Superantigen genes encoded by the egc cluster and SaPIbov are predominant among Staphylococcus aureus isolates from cows, goats, sheep, rabbits and poultry.
In recent years several new staphylococcal enterotoxins (SEs) have been described, which currently have largely unknown frequencies of occurrence and roles in human or animal disease. One hundred and ninety-one Staphylococcus aureus isolates from cows (99), goats (39), sheep (23), rabbits (15), chickens (15) and a cat (1) were screened for SE genes sea-see, seg-seo and seq and for the tst gene encoding staphylococcal toxic shock syndrome toxin-1 using multiplex PCRs and individual PCRs for the seb and sek genes. One hundred and ten isolates tested positive for at least one of these 16 superantigen (SAg)-encoding genes. There were statistically significant differences in the frequencies of some of these SAg genes between isolates from different animals. No strain possessed either the sea or see gene. The sec gene was present in 51 isolates, the sed gene in eight and the seb gene in one. The seh gene was found in four strains and the sek and seq genes together in one isolate. The most common combinations of genes were the egc cluster, bearing the seg, sei, sem, sen and seo genes, in 47 isolates, the sec, sel and tst gene combination typical of the SaPIbov pathogenicity island in 44 isolates, the egc cluster lacking the seg gene in 11 isolates, the sed and sej genes in nine isolates, and the sec and tst genes without the sel gene in seven isolates. The higher frequencies of the sec and tst genes together and the lower frequencies of the egc gene cluster among the SAg gene-positive sheep or goat isolates compared to bovine isolates were statistically significant. Of 36 bovine isolates that were mitogenic for human T lymphocytes, four were negative for the 16 SAg genes tested for, while a further 14 gave borderline results in the mitogenicity assay, 12 of which were SAg gene-negative. Twenty-nine strains lacking all the SAg genes did not induce T-cell proliferation. This survey indicates that novel SE genes seg, sei, sel, sem, sen and seo along with the sec and tst genes predominate in S. aureus from animal hosts. The mitogenicity assays indicate that further uncharacterized SAgs may be present in bovine isolates.


Receptor use by vesicular stomatitis virus pseudotypes with glycoproteins of defective variants of measles virus isolated from brains of patients with subacute sclerosing panencephalitis.
The vaccine or Vero cell-adapted strains of measles virus (MV) have been reported to use CD46 as a cell entry receptor, while lymphotropic MVs preferentially use the signalling lymphocyte activation molecule (SLAM or CD150). In contrast to the virus obtained from patients with acute measles, little is known about the receptor that is used by defective variants of MV isolated from patients with subacute sclerosing panencephalitis (SSPE). The receptor-binding properties of SSPE strains of MV were analysed using vesicular stomatitis virus pseudotypes expressing the envelope glycoproteins of SSPE strains of MV. Such pseudotype viruses could use SLAM but not CD46 for entry. The pseudotype viruses with SSPE envelope glycoproteins could enter Vero cells, which do not express SLAM. In addition, their entry was not blocked by the monoclonal antibody to CD46, pointing to another entry receptor for SSPE strains on Vero cells. Furthermore, the unknown receptor(s), distinct from SLAM and CD46, may be present on cell lines derived from lymphoid and neural cells. Biochemical characterization of the receptor present on Vero cells and SK-N-SH neuroblastoma cells was consistent with a glycoprotein. Identification of additional entry receptors for MV will provide new insights into the mechanism of spread of MV in the central nervous system and possible reasons for differences between MVs isolated from patients with acute measles and SSPE.


Acute stress does not affect the impairing effect of chronic stress on memory retrieval.
Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.


A theoretical increase in infants' hepatic vitamin a is realized using a supplemented lactating sow model.
Vitamin A deficiency (VAD) is a public health problem affecting millions in developing nations. Supplementation for lactating women, whose needs are high, involves large oral doses of the preformed vitamin. The safety and efficacy of these doses has been inadequately studied. Lactating women typically receive 210 micro mol of retinyl ester during early lactation, but 420 micro mol has also been administered. If larger doses of vitamin A are not significantly more effective in preventing VAD in mothers and infants, then smaller doses would be recommended. We therefore examined the vitamin A concentration of milk from lactating sows (n = 15) that were provided two different doses of vitamin A (i.e., 1050 or 2100 micro mol, n = 6/group) or corn oil (n = 3), corresponding to doses given women on the basis of body weight. Compared with controls, an overall significant treatment effect was found (P = 0.0019), but there was no difference in milk concentration between treatment groups. Theoretically, applying the mean milk vitamin A concentrations of the groups through 12 h and values to 48 h from 4 sows, we estimate that an infant of a supplemented mother could realize an increase of +0.08 or 0.16 micro mol/g liver from the low or high dose, respectively.


Optic Disc Blood Flow Measured by Scanning Laser-Doppler Flowmetry Using a New Analysis Program.
Purpose: Using a new analysis program for scanning laser-Doppler flowmetry (SLDF) by a Heidelberg retina flowmeter (HRF), we studied the relation between flow and visual field or disc morphology.Subjects and Methods: In 42 eyes of 21 patients with normal tension glaucoma (NTG) the mean-flow of the HRF blood flow parameters at the disc rim was measured and analyzed by a new analysis program for perfusion maps (the SLDF analysis tool), to minimize the influence of large vessels or/and artifacts caused by small eye movements. We investigated whether difference of the mean-flow between a pair of eyes had any relation to differences between a pair of eyes in visual field indices and those in disc morphological measurements of the Heidelberg retina tomograph.Results: We found statistically significant correlations between the mean-flow and optic disc parameters (Disk Area, Cup Area, Height Variation Contour, Cup Volume, Rim Volume, Mean RNFL Thickness). We found no statistically significant correlations between the mean-flow and visual field parameters (mean deviation, corrected pattern standard deviation).Conclusion: The results suggested that eyes with less flow in the optic disc rim have more advanced glaucomatous morphological changes.


Elective Neck Dissection for Head and Neck Cutaneous Squamous Cell Carcinoma with Skull Base Invasion.
Objectives Skull base invasion from cutaneous squamous cell carcinoma (cSCC) via perineural spread affects survival and the rate of regional metastasis. Our objective is to investigate the factors associated with elective neck dissection (END) in this population and the survival difference with END compared with observation for patients with a cN0 neck. Study Design Case series with chart review. Setting Academic. Subjects and Methods Patients were treated surgically for head and neck cSCC with skull base invasion via perineural spread with a cN0 neck from 2004 to 2014. Clinicopathologic data were collected and analyzed. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Results Fifty-nine patients met inclusion criteria: 28 underwent an END and 31 underwent neck observation. Free tissue transfer reconstruction was significantly associated with END ( P < .001). Patients treated with an END had significantly improved 5-year DFS (57% and 32%, P = .042) and OS (60% and 37%, P = .036) compared with those who were observed and a significantly reduced rate of regional recurrence (9% and 37%, P = .024). The rate of occult nodal metastasis identified with END was 36% and is approximately equal to the regional failure rate of the neck observation group (37%). Conclusion END was more commonly used in cases requiring free tissue transfer. The use of END for head and neck cSCCs that have invaded the skull base is not routinely performed but was found to be associated with a survival advantage and reduced regional recurrence rate.


Flavour, emulsifiers and colour are the most frequent markers to detect food ultra-processing in a UK food market analysis.
To elucidate which markers of ultra-processing (MUP) and their combinations are best suited to detect ultra-processed food (UPF). The study was based on the 206 food and 32 beverage items of the Oxford WebQ which encompass all major foods consumed in the UK. For each Oxford WebQ question, ingredient lists of up to ten matching different commercial products (n 2146) were researched online using data from the two market leaders of groceries in the UK sorted by relevance (Tesco) and by top sellers (Sainsbury's), respectively. According to the NOVA classification, sixty-five MUP were defined, and if the ingredient list of a food product was positive for at least one MUP, it was regarded as UPF. The percentage of UPF items containing specific MUP was calculated. In addition, all combinations of two to six different MUP were assessed concerning the percentage of identified UPF items. Cross-sectional analysis. None. A total of 990 products contained at least one MUP and were, therefore, regarded as UPF. The most frequent MUP were flavour (578 items, 58·4 % of all UPF), emulsifiers (353 items, 35·7 % of all UPF) and colour (262 items, 26·5 % of all UPF). Combined, these three MUP detected 79·2 % of all UPF products. Detection rate increased to 88·4 % of all UPF if ingredient lists were analysed concerning three additional MUP, that is, fibre, dextrose and firming agent. Almost 90 % of all UPF items can be detected by six MUP.


Importing Freud: first-wave psychoanalysis, interwar social sciences, and the interdisciplinary foundations of an American social theory.
For all that has been written about Freud, one of the most significant sites for his initial importation into the U.S. remains largely unexamined: namely, within and through the social sciences. During these early years, social scientists were attracted to psychoanalysis for reasons that were not only personal and idiosyncratic, but also intellectual, social, and professional. Focusing on the University of Chicago's Division of Social Sciences and using oral histories, students records, course materials, as well as published sources, this essay explores this varied attraction and its substantive impact upon American social theory vis-à-vis the ideals and ideology of "social adjustment."


A molecular photodiode system that can switch photocurrent direction.
We prepared a molecular photodiode system in which the photocurrent direction can be switched by choosing the wavelength of an irradiating light. The molecular system is composed of two types of helical peptides that carry different chromophores and have different directions of dipole moments when they are immobilized on gold. The mixed, self-assembled monolayer generated an anodic photocurrent when one of the two chromophores was photoexcited, whereas the photocurrent switched to being cathodic when the other chromophore was photoexcited. The opposite current response arises from the dipole moment of each helical peptide, which accelerates electron transfer in the same direction.


Clinical swallowing assessment in intensive care unit.
To report the results of the full clinical swallowing assessment in acute-care population in a large Brazilian teaching hospital. A prospective, descriptive clinical study was conducted during three months in a 30-bed adult clinical emergency ICU from a large Brazilian teaching hospital. Thirty-five patients consecutively referred to the Speech-Language Pathology Service according to our standard clinical practice were included. A full clinical swallowing assessment was completed and includes a Preliminary Assessment Protocol (PAP), a Dysphagia Risk Evaluation Protocol (DREP) and an Oral Feeding Transition Protocol (OFTP). In this study, the prevalence of OD in the ICU setting was of 63%, most of which were classified as moderate and moderate-severe (39%). Patients submitted to orotracheal intubation were very frequently referred to swallowing assessment (74%). The results of the statistical analyses revealed clinical indicators that could correctly classify patients as either having or not having OD on clinical tests. These include cough strength, coordination between breathing and speaking, dysphonia severity, and laryngeal elevation. Twenty six patients (74%) completed all protocols. Of these total, 38% were able to eat a regular diet. The practice with standardized protocols adds an important option for the management of oropharyngeal dysphagia in intensive care unit.


Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction.
The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.


The Francisella tularensis LVS ΔpdpC mutant exhibits a unique phenotype during intracellular infection.
A prerequisite for the virulence of the facultative intracellular bacterium Francisella tularensis is effective intramacrophage proliferation, which is preceded by phagosomal escape into the cytosol, and ultimately leads to host cell death. Many components essential for the intracellular life cycle are encoded by a gene cluster, the Francisella pathogenicity island (FPI), constituting a type VI secretion system. We characterized the FPI mutant ΔpdpC of the live vaccine strain (LVS) of F. tularensis and found that it exhibited lack of intracellular replication, incomplete phagosomal escape, and marked attenuation in the mouse model, however, unlike a phagosomally contained FPI mutant, it triggered secretion of IL-1β, albeit lower than LVS, and markedly induced LDH release. The phenotype of the ΔpdpC mutant appears to be unique compared to previously described F. tularensis FPI mutants.


Direct enzyme-linked immunosorbent assay that uses peroxidase-labeled antigen for determination of immunoglobulin M antibody to cytomegalovirus.
A direct enzyme-linked immunosorbent assay was developed for the measurement of immunoglobulin M (IgM) antibody to cytomegalovirus (CMV). Wells of microtiter plates were coated with anti-human IgM. Each patient's serum was added at a dilution of 1:100, and IgM from the serum was allowed to react with anti-human IgM. The amount of CMV-specific IgM antibody bound was determined by measuring the intensity of color change after the addition of peroxidase-labeled CMV antigen and substrate. Nuclei of infected cells served as an antigen source. CMV IgM could be detected only in IgM fractions of sera from patients with a recent CMV infection. Rheumatoid factor did not cause false-positive results. No cross-reactions were observed when paired sera from 22 patients with herpes simplex or varicella and single sera from 12 patients with suspected infectious mononucleosis were tested by the direct enzyme-linked immunosorbent assay. Each of 17 patients with a seroconversion for CMV antibody showed CMV-specific IgM antibody. In six of these patients the antibody was detected in the initial serum. The direct enzyme-linked immunosorbent assay for CMV IgM is a specific and sensitive test for the diagnosis of recent CMV infections and possesses distinct advantages over indirect tests.


[Dynamics of changes in the heparin-binding activity of rat brain proteins after fractionated exposure to ionizing radiation of low intensity].
In experiment on white rats it was shown that fractionated exposure to 1 sGy/day during 25 days is followed by the directed change in the total heparin-binding activity of proteins in the rat brain (both in males and in females) with maximum deviation from control by the 7th day after accumulation of a total dose of 25 sGy. The diverse in hemisphere cortex and hippocampus were different from those in brain trunk regions and cerebellum. It is supposed that a thin overturning of the intercellular and "cell-matrix" interactions in CNS modulates compensation and adaptation processes under chronic X-ray irradiation with a small dose of low intensity due to regulation of the free/bound heparansulphate correlation.


The Bandim TBscore--reliability, further development, and evaluation of potential uses.
The tuberculosis (TB) case detection rate has stagnated at 60% due to disorganized case finding and insensitivity of sputum smear microscopy. Of the identified TB cases, 4% die while being treated, monitored with tools that insufficiently predict failure/mortality. To explore the TBscore, a recently proposed clinical severity measure for pulmonary TB (PTB) patients, and to refine, validate, and investigate its place in case finding. The TBscore's inter-observer agreement was assessed and compared to the Karnofsky Performance Score (KPS) (paper I). The TBscore's variables underlying constructs were assessed, sorting out unrelated items, proposing a more easily assessable TBscoreII, which was validated internally and externally (paper II). Finally, TBscore and TBscoreII's place in PTB-screening was examined in paper III. The inter-observer variability when grading PTB patients into severity classes was moderate for both TBscore (κW=0.52, 95% CI 0.46-0.56) and KPS (κW=0.49, 95% CI 0.33-0.65). KPS was influenced by HIV status, whereas TBscore was unaffected by it. In paper II, proposed TBscoreII was validated internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a failure to bring down the score by ≥25% from baseline to 2 months of treatment predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and TBscoreII were assessed in health-care-seeking adults and found to be higher in PTB-diagnosed patients, 4.9 (95% CI 4.6-5.2) and 3.9 (95% CI 3.8-4.0), respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7-3.2) and 2.4 (95% CI 2.3-2.5), respectively. Had we referred only patients with cough >2 weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in our cohort. A TBscoreII>=2 missed 8.6%. TBscore and TBscoreII are useful monitoring tools for PTB patients on treatment, as they could fill the void which currently exists in risk grading of patients. They may also have a role in PTB screening; however, this requires our findings to be repeated elsewhere.


Beyond dialysis: current and emerging blood purification techniques.
Extracorporeal blood purification using various techniques and hardware is a major part of the modern day practice of clinical nephrology. Although the various modalities of hemodialysis and hemofiltration are the most commonly used extracorporeal therapies in clinical nephrology, blood purification using other techniques have become necessary to remove pathogenic, toxic, or waste substances not easily cleared by hemodialysis or hemofiltration due to factors such as molecular size, protein binding, and lipid solubility. The following review is an up to date summary of extracorporeal therapies, beyond hemodialysis and hemofiltration, in current clinical use as practiced by nephrologists and others in the United States and beyond. This comprises therapeutic apheresis (plasma exchange and cytapheresis), plasma adsorption, hemoperfusion, and the bio-artificial devices.


Efficacy and Safety of gonadotropin-releasing hormone (GnRH) Agonists Triptorelin Acetate and Cetrorelix Acetate in Assisted Reproduction.
BACKGROUND The aim of this study was to compare the efficacy and safety of 2 GnRH agonists - triptorelin acetate and cetrorelix acetate - in assisted reproduction. MATERIAL AND METHODS A total of 182 females who received in vitro fertilization and embryo transfer (IVF+ET) from March 2014 to July 2014 were involved, and their clinical data were retrospectively analyzed. Among them, 91 patients received treatment with short-acting triptorelin (group A) and another 91 patients were treated with cetrorelix acetate (group B). Fasting blood was extracted from each patient on the day of administration of human chorionic gonadotropin (hCG), and serum levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P) were detected using chemiluminescence method. The number of oocytes, fertilization rate, cleavage rate, and number of obtained embryos were recorded and compared. Pregnancy outcomes and adverse events were observed and compared. Expression level of FSH receptor (FSHR) in endometrial tissues was measured by qRT-PCR. RESULTS Serum level of E2 was significantly lower in group B than in group A (p<0.05). Indices, including the number of oocytes, fertilization rate and cleavage rate, number of obtained embryos, and pregnancy rate, were slightly better in group B than in group A, but no significant differences were found. The incidence of ovarian hyperstimulation syndrome (OHSS) was significant higher in group A than in group B (p<0.05). FSHR expression level was significantly lower in group B than in group A. CONCLUSIONS The effect of cetrorelix acetate is superior to that of short-acting triptorelin in assisted reproduction. Our most important finding is that cetrorelix acetate reduced the incidence of OHSS.


Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs.
Viral vectors have become the best option for the delivery of therapeutic genes in conventional and RNA interference-based gene therapies. The current viral vectors for the delivery of small regulatory RNAs are based on DNA viruses and retroviruses/lentiviruses. Cytoplasmic RNA viruses have been excluded as viral vectors for RNAi therapy because of the nuclear localization of the microprocessor complex and the potential degradation of the viral RNA genome during the excision of any virus-encoded pre-microRNAs. However, in the last few years, the presence of several species of small RNAs (e.g., virus-derived small interfering RNAs, virus-derived short RNAs, and unusually small RNAs) in animals and cell cultures that are infected with cytoplasmic RNA viruses has suggested the existence of a non-canonical mechanism of microRNA biogenesis. Several studies have been conducted on the tick-borne encephalitis virus and on the Sindbis virus in which microRNA precursors were artificially incorporated and demonstrated the production of mature microRNAs. The ability of these viruses to recruit Drosha to the cytoplasm during infection resulted in the efficient processing of virus-encoded microRNA without the viral genome entering the nucleus. In this review, we discuss the relevance of these findings with an emphasis on the potential use of cytoplasmic RNA viruses as vehicles for the efficient delivery of therapeutic small RNAs.


Cyproheptadine-induced depletion of insulin in the rat.
The pancreotoxicity of cyproheptadine (CPH) in rats was characterized through measurement of proinsulin and insulin levels in the pancreas as well as plasma immunoreactive insulin (IRI) and glucose levels at various times during and after drug treatment. Daily oral doses of CPH (45 mg/kg) depleted pancreatic IRI to 25% of control within 3 days. Pancreatic IRI levels showed no further decrease during the rest of a 2-week treatment period and returned to normal levels 2 days after withdrawal of the drug. Pancreatic proinsulin levels were not significantly changed by CPH treatment, and the decrease in pancreatic IRI can be ascribed primarily to a decrease in insulin. Nonfasting hyperglycemia was evident after two doses of CPH and persisted throughout the treatment period. Plasma IRI was not significantly altered compared to control and was inappropriately low for the hyperglycemia that was produced by CPH. Daily doses of CPH given i.p. (45 mg/kg) caused a transient decrease in pancreatic IRI, but hyperglycemia did not occur. Lower i.p. doses (22.5 mg/kg/day) caused a sustained decrease in pancreatic IRI content to 45% of control after 2 weeks and hyperglycemia was evident throughout the treatment period. No changes in pasma IRI were observed as a result of drug treatment even though blood glucose was elevated. These results suggest that biochemical changes affecting insulin synthesis and/or storage are associated with previously reported CPH-induced morphologic alterations in the rat beta-cell.


[Endoscopy combined hemostasis. Pathogenetic mechanisms of therapeutic action in gastroduodenal ulcers, complicated by severe blood loss and hemorrhagic shock].
On the basis of results of research the pathomorphology severe blood loss and haemorrhagic shock at 38 patients who have died from ulcer gastroduodenal of bleedings, with the purpose of preventive maintains of relapses of bleedings am established by authors necessity of carrying out of the general, and also local metabolic rehabilitation during the endoscopic haemostasis at massive bleedings at the patients with high risk of surgical treatment.


Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women.
Intra-individual variability for serum and urinary hormones has been inadequately considered in previous studies. Therefore, in the planning phase of a prospective study of Hormones and Diet in the Etiology of Breast Cancer (ORDET study), androgen levels have been examined at two different times in 56 women (26 in premenopause and 30 in postmenopause). Hormonal measurements in serum showed a good level of agreement for both premenopause (pre) and postmenopause (post): androstenedione pre r = 0.70 (p less than 0.0001), post r = 0.77 (p less than 0.0001); testosterone pre r = 0.73 (p less than 0.0001), post log values r = 0.74 (p less than 0.0001). Dihydrotestosterone showed a good level for premenopause only: log values pre r = 0.82 (p less than 0.0001), post r = 0.41 (p less than 0.05). Agreement levels in urine were inferior to those of serum: testosterone pre r = 0.53 (p less than 0.05), post r = 0.41 (p less than 0.05); androstanediol log values r = 0.46 (p less than 0.001), post log values r = 0.57 (p less than 0.05). Correlation between the two measurements improves considering age, parity, time of blood collection and, for urine, the interval of sample collections.


Prophylactic Anticonvulsants After Neurosurgery.
Six prospective, controlled trials have examined the effects of antiepileptic drugs (AEDs) given to prevent the occurrence of seizures following neurosurgery. Some studies have concentrated on specific reasons for the neurosurgery (brain tumor) while others have included people with a variety of indications for surgery. Phenytoin (PHT) has been studied most, but carbamazepine (CBZ) and phenobarbital (PB) have also been evaluated to some extent. Studies of people with traumatic brain injury (some of whom were operated on) provide some, but less direct, evidence of the prophylactic effects of AEDs after neurosurgery. Despite considerable variation in reasons for the neurosurgery, AEDs given, and study design, the overall conclusions are remarkably consistent. The seizure risk is reduced about 40%-50% for the first week after neurosurgery in those given the older AEDs compared with those given placebo or no treatment. After the first few weeks, none of the drugs has been proven to reduce the incidence of seizures and in most situations the best estimate is essentially no effect, but effects on the order of a 25%-50% reduction in late (epileptic) seizures cannot be ruled out. The new generation of AEDs have not been tested as prophylactic agents after neurosurgery. Although there are no guidelines for prophylaxis following neurosurgery in general, these results are consistent with the guidelines of professional organizations for subsets of neurosurgery cases. Those guidelines consider prophylaxis, especially using PHT, to be an option for the first week after surgery but that the routine use of prophylactic anticonvulsants after the first week is not warranted.


[Infections with Mycobacterium kansasii in the Academic Medical Center in Amsterdam: the changing clinical spectrum since the start of the HIV epidemic].
Inventory of patients with a Mycobacterium kansasii infection. Descriptive, retrospective. Academic Medical Centre, Amsterdam, the Netherlands. Review of the medical records of all patients with a bacteriologically confirmed infection with M. kansasii from January 1987 until the end of December 1996. M. kansasii was isolated from 17 patients. Of 15 HIV-tested patients 13 were seropositive. Their median CD4 count was 10 x 10(6)/l. Ten HIV-positive individuals used trimethoprim-sulfamethoxazole prophylaxis. In 1 HIV-seropositive and in 1 HIV-seronegative patient no chest X-rays were made. Caverns were present in none of 12 HIV-positive patients and in 1 of 3 HIV-negative patients. Of the HIV-positive patients 1 fulfilled the criteria for pulmonary infection of the American Thoracic Society (ATS). According to these criteria 9 of the HIV-positive patients were colonized with M. kansasii. In 6 of these patients there were indications of infection: regression of pulmonary infiltrates with therapy (n = 3), positive histology and culture of lung tissue at autopsy (n = 1), and dissemination (n = 2). Disseminated infection occurred in a total of 4 HIV-infected patients. HIV-infected patients are at an increased risk for M. kansasii infection. Trimethoprim-sulfamethoxazole does not offer protection against this infection. The diagnostic criteria of the ATS are not applicable to these patients. M. kansasii infection confirmed by isolation in an HIV-positive individual should always be treated.


Baicalin attenuates XRCC1-mediated DNA repair to enhance the sensitivity of lung cancer cells to cisplatin.
Baicalin plays important roles in different types of cancer. A previous report showed that baicalin attenuates cisplatin resistance in lung cancer. However, its mechanism remains unclear. In this study, we investigated the effect and mechanism of baicalin on DNA repair and sensitivity of lung cancer cells to cisplatin. A549 and A549/DPP cells were treated with baicalin and cisplatin. A549/DPP cells were transfected with XRCC1 and siXRCC1. Cell viability and DNA damage were detected by MTT and comet assay. Apoptosis rate and cell cycle were detected by flow cytometry assay. The expressions of Bax, Bcl-2, and Cyclin D1 were detected by western blot. XRCC1 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Baicalin and cisplatin decreased cell viability in A549 and A549/DPP cells in dose-dependent manner. Baicalin enhanced the effect of cisplatin on promoting apoptosis, arresting cell on S stage and triggering DNA damage accompanied with the upregulation of Bcl-2-associated X protein (Bax) and downregulation of B-cell lymphoma 2 (Bcl-2) and Cyclin D1 in A549/DPP cells. Moreover, baicalin promoted the inhibitory effect of cisplatin on XRCC1 expression in A549 and A549/DPP cells. However, the synthetic effects of baicalin and cisplatin on A549/DPP cells were partially inhibited by XRCC1 overexpression and promoted by XRCC1 knockdown. This study demonstrates that baicalin interferes with XRCC1-mediated cellar DNA repair to sensitize lung cancer cells to cisplatin.


Evaluation and applicability of predictive equations of the glomerular filtration rate in chronic kidney disease.
Prediction equations of glomerular filtration rate (GFR) may facilitate early detection, evaluation and management of chronic kidney disease (CKD). However, the reliability of these equations was not extensively studied in our CKD population. Hence, the present study was aimed to determine the performance of modification of diet in renal disease (MDRD) and Cock-croft Gault formulas in predicting GFR in CKD patients and their relationship with the measured GFR. A total of 104 subjects (71 male and 33 female, aged 26-68 years) with different stages of CKD were recruited for this study; we excluded 51 patients due to improper collection of 24-h urine. The GFR was measured using 24-h creatinine clearance and predicted by the Cockcroft Gault, the 4-variable MDRD and the 6-variable MDRD equations. Prediction equations correlated well with the measured GFR. However, the predicted GFR using the 4-variable MDRD equation revealed a highly significant positive correlation with the GFR measured by creatinine clearance (r = 0.86, P < 0.001), followed by the 6-variable MDRD and Cockcroft-Gault equations with r = 0.85 and 0.77, P < 0.001, respectively. In conclusion, the present study predicts that the 4-variable MDRD is the best available equation for predicting GFR in our CKD population.


Programmable and sequential Gaussian gates in a loop-based single-mode photonic quantum processor.
A quantum processor to import, process, and export optical quantum states is a common core technology enabling various photonic quantum information processing. However, there has been no photonic processor that is simultaneously universal, scalable, and programmable. Here, we report on an original loop-based single-mode versatile photonic quantum processor that is designed to be universal, scalable, and programmable. Our processor can perform arbitrarily many steps of programmable quantum operations on a given single-mode optical quantum state by time-domain processing in a dynamically controlled loop-based optical circuit. We use this processor to demonstrate programmable single-mode Gaussian gates and multistep squeezing gates. In addition, we prove that the processor can perform universal quantum operations by injecting appropriate ancillary states and also be straightforwardly extended to a multimode processor. These results show that our processor is programmable, scalable, and potentially universal, leading to be suitable for general-purpose applications.


Atomistic Mechanisms of Chemical Mechanical Polishing of a Cu Surface in Aqueous H2O2: Tight-Binding Quantum Chemical Molecular Dynamics Simulations.
We applied our original chemical mechanical polishing (CMP) simulator based on the tight-binding quantum chemical molecular dynamics (TB-QCMD) method to clarify the atomistic mechanism of CMP processes on a Cu(111) surface polished with a SiO2 abrasive grain in aqueous H2O2. We reveal that the oxidation of the Cu(111) surface mechanically induced at the friction interface is a key process in CMP. In aqueous H2O2, in the first step, OH groups and O atoms adsorbed on a nascent Cu surface are generated by the chemical reactions of H2O2 molecules. In the second step, at the friction interface between the Cu surface and the abrasive grain, the surface-adsorbed O atom intrudes into the Cu bulk and dissociates the Cu-Cu bonds. The dissociation of the Cu-Cu back-bonds raises a Cu atom from the surface that is mechanically sheared by the abrasive grain. In the third step, the raised Cu atom bound to the surface-adsorbed OH groups is removed from the surface by the generation and desorption of a Cu(OH)2 molecule. In contrast, in pure water, there are no geometrical changes in the Cu surface because the H2O molecules do not react with the Cu surface, and the abrasive grain slides smoothly on the planar Cu surface. The comparison between the CMP simulations in aqueous H2O2 and pure water indicates that the intrusion of a surface-adsorbed O atom into the Cu bulk is the most important process for the efficient polishing of the Cu surface because it induces the dissociation of the Cu-Cu bonds and generates raised Cu atoms that are sheared off by the abrasive grain. Furthermore, density functional theory calculations show that the intrusion of the surface-adsorbed O atoms into the Cu bulk has a high activation energy of 28.2 kcal/mol, which is difficult to overcome at 300 K. Thus, we suggest that the intrusion of surface-adsorbed O atoms into the Cu bulk induced by abrasive grains at the friction interface is a rate-determining step in the Cu CMP process.


TG-1: a marker for neuronal nuclei in Alzheimer's disease.
TG-1 is a monoclonal antibody (mAb) raised against paired helical filaments purified from Alzheimer's Disease (AD) brain by immunoaffinity chromatography. By immunocytochemistry, TG-1 reveals abundant staining of neuronal nuclei in AD brain, but little or no staining in normal brain. TG-1 stained nuclei are observed in areas of AD brain with neurofibrillary pathology and in certain neurones that are not normally affected. Biochemical studies with TG-1 show antigens of 32-38 kDa in pellets and 50 kDa in supernatants from brain, with no obvious differences between normal and AD. TG-1 also recognizes an unusual structure, i.e., a 'starburst' in brain tissue from AD and elderly normals. Starbursts are not immunoreactive for the astrocytic marker, glial fibrillary acidic protein, and are not associated with amyloid. Widespread nuclear staining is observed with TG-1 in rat brain, and the immunoreactive antigens in purified nuclei are similar to those in human brain. Thus, TG-1 identifies neuronal nuclear antigens that are altered in AD, and provides a new avenue for studying pathogenic mechanisms in the disease.


Navigating sexual health in cancer survivorship: a dyadic perspective.
This qualitative study examined how young adult breast cancer survivors (YABCS) and their partners appraised and managed their sexual health and intimate relationships after cancer. We conducted concurrent, individual telephone interviews with 25 YABCS and their male partners. We utilized a thematic, inductive analysis to examine individual interviews, followed by analysis within and across couples to identify dyadic themes. We explored how themes mapped on to the Theory of Dyadic Illness Management to build a conceptual model specific to the sexual health challenges of young adult couples living with cancer. Our analysis revealed five interconnected themes: (1) shared understanding of physical and psychological challenges of sexual health after cancer, (2) navigating role shifts and changes to sexual relationship, (3) getting through it as a team, (4) maintaining open communication, and (5) need for services and support for partners/caregivers and couples. Both survivors and their partners articulated physical (e.g., painful sex, decreased libido) and psychological (e.g., guilt, self-consciousness) challenges to their sexual health in survivorship. Our dyadic focus revealed a spectrum of ways that couples managed the changes to their relationships and sexual health, highlighting "open communication" and strategies for "working as a team" as critical. There is no "one size fits all" solution, as individuals and couples cope with and manage these challenges in different ways. Study results can inform couple-focused intervention strategies, such as creating shared understanding of sexual health after cancer and improving communication skills.


Relationship between nonperfusion area from widefield optical coherence tomography angiography and macular vascular parameters in diabetic retinopathy.
To evaluate the relationship between the nonperfusion area (NPA) from widefield optical coherence tomography angiography (OCTA) and macular vascular parameters in diabetic retinopathy (DR). In total, 51 eyes from 51 patients with proliferative DR (PDR) or moderate/severe non-PDR were included. Widefield OCTA using the Zeiss Plex Elite 9000 was performed. A semi-automatic algorithm calculated the percentages of the NPA within the total image. Macular OCTA (3 × 3 mm and 6 × 6 mm area) was scanned using the RTVue-XR Avanti. Vessel density (VD) was automatically separated into the superficial (SCP) and deep capillary plexus (DCP), and foveal avascular zone (FAZ) measurements were computed according to the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. A negative correlation was found between the average VD of the SCP and DCP obtained 3 × 3 mm and 6 × 6 mm area and the NPA. Multiple regression analysis revealed that the temporal-perifoveal region most negatively correlated with the NPA (r = - 0.55, p < 0.0001). No correlation was found between FAZ measurements and DR severity (area, p = 0.07; perimeter, p = 0.13). Diabetic macular nonperfusion was significantly associated with the NPA from widefield OCTA. In particular, the temporal-perifoveal DCP disorder may be a sensitive indicator of wide NPA.


Marker assisted genetic analysis of non-brittle rachis trait in barley.
Brittle rachis is a head shattering mechanism of barley. Two tightly linked complementary genes, btr1 and btr2, were believed to control the non-brittle rachis trait. Position of non-brittle rachis loci btr1btr2 on the short arm of Chromosome 3 was investigated using RFLP markers. Two approaches were employed. First, a Hordeum vulgare subsp. spontaneum fragment that confers brittleness in a cv. Bowman near isogenic line was detected. This fragment is 18-33 cM in length and contains MWG798B, ABG057, MWG014, BCD706 and KFP216 markers of the short arm of Chromosome 3. In the second approach, position of btr1 locus in a H. vulgare subsp. spontaneum (Wadi Qilt 23-38)xH. vulgare subsp. vulgare (cv. Harrington) cross was detected using a selective genotyping approach in BC2F1 generation. F-tests and analysis of genotypic compositions of BC2F1 lines showed that btr1 locus, and supposedly the tightly linked btr2 locus, is in 4.3 cM KFP216-RisP114 interval of short arm of Chromosome 3. Results also yielded clues for the presence of at least two additional loci that affect the non-brittle rachis trait. Allelism tests using genotypes with known non-brittle rachis gene compositions provided additional evidence for presence of such loci.


The role of activation functions 1 and 2 of estrogen receptor-α for the effects of estradiol and selective estrogen receptor modulators in male mice.
Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-α. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ERα had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ERα for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERαAF-1 (ERαAF-1(0)), ERαAF-2 (ERαAF-2(0)), or the total ERα (ERα(-/-)) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ERα(-/-) or ERαAF-2(0). However, the effects of E2 in orx ERαAF-1(0) [corrected] were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERαAF-1 for the effects of SERMs, we treated orx WT and ERαAF-1(0) mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERαAF-1(0) mice. In conclusion, ERαAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERαAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERαAF-1. Our findings might contribute to the development of bone-specific SERMs in males.


Critical periods for the effects of infantile experience on adult learning.
Mice were shocked with 0.1, 0.3, or 0.5 ma of current at 2 to 3, 8 to 9, or 15 to 16 days. Handled, nonshocked and nonhandled controls were also used. In adulthood each group was split into thirds and taught an avoidance response under shock of 0.3, 0.5, or 0.7 ma. The amount of shock given during infancy and adulthood, and the age at which shock occurred, were all found to have significant effects upon learning.


Alternative Lengthening of Telomeres and Differential Expression of Endocrine Transcription Factors Distinguish Metastatic and Non-metastatic Insulinomas.
Insulin-producing pancreatic neuroendocrine tumors (PanNETs)/insulinomas are generally considered to be indolent tumors with an excellent prognosis after complete resection. However, some insulinomas have a poor prognosis due to relapses and metastatic disease. Recently, studies in non-functional PanNETs indicated that behavior can be stratified according to alpha- and beta-cell differentiation, as defined by expression of the transcription factors ARX and PDX1, respectively. It is unknown whether similar mechanisms play a role in insulinomas. Therefore, we determined ARX and PDX1 expression in a cohort of 35 sporadic primary insulinomas and two liver metastases of inoperable primary insulinomas. In addition, WHO grade and loss of ATRX or DAXX were determined by immunohistochemistry, and alternative lengthening of telomeres (ALT) and CDKN2A status by fluorescence in situ hybridization. These findings were correlated with tumor characteristics and clinical follow-up data. In total, five out of 37 insulinoma patients developed metastatic disease. Metastatic insulinomas were all larger than 3 cm, whereas the indolent insulinomas were smaller (p value < 0.05). All three primary insulinomas that metastasized showed ARX expression, 2/3 showed ALT, and 1/3 had a homozygous deletion of CDKN2A as opposed to absence of ARX expression, ALT, or CDKN2A deletions in the 32 non-metastatic cases. The two liver metastases also showed ARX expression and ALT (2/2). The presence of ARX expression, which is usually absent in beta-cells, and genetic alterations not seen in indolent insulinomas strongly suggest a distinct tumorigenic mechanism in malignant insulinomas, with similarities to non-functional PanNETs. These observations may inform future follow-up strategies after insulinoma surgery.


Immunogenicity of whole cell and outer envelope leptospiral vaccines in hamsters.
The immunogenicity of leptospiral whole cell (WC) and outer envelope (OE) vaccines from virulent and avirulent strains was compared in hamsters. The 50% protective dose against death (PD(50D)) and kidney infection (PD(50K)) was evaluated for serotypes icterohaemorrhagiae, canicola, pomona, and grippotyphosa. The OE and WC of virulent strains possessed greater immunogenicity than the OE and WC of avirulent strains. More vaccine (<0.1 to 11.0 mug [dry weight] per hamster) was required for the PD(50K) than for the PD(50D) (<0.1 to 1.7 mug [dry weight] per hamster). The OE from virulent strains of these four serotypes plus hardjo were combined to form a pentavalent OE vaccine which proved to be satisfactory in immunogenic potency. Duration of immunity was not evaluated.


Dietary retinoic acid affects song maturation and gene expression in the song system of the zebra finch.
Vitamin A, an essential nutrient, is required in its acidic form (retinoic acid) for normal embryogenesis and neuronal development, typically within well-defined concentration ranges. In zebra finches, a songbird species, localized retinoic acid synthesis in the brain is important for the development of song, a learned behavior sharing significant commonalities with speech acquisition in humans. We tested how dietary retinoic acid affects the development of song behavior and the brain's system for song control. Supplemental doses of retinoic acid given to juveniles during the critical period for song learning resulted in more variable or plastic-like songs when the birds reached adulthood, compared to the normal songs of vehicle-fed controls. We also observed that several genes (brinp1, nrgn, rxr-alpha, and sdr2/scdr9) had altered levels of expression in specific nuclei of the song system when comparing the experimental and control diet groups. Interestingly, we found significant correlations between gene expression levels in nuclei of the anterior forebrain pathway (lMAN and area X) and the degree of variability in the recorded songs. We observed, however, no major morphological effects such as changes in the volumes of song nuclei. Overall, our results lend further support to a fundamental role of retinoic acid in song maturation and point to possible molecular pathways associated with this action. The data also demonstrate that dietary content of Vitamin A can affect the maturation of a naturally learned complex behavior.


Metabolome-scale de novo pathway reconstruction using regioisomer-sensitive graph alignments.
Recent advances in mass spectrometry and related metabolomics technologies have enabled the rapid and comprehensive analysis of numerous metabolites. However, biosynthetic and biodegradation pathways are only known for a small portion of metabolites, with most metabolic pathways remaining uncharacterized. In this study, we developed a novel method for supervised de novo metabolic pathway reconstruction with an improved graph alignment-based approach in the reaction-filling framework. We proposed a novel chemical graph alignment algorithm, which we called PACHA (Pairwise Chemical Aligner), to detect the regioisomer-sensitive connectivities between the aligned substructures of two compounds. Unlike other existing graph alignment methods, PACHA can efficiently detect only one common subgraph between two compounds. Our results show that the proposed method outperforms previous descriptor-based methods or existing graph alignment-based methods in the enzymatic reaction-likeness prediction for isomer-enriched reactions. It is also useful for reaction annotation that assigns potential reaction characteristics such as EC (Enzyme Commission) numbers and PIERO (Enzymatic Reaction Ontology for Partial Information) terms to substrate-product pairs. Finally, we conducted a comprehensive enzymatic reaction-likeness prediction for all possible uncharacterized compound pairs, suggesting potential metabolic pathways for newly predicted substrate-product pairs.


Euphorbia factor L2 suppresses the generation of liver metastatic ascites in breast cancer via inhibiting NLRP3 inflammasome activation.
Metastasis is the leading cause of death in patients with breast cancer, in part due to the lack of effective treatments. Euphorbia factor L2 (EFL2) is a diterpenoid extracted from Euphorbia lathyris L. seeds, which has attracted increasing attention in recent years due to its anticancer effect. However, the role and molecular mechanism of EFL2 in breast cancer liver metastasis remain unclear. In the present study, a breast cancer liver metastasis model was constructed and the effect of EFL2 on ascites generation in mice was examined. H&E staining detected inflammatory cells and tumor cells in the liver, small intestine and tumor tissues. Western blotting and reverse transcription‑quantitative PCR were used to detect the protein and mRNA expression of NLR family pyrin domain containing‑3 (NLRP3) and related molecules in tumor tissues. Immunohistochemistry was used to detect the levels of CD4 and CD8 T cells in tumor tissue and immunofluorescence was used to further detect the expression level of NLRP3. Finally, the aforementioned experiments were further verified by overexpressing NLPR3. It was found that EFL2 inhibited generation of ascites in the model in a dose‑dependent manner. Furthermore, EFL2 inhibited tumor cell metastasis and enhanced immune cell infiltration. Meanwhile, EFL2 dose‑dependently downregulated the mRNA and protein expression of NLRP3 and related molecules in the model, and overexpression of NLRP3 abolished these beneficial effects of EFL2. Taken together, the present experimental data suggested that EFL2 has a significant inhibitory effect on ascites of breast cancer liver metastasis in vivo, which may inhibit tumor cell metastasis by downregulating NLRP3 expression, providing an experimental basis for treating breast cancer metastasis.


Under- and over-estimation: a bi-directional mapping process between symbolic and non-symbolic representations of number?
Over the last 30 years, numerical estimation has been largely studied. Recently, Castronovo and Seron (2007) proposed the bi-directional mapping hypothesis in order to account for the finding that dependent on the type of estimation task (perception vs. production of numerosities), reverse patterns of performance are found (i.e., under- and over-estimation, respectively). Here, we further investigated this hypothesis by submitting adult participants to three types of numerical estimation task: (1) a perception task, in which participants had to estimate the numerosity of a non-symbolic collection; (2) a production task, in which participants had to approximately produce the numerosity of a symbolic numerical input; and (3) a reproduction task, in which participants had to reproduce the numerosity of a non-symbolic numerical input. Our results gave further support to the finding that different patterns of performance are found according to the type of estimation task: (1) under-estimation in the perception task; (2) over-estimation in the production task; and (3) accurate estimation in the reproduction task. Moreover, correlation analyses revealed that the more a participant under-estimated in the perception task, the more he/she over-estimated in the production task. We discussed these empirical data by showing how they can be accounted by the bi-directional mapping hypothesis (Castronovo & Seron, 2007).


Partial clamping of the infrahepatic inferior vena cava for blood loss reduction during anatomic liver resection: A prospective, randomized, controlled trial.
Anatomic liver resection often requires the exposure of the hepatic vein on its cut surface, and theoretically, lower central venous pressure aids in reducing blood loss. Therefore, we hypothesized that manipulating the central venous pressure by partially clamping the infrahepatic inferior vena cava might reduce blood loss during anatomic liver resection. Patients undergoing planned anatomic liver resections were allocated randomly to the partial infrahepatic inferior vena cava clamping or nonclamping groups. Hepatocellular carcinoma diagnosis was set as a stratifying factor because of underlying liver disease. The primary outcome was intraoperative blood loss. Secondary outcomes were intraoperative parameters and postoperative safety. We submitted the detailed protocol to the University Hospital Medical Information Network Clinical Trials Registry (Registration number: UMIN000007339 [http://www.umin.ac.jp.]). Between August 2011 and August 2015, 90 patients were allocated randomly. Both groups had comparable baseline characteristics. The central venous pressure was reduced from 6.0 to 3.0 mm Hg in the partial inferior vena cava clamping group without any complications (P < .001). Among all eligible patients, median values for total blood loss, blood loss during liver resection, and blood loss per transected area (nonclamping vs clamping groups) were 360 vs 350 mL (P = .19), 310 vs 250 mL (P = .045), and 4.9 vs 3.6 mL/cm2 (P = .15), respectively. However, among the subgroup of patients with hepatocellular carcinoma, these median values were 460 vs 290 mL (P = .06), 365 vs 217 mL (P = .007), and 5.2 vs 3.6 mL/cm2 (P = .03), respectively. Morbidities and laboratory data were comparable in both groups. Partial infrahepatic inferior vena cava clamping safely reduced central venous pressure and may reduce blood loss in patients with hepatocellular carcinoma when central venous pressure is >5 mm Hg at hepatic parenchymal transection.


[Successful lysis of a septic thrombosis of the superior vena cava using recombinant tissue-plasminogen activator].
Recombinant human tissue-type plasminogen activator (rt-PA) was successfully given via central vein to a 1.7 year old child with angiographically documented septic vena cava superior thrombosis Thrombolytic therapy with rt-PA was started with 0.2 mg/kg as a slow bolus injection followed by an infusion of 0.8 mg/kg over 60 min. rt-PA was applicated 12 hours after an urokinase bolus in a dosage of 8000 E/kg and heparin infusion of 500 E/kg/die. No clinical side effects or alterations in the plasmatic coagulation profile were noted. The prompt clinical response suggests that the use of rt-PA in thrombotic disease should be investigated further to establish efficacy, dosing guidelines, complication rates, and contraindications in childhood.


[Development and effect analysis of web-based instruction program to prevent elementary school students from safety accidents].
This study was aimed to develop a WBI(Web Based Instruction) program on safety for 3rd grade elementary school students and to test the effects of it. The WBI program was developed using Macromedia flash MX, Adobe Illustrator 10.0 and Adobe Photoshop 7.0. The web site was http://www.safeschool.co.kr. The effect of it was tested from Mar 24, to Apr 30, 2003. The subjects were 144 students enrolled in the 3rd grade of an elementary school in Gyungju. The experimental group received the WBI program lessons while each control group received textbook-based lessons with visual presenters and maps, 3 times. Data was analyzed with descriptive statistics, and chi2 test, t-test, and repeated measure ANOVA. First, the WBI group reported a longer effect on knowledge and practice of accident prevention than the textbook-based lessons, indicating that the WBI is more effective. Second, the WBI group was better motivated to learn the accident prevention lessons, showing that the WBI is effective. As a result, the WBI group had total longer effects on knowledge, practice and motivation of accident prevention than the textbook-based instruction. We recommend that this WBI program be used in each class to provide more effective safety instruction in elementary schools.


[Significance of daily hydroxyprolinuria in the early diagnosis of nephrosclerosis in patients with chronic pyelonephritis].
Studies of daily excretion of hydroxyproline with the urine in patients with chronic pyelonephritis (CP) showed manifest hyper-hydroxyprolinuria at the early stages of the disease, which augmented with the development of renal insufficiency. Measurement of hydroxyproline in the urine of CP patients is proposed as a test reflecting the renal connective tissue metabolism at the early stages of the disease. It can be used for assessing the activity of the sclerotic process in the kidneys of CP patients, for predicting the disease course and outcome, and, probably, for developing methods of adequate pathogenetic therapy based on biochemical monitoring. The method is noninvasive, sufficiently informative, and available for clinical diagnostic laboratories.


Multi-Omics Analysis Reveals Intricate Gene Networks Involved in Female Development in Melon.
Sexual differentiation is an important developmental phenomenon in cucurbits that directly affects fruit yield. The natural existence of multiple flower types in melon offers an inclusive structure for studying the molecular basis of sexual differentiation. The current study aimed to identify and characterize the molecular network involved in sex determination and female development in melon. Male and female pools separated by the F2 segregated generation were used for sequencing. The comparative multi-omics data revealed 551 DAPs and 594 DEGs involved in multiple pathways of melon growth and development, and based on functional annotation and enrichment analysis, we summarized four biological process modules, including ethylene biosynthesis, flower organ development, plant hormone signaling, and ubiquitinated protein metabolism, that are related to female development. Furthermore, the detailed analysis of the female developmental regulatory pathway model of ethylene biosynthesis, signal transduction, and target gene regulation identified some important candidates that might have a crucial role in female development. Two CMTs ((cytosine-5)-methyltransferase), one AdoHS (adenosylhomocysteinase), four ACSs (1-aminocyclopropane-1-carboxylic acid synthase), three ACOs (ACC oxidase), two ARFs (auxin response factor), four ARPs (auxin-responsive protein), and six ERFs (Ethylene responsive factor) were identified based on various female developmental regulatory models. Our data offer new and valuable insights into female development and hold the potential to offer a deeper comprehension of sex differentiation mechanisms in melon.


X-ray Dose Rate and Spectral Measurements during Ultrafast Laser Machining Using a Calibrated (High-Sensitivity) Novel X-ray Detector.
Ultrashort pulse laser machining is subject to increase the processing speeds by scaling average power and pulse repetition rate, accompanied with higher dose rates of X-ray emission generated during laser-matter interaction. In particular, the X-ray energy range below 10 keV is rarely studied in a quantitative approach. We present measurements with a novel calibrated X-ray detector in the detection range of 2-20 keV and show the dependence of X-ray radiation dose rates and the spectral emissions for different laser parameters from frequently used metals, alloys, and ceramics for ultrafast laser machining. Our investigations include the dose rate dependence on various laser parameters available in ultrafast laser laboratories as well as on industrial laser systems. The measured X-ray dose rates for high repetition rate lasers with different materials definitely exceed the legal limitations in the absence of radiation shielding.


Intraventricular streptokinase after intraventricular hemorrhage in newborn infants.
Hydrocephalus following intraventricular hemorrhage (IVH) is still one of the most serious complications of premature birth. Ventriculoperitoneal shunt surgery cannot be carried out early and permanent dependence on a shunt is associated with several serious complications. To determine whether intraventricular streptokinase after intraventricular hemorrhage reduces the risk of permanent shunt dependence, neurodevelopmental disability or death in neonates at risk of, or actually developing, post-hemorrhagic hydrocephalus (PHH). This form of therapy is based on the hypothesis that multiple blood clots in the CSF are the initial cause of post-hemorrhagic ventricular dilatation and lysis of clots could reopen the pathways of circulation and re-absorption of CSF. Pediatric, Neurosurgical and General Medical Journals were handsearched from 1976, as well as the Medline database. Personal contacts were used. One randomised trial evaluated intraventricular streptokinase in infants developing post-hemorrhagic ventricular dilatation. Details of patient selection, patient allocation and the interventions were extracted. The end-points examined were: ventriculoperitoneal shunt, death, meningitis, and secondary hemorrhage. When intraventricular streptokinse was compared with conservative management of post-hemorrhagic ventricular dilatation, the numbers of deaths and babies with shunt dependence were identical in both groups. No information on the effect of intraventricular streptokinase on disability is available. There is cause for concern about meningitis and secondary intraventricular hemorrhage but numbers are insufficient to quantify the risks. Intraventricular fibrinolytic therapy with streptokinase, given when post-hemorrhagic ventricular dilatation is established, cannot be recommended for neonates following IVH. A conservative approach with CSF drainage applied only to symptomatic raised intracranial pressure seems appropriate.


[Plastic surgery of the pharyngo-esophageal junction as a new method of the surgical treatment of achalasia of the upper esophageal sphincter].
Dramatic disorders of swallowing function of the central genesis (mostly because of cerebral circulatory disturbances) can be eliminated by surgery. Based on the first experience gained in this country with aphagia correction the author devised and employed a new method of surgical treatment--plasty of the pharyngoesophageal transition, providing beneficial short- and long-term results.


Sexual stage development of cryptosporidia in the Caco-2 cell line.
We used the spontaneously differentiated human intestinal epithelial cell line Caco-2 to develop an in vitro model of Cryptosporidium sp. infection. The mean cell infection rate was 3% +/- 2%. Asexual stages of cryptosporidia were observed on day 2 postinoculation. Transmission electron microscopy showed the presence of macrogametes at day 5. This cell line appears to be suited to the study of the mechanisms by which biological agents inhibit both sexual and asexual development of cryptosporidia.


An Extensible De-Identification Framework for Privacy Protection of Unstructured Health Information: Creating Sustainable Privacy Infrastructures.
The volume of unstructured health records has increased exponentially across healthcare settings. Similarly, the number of healthcare providers that wish to exchange records has also increased and, as a result, de-identification and the preservation of privacy features have become increasingly important and necessary. Governance guidelines now require sensitive information to be masked or removed yet this remains a difficult and often ad-hoc task, particularly when dealing with unstructured text. Annotators are typically used to identify such sensitive information but they may only be effective in certain text fragments. There is at present no hybrid, sustainable framework that aggregates different annotators together. This paper proposes a novel framework that leverages a combination of state-of-the-art annotators in order to maximize the effectiveness of the de-identification of health information.


Home advantage in sport: an overview of studies on the advantage of playing at home.
This review identifies the most likely causes of home advantage. The results of previous studies have identified 4 factors thought to be responsible for the home advantage. These can be categorised under the general headings of crowd, learning, travel and rule factors. From the accumulated evidence, rule factors were found to play only a minor role (in a limited number of sports) in contributing to home advantage. Studies investigating the effect of learning factors found that little benefit was to be gained from being familiar with the local conditions when playing at home. There was evidence to suggest that travel factors were responsible for part of the home advantage, provided the journey involved crossing a number of time zones. However, since high levels of home advantage are observed within countries where travel distances are not great. travel factors were not thought to be a major cause of home advantage. The evidence from studies investigating crowd factors appeared to provide the most dominant causes of home advantage. A number of studies provide strong evidence that home advantage increases with crowd size, until the crowd reaches a certain size or consistency (a more balanced number of home and away supporters), after which a peak in home advantage is observed. Two possible mechanisms were proposed to explain these observations: either (i) the crowd is able to raise the performance of the home competitors relative to the away competitors; or (ii) the crowd is able to influence the officials to subconsciously favour the home team. The literature supports the latter to be the most important and dominant explanation. Clearly, it only takes 2 or 3 crucial decisions to go against the away team or in favour of the home team to give the side playing at home the 'edge'.


Effect of High-Dose Vitamin D Supplementation on Upper Respiratory Tract Infection Symptom Severity in Healthy Children.
Observational studies support the role of vitamin D in reducing viral upper respiratory tract infection (URTI) symptom severity in adults and children. This study assessed whether wintertime high-dose vitamin D supplementation (2000 IU/day) reduces URTI symptom severity compared with standard-dose (400 IU/day) supplementation in preschool children. Secondary objectives were to assess effects of high-dose supplementation on outpatient physician visits, emergency department (ED) visits and antibiotic prescriptions for URTI. This was a secondary analysis of a multisite randomized clinical trial involving 703 healthy 1- to 5-year-old children in Toronto, Canada. High-dose or standard-dose oral vitamin D was randomly assigned for 1 winter season. For each URTI, parents completed symptom checklists based on the Canadian Acute Respiratory and Flu Scale. Symptom severity, frequency of outpatient visits, ED visits and antibiotic prescriptions for URTI between groups were analyzed using negative binomial regression. URTI symptom severity was not reduced in the high-dose vs. standard-dose group [incidence rate ratio (IRR) = 0.97; 95% confidence interval (CI): 0.76-1.23]. High-dose vitamin D did not decrease frequency of outpatient visits (IRR = 1.16; 95% CI: 0.84-1.60), ED visits (IRR = 1.17; 95% CI: 0.57-2.40) or antibiotic prescriptions (IRR=1.02; 95% CI: 0.61-1.72). Serum 25-hydroxyvitamin D was higher in the high-dose group (48.7 ng/mL; 95% CI: 46.9-50.5) than the standard-dose group (36.8 ng/mL; 95% CI: 35.4-38.2; P < 0.001). High-dose vitamin D supplementation did not reduce URTI symptom severity, outpatient visits, ED visits or antibiotic prescriptions relative to standard-dose. These results do not support vitamin D supplementation above the standard recommended dose for reducing URTI symptoms in children.


Electron microscope tomography: transcription in three dimensions.
Three-dimensional reconstruction of an asymmetric biological ultrastructure has been achieved by tomographic analysis of electron micrographs of sections tilted on a goniometer specimen stage. Aligned micrographs could be displayed as red-green three-dimensional movies. The techniques have been applied to portions of in situ transcription units of a Balbiani ring in the polytene chromosomes of the midge Chironomus tentans. Current data suggest a DNA compaction of about 8 to 1 in a transcription unit. Nascent ribonucleoprotein granules display an imperfect sixfold helical arrangement around the chromatin axis.


hMuLab: A Biomedical Hybrid MUlti-LABel Classifier Based on Multiple Linear Regression.
Many biomedical classification problems are multi-label by nature, e.g., a gene involved in a variety of functions and a patient with multiple diseases. The majority of existing classification algorithms assumes each sample with only one class label, and the multi-label classification problem remains to be a challenge for biomedical researchers. This study proposes a novel multi-label learning algorithm, hMuLab, by integrating both feature-based and neighbor-based similarity scores. The multiple linear regression modeling techniques make hMuLab capable of producing multiple label assignments for a query sample. The comparison results over six commonly-used multi-label performance measurements suggest that hMuLab performs accurately and stably for the biomedical datasets, and may serve as a complement to the existing literature.


Influence of bilirubin on surface tension properties of lung surfactant.
To investigate the influence of bilirubin on the surface tension activity of a porcine derived (Curosurf) and synthetic (Exosurf) surfactant. The captive bubble surfactometer at phospholipid doses of 0.5 mg/ml (low dose) and 1 mg/ml (high dose) in solutions of increasing bilirubin concentrations (0.25, 0.5, and 1.0 mg/ml) was used. Curosurf (without bilirubin) showed a higher surface f1p4ion activity than Exosurf, as shown by area compression of 30 (SD 0.6)% compared with 76(1.4)% at low surfactant dose and 25 (0.9)% compared with 85 (0.5)% at high dose (P < 0.01). Bilirubin showed negligible surface activity at the concentrations studied. At low phospholipid dose (0.5 mg/ml Curosurf), bilirubin increased film area compression of lipid extract surfactant from 30 (0.6)% to 55 (1.6)%, 59 (0.1)%, and 68 (0.5)% at the three studied bilirubin concentrations, respectively (P < 0.01). At high phospholipid dose (1 mg/ml Curosurf), bilirubin had the same adverse, although less pronounced, effect on film area compression of porcine lipid extract surfactant (25 (0.9)% vs 26 (0.9)%, 39 (1.3)%, and 44 (1.1)%, respectively) (P < 0.01). Using synthetic surfactant (Exosurf), with a much lower original surface activity, bilirubin did not further inhibit its surface tension properties at any of the phospholipid doses studied. These results indicate that in vitro bilirubin impairs the surface tension activity of porcine lipid extract surfactant, but does not affect synthetic surfactant activity.


The correlation between carotid artery atherosclerosis and clinical ischemic heart disease in lupus patients.
The extent of subclinical atherosclerosis can be assessed by ultrasound measurement of carotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigate the correlation between measures of atherosclerosis as documented on imaging studies of the carotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythematosus (SLE). The study patients were recruited from the University of Toronto prospective cohort of SLE patients. Patients who had a history of CAD were compared to those without CAD. TPA and cIMT were measured using high-resolution optimized ultrasound systems. Logistic regression models were used to investigate the strength of association between ultrasound measures of atherosclerosis and CAD. The strength of association as expressed by odds ratio (OR) was compared between TPA and cIMT. A total of 103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlated only moderately with TPA (r = 0.43, p < 0.001). Both measures were significantly associated with the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55 vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hypertension compared to cIMT. In SLE patients, cIMT correlates only moderately with TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA correlated better than cIMT with cardiovascular risk factors and CAD, suggesting that it may serve as a better tool for the investigation of atherosclerosis in SLE.


Insulin does not act by causing a change in membrane potential or intracellular free sodium and potassium concentration of adipocytes.
The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, and the resting membrane potential were made using ion-selective and conventional microelectrodes. The use of these microelectrodes enabled us to continuously monitor these parameters in the same cell before, during, and after periods of insulin stimulation of up to 20-min duration. The electrical potentials measured in these experiments remained unchanged when the cells were stimulated with insulin (0.01, 0.1, or 1.0 mU/ml). Varying the extracellular glucose concentration had no effect on these results. Our results provide the first direct measurement of [Na+]i and [K+]i in adipose tissue and clearly demonstrate that the response to insulin's association with its receptors on the cell surface and subsequent action on hexose transport and cellular metabolism does not involve a change in membrane potential or intracellular sodium and potassium ions.


Improving Identification of Patients at Low Risk for Major Cardiac Events After Noncardiac Surgery Using Intraoperative Data.
Risk-stratification tools for cardiac complications after noncardiac surgery based on preoperative risk factors are used to inform postoperative management. However, there is limited evidence on whether risk stratification can be improved by incorporating data collected intraoperatively, particularly for low-risk patients. We conducted a retrospective cohort study of adults who underwent noncardiac surgery between 2014 and 2018 at four hospitals in the United States. Logistic regression with elastic net selection was used to classify in-hospital major adverse cardiovascular events (MACE) using preoperative and intraoperative data ("perioperative model"). We compared model performance to standard risk stratification tools and professional society guidelines that do not use intraoperative data. Of 72,909 patients, 558 (0.77%) experienced MACE. Those with MACE were older and less likely to be female. The perioperative model demonstrated an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI, 0.85-0.92). This was higher than the Lