to the cytoplasm in response to precursors of fructose 1-phosphate (which cause dissociation of glucokinase from the regulatory protein) is associated with stimulation of glucose phosphorylation, glycolysis and glycogen synthesis. Using Metabolic Control Analysis to determine the Control Coefficient (Control Strength) of cytoplasmic (free) glucokinase on glucose metabolism it can be shown that the free glucokinase activity has a very high control strength on glycogen synthesis (CFGKJ > 1), indicating a major role of translocation of glucokinase in the control of hepatic glycogen synthesis. Overexpression of glucokinase in hepatocytes by adenovirus-mediated glucokinase overexpression is associated with a marked increase in glycogen synthesis. The relation between glycogen synthesis and enzyme overexpression is sigmoidal with an enzyme concentration causing half-saturation (S0.5) in the physiological range. The high Control Coefficient of glucokinase on hepatic glycogen synthesis explains the abnormalities of hepatic glycogen synthesis in patients with a single mutant allele of the glucokinase gene (Maturity Onset Diabetes of the Young, type 2).


Nascent RNA and the Coordination of Splicing with Transcription.
SUMMARYAt each active protein-encoding gene, nascent RNA is tethered to the DNA axis by elongating RNA polymerase II (Pol II) and is continuously altered by splicing and other processing events during its synthesis. This review discusses the development of three major methods that enable us to track the conversion of precursor messenger RNA (pre-mRNA) to messenger RNA (mRNA) products in vivo: live-cell imaging, metabolic labeling of RNA, and RNA-seq of purified nascent RNA. These approaches are complementary, addressing distinct issues of transcription rates and intron lifetimes alongside spatial information regarding the gene position of Pol II at which spliceosomes act. The findings will be placed in the context of active transcription units, each of which-because of the presence of nascent RNA, Pol II, and features of the chromatin environment-will recruit a potentially gene-specific constellation of RNA binding proteins and processing machineries.


Influence of GABA in the nucleus of the solitary tract on blood pressure in baroreceptor-denervated rats.
We have previously reported that inhibition of the nucleus of the solitary tract (NTS) in chronically sinoaortic baroreceptor-denervated (SAD) rats has no effect on blood pressure in contrast to the marked increase in blood pressure it elicits in baroreceptor-intact rats. This could result either from a lack of tonic excitatory input to this region or from overriding inhibition of NTS neurons involved in the control of blood pressure. The present study aimed to distinguish between these two possibilities by examining the changes in blood pressure elicited by injection of bicuculline (Bic), a gamma-aminobutyric acid (GABA) antagonist, into the NTS of SAD and control rats. In chloralose-anesthetized baroreceptor-intact rats or acutely SAD rats, injection of 10 pmol Bic into the NTS elicited minimal changes in blood pressure. In contrast, in chronic SAD rats injection of Bic into the NTS elicited a large decrease in blood pressure. The maximal decrease in blood pressure elicited by Bic in chronic SAD rats was equivalent to the maximal decrease in blood pressure that could be evoked by direct excitation of the NTS with L-glutamate. These results suggest that the lack of a tonic role of the NTS in the regulation of blood pressure in chronic SAD rats is a result of maximal GABA-mediated inhibition of relevant NTS neurons.


Impact of intrasac thrombus and a patent inferior mesenteric artery on EVAR outcome.
To assess the significance of a patent inferior mesenteric artery (IMA) and presence of intrasac thrombus on the outcome of endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). Between June 2004 and June 2007, 114 AAA patients (100 men; mean age 75 years, range 56-87) treated electively with a bifurcated stent-graft were assessed with computed tomography pre- and postoperatively. Incidences of type II endoleaks and reinterventions were compared with preoperative intrasac thrombus and IMA patency. Over a mean follow-up of 19 months (range 6-38), there was no aneurysm rupture. Eleven (11%) of 101 patients with and 7 (54%) of 13 patients without preoperative intrasac thrombus presented with a type II endoleak (p<0.01). The postoperative change in aneurysm diameter was 0 mm (-20 to 16) in 18 patients with type II endoleak and -9 mm (-30 to 18) in sealed aneurysms (p<0.001). Fourteen (78%) type II endoleaks originated from lumbar arteries and 4 (22%) from the IMA in spite of the fact that most patients (69%) had a patent IMA. There were 5 reinterventions for type II endoleak with expansion of the sac. The reinterventions did not seem related to intrasac thrombus or a patent IMA. Prophylactic embolization of the IMA was unsuccessful in 4 (33%) cases. In this series, type II endoleaks inhibited sac shrinkage and occurred more frequently in aneurysms without intrasac thrombus. Most type II endoleaks originated from lumbar arteries and not from the IMA. Prophylactic embolization of the IMA does not seem justified and is not always technically successful.


Acrylic coatings with surprising antifogging and frost-resisting properties.
We report an unusually effective antifogging/frost-resisting coating based on conventional acrylic polymers. The intriguing antifogging property originated from the delicate balance between the hydrophilicity and hydrophobicity of the acrylic copolymers of 2-(dimethylamino)ethyl methacrylate and methyl methacrylate, as well as between the water-swellability of the copolymer and the cross-linked network due to ethylene glycol dimethacrylate.


Dopaminergic Therapy for Restless Legs Syndrome/Willis-Ekbom Disease.
Dopaminergic therapies have been a mainstay of restless legs treatment and are endorsed as first-line therapies by multiple professional societies. This article summarizes the differences and similarities among the dopamine agonists with attention to pharmacology, efficacy, side effects, and dosing.


[Identification of Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis by polymerase chain reaction].
Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the main human pathogens that cause meningitis. Primers omp2, lytA and crgA were evaluated with H. influenzae, S. pnumoniae and N. meningitidis DNA in a multiplex PCR, determining the sensitivity and the specificity of the technique. Primers for H. influenzae outer membrane protein (omp2, 1000 pb), S. pneumoniae autolysin (lytA, 395 pb) and N. meningitidis, contact regulated gene (crgA, 230 pb) were evaluated in a multiplex PCR, determining the sensitivity and the specificity of the technique. Reproducible results were obtained with 50 nM of each of the three primers and annealing temperature of 57 degrees C in the multiplex PCR, obtaining a sensitivity of 12.5 fg for H. influenzae and S. pneumoniae and 3.12 fg for N. meningitidis. No cross reactions with other microorganisms agents of meningitis or related with the genera, appeared. The results for sensitivity and specificity suggest that the evaluated primers can be used for the development of a PCR in a multiplex format to the identification of the three main pathogens that cause meningitis.


Further study on fallout 3H ingestion in Akita, Japan.
To study fallout 3H ingestion in Japan, 16 separate food-group samples were collected from Akita City in northern Japan during early summer and late autumn in 1986. Furthermore, total diet samples which are duplicate composite food samples consumed by five or six persons for a period of 1 d were also obtained in Akita City. The 3H concentration in free water and that in a tissue-bound form were determined separately. Seasonal changes of 3H concentration in the food samples and the total diet samples were not found clearly. The average 3H concentration in the free water including tap water was 1.6 Bq L-1. The mean ratio of specific activity of tissue-bound 3H to that of 3H in free water was found to be 1.2. The average total 3H ingestion was estimated to be 4.0 Bq d-1, while the proportion of tissue-bound form 3H ingestion to total 3H ingestion was 11%. Cereal was the greatest contributing food group to ingestion of tissue-bound 3H. These findings were consistent with our previous results for food samples collected in 1985.


[Acute respiratory distress revealing severe pulmonary leptospirosis].
We return a clinical case of leptospirose revelated by a complicated febrile harp pneumopathie of a sharp respiratory distress syndrome having required a transfer in resuscitation. The goal of our article is to recall that it is necessary to think systematically about a pulmonary shape of leptospirose facing an atypical pneumopahie.


Capillary electrophoresis-based separation techniques for the analysis of proteins.
CE offers the advantages of high speed, great efficiency, as well as the requirement of minimum amounts of sample and buffer for the analysis of proteins. In this review, we summarize the CE-based techniques coupled with absorption, LIF, and MS detection systems for the analysis of proteins mostly within the past 5 years. The basic principle of each technique and its advantages and disadvantages for protein analysis are discussed in brief. Advanced CE techniques, including on-column concentration techniques and high-efficiency multidimensional separation techniques, for high-throughput protein profiling of complex biological samples and/or of single cells are emphasized. Although the developed techniques provide improved peak capacity, they have not become practical tools for proteomics, mainly because of poor reproducibility, low-sample lading capacity, and low throughput due to ineffective interfaces between two separation dimensions and that between separation and MS systems. In order to identify the complexities and dynamics of the proteomes expressed by cells, tissues, or organisms, techniques providing improved analytical sensitivity, throughput, and dynamic ranges are still demanded.


Role of Ca2+-activated Cl- current during proarrhythmic early afterdepolarizations in sheep and human ventricular myocytes.
The proarrhythmic early afterdepolarizations (EADs) during phase-2 of the cardiac action potential (phase-2 EADs) are associated with secondary Ca2+-release of the sarcoplasmic reticulum. This makes it probable that the Ca2+-activated Cl- current [ICl(Ca)] is present during phase-2 EADs. Activation of ICl(Ca) during phase-2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase-2 EADs. The present study was designed to test this hypothesis. The contribution of ICl(Ca) during phase-2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch-clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 microm noradrenaline. In sheep myocytes, the ICl(Ca) blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.5 mm) abolished phase-1 repolarization of the action potential in all myocytes tested. This indicates that ICl(Ca) is present in all sheep myocytes. However, DIDS had no effect on phase-2 EAD characteristics. In human myocytes, DIDS neither affected phase-1 repolarization nor phase-2 EAD characteristics. In sheep ventricular myocytes, but not in human ventricular myocytes, ICl(Ca) contributes to phase-1 repolarization of the action potential. In both sheep and human myocytes, ICl(Ca) plays a limited role during phase-2 EADs.


[Primary ovarian actinomycosis].
A rare observation--ovarian actinomycosis in a woman of 42 which had clinical manifestations of chronic adnexitis and was diagnosed pathomorphologically--in described. Destructive variant of mycotic process resulted in pelvioperitonitis with a subsequent surgical operation. This case may be referred to as a primary genital actinomycosis.


MLC parameters from static fields to VMAT plans: an evaluation in a RT-dedicated MC environment (PRIMO).
PRIMO is a graphical environment based on PENELOPE Monte Carlo (MC) simulation of radiotherapy beams able to compute dose distribution in patients, from plans with different techniques. The dosimetric characteristics of an HD-120 MLC (Varian), simulated using PRIMO, were here compared with measurements, and also with Acuros calculations (in the Eclipse treatment planning system, Varian). A 10 MV FFF beam from a Varian EDGE linac equipped with the HD-120 MLC was used for this work. Initially, the linac head was simulated inside PRIMO, and validated against measurements in a water phantom. Then, a series of different MLC patterns were established to assess the MLC dosimetric characteristics. Those tests included: i) static fields: output factors from MLC shaped fields (2 × 2 to 10 × 10 cm2), alternate open and closed leaf pattern, MLC transmitted dose; ii) dynamic fields: dosimetric leaf gap (DLG) evaluated with sweeping gaps, tongue and groove (TG) effect assessed with profiles across alternate open and closed leaves moving across the field. The doses in the different tests were simulated in PRIMO and then compared with EBT3 film measurements in solid water phantom, as well as with Acuros calculations. Finally, MC in PRIMO and Acuros were compared in some clinical cases, summarizing the clinical complexity in view of a possible use of PRIMO as an independent dose calculation check. Static output factor MLC tests showed an agreement between MC calculated and measured OF of 0.5%. The dynamic tests presented DLG values of 0.033 ± 0.003 cm and 0.032 ± 0.006 cm for MC and measurements, respectively. Regarding the TG tests, a general agreement between the dose distributions of 1-2% was achieved, except for the extreme patterns (very small gaps/field sizes and high TG effect) were the agreement was about 4-5%. The analysis of the clinical cases, the Gamma agreement between MC in PRIMO and Acuros dose calculation in Eclipse was of 99.5 ± 0.2% for 3%/2 mm criteria of dose difference/distance to agreement. MC simulations in the PRIMO environment were in agreement with measurements for the HD-120 MLC in a 10 MV FFF beam from a Varian EDGE linac. This result allowed to consistently compare clinical cases, showing the possible use of PRIMO as an independent dose calculation check tool.


[Role of duodenal diversion in the treatment of gastro-esophageal reflux].
Total duodenal diversion (TDD) is an original and efficient form of surgical treatment for gastroesophageal reflux. This technique was performed in 11 patients for severe esophagitis by first intention or after previous surgery. Results were excellent on reflux but 3 patients developed functional complications of the operation. This morbidity must lead to restrain the indications of the TDD.


Testicular microlithiasis: Systematic review and Clinical guidelines.
There are no clear recommendations on how patients with testicular microlithiasis should be followed up. The aim of our systematic review is to give clinical guidelines based on the evidence in the literature. A web search was conducted during February 2018 based on Pubmed data, Embase and Cochrane database. The eligibility of articles was defined using the PICOS method, in concordance with the PRISMA recommendations. Fifty three articles were selected for our final synthesis. Our review highlighted an association between testicular microlithiasis and the already known risk factors of testicular germ cell tumor. The presence of testicular microlithiasis in patients with such risk factors increases more the risk of cancer. In the absence of risk factors, the risk to develop testicular cancer is similar to the risk in general population. In patients at risk to develop testicular cancer, observation versus testicular biopsy is debatable. We recommend an individualized approach based on the age of the patient, the presence of concurrent features of testicular dysgenesis syndrome, the fertility of the couple, the desire of paternity and the ultrasound pattern (bilateral and clustered vs. unilateral and limited).


Platelet-derived growth factor (PDGF)-BB inhibits AMPA receptor-mediated synaptic transmission via PDGF receptor-beta in murine nucleus tractus solitarius.
Although platelet-derived growth factor (PDGF)-BB activates PDGF receptor-beta (PDGFR-beta) and, in turn, inhibits the glutamate N-methyl-D-aspartate (NMDA) receptor function, whether PDGF-BB modulates the CNS function mediated by another glutamate receptors, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, remains poorly understood. Here we now report the inhibitory effect of PDGF-BB on the AMPA receptor function in the nucleus tractus solitarius (NTS) by using slice patch-clamp techniques. Excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of the tractus solitarius in mouse NTS second-order neurons. EPSCs were nearly completely eliminated by CNQX but not by MK-801, implying mediation through non-NMDA receptors. PDGF-BB significantly decreased the amplitude of EPSCs without affecting the mean decay time constant. This inhibitory effect was transient and reversible after removing PDGF-BB. Furthermore, PDGF-BB significantly reduced the amplitude of AMPA-induced currents in NTS neurons, which showed that PDGF-BB could suppress the AMPA receptor-mediated excitatory input via the postsynaptic mechanism. The inhibitory effect of PDGF-BB on EPSCs was not observed in mutant mice with conditional deletion of the PDGFR-beta gene in neurons. Together, these studies suggest that the PDGF-B/PDGFR-beta axis inhibits the AMPA receptor-mediated synaptic transmission that comprises the major part of the primary afferent to the NTS second-order neuron. The detected inhibitory action may be involved in the CNS regulation of the respiratory response.


Splenic lymphoma with villous lymphocytes. Report of first 2 cases from the Middle East.
Two cases of splenic lymphoma with villous lymphocytes (SLVL) were diagnosed on the basis of marked splenomegaly, circulating villous lymphocytes, serum IgM monoclonal paraprotein and bone marrow infiltration. Immunological studies confirmed the B cell phenotype (CD19+, CD20+, CD22+ and CD5- and CD25-). Ultrastructural studies revealed characteristic uneven villi with polar predisposition. Interferon-alpha therapy in 1 patient did not result in any clinical or hematological improvement. This is the first report of SLVL from the Middle East.


Eight weeks gait retraining in minimalist footwear has no effect on running economy.
To evaluate the effects of an eight week combined minimalist footwear (MFW) and gait-retraining intervention on running economy (RE) and kinematics in conventional footwear runners. Twenty-three trained male runners (age: 43 ± 10 years, stature: 177.2 ± 9.2 cm, body mass: 72.8 ± 10.2 kg, V̇O2max: 56.5 ± 7.0 mL min(-1) kg(-1)) were recruited. Participants were assigned to either an intervention group (n = 13) who gradually increased exposure to MFW and also implemented gait-retraining over an eight week period. RE and kinematics were measured in both MFW and conventional running shoes (CRS) at pre-tests and eight weeks, in a random order. In contrast the control group (n = 10) had no MFW exposure or gait retraining and were only tested in CRS. The MFW and gait re-training intervention had no effect on RE (p < .001). However, RE was significantly better in MFW (mean difference 2.72%; p = .002) at both pre and post-tests compared to CRS. Step frequency increased as a result of the intervention (+5.7 steps per minute [spm]; p < .001), and was also significantly higher in MFW vs. CRS (+7.5 spm; p < .001). Whilst a better RE in MFW was observed when compared to CRS due to shoe mass, familiarization to MFW with gait-retraining was not found to influence RE.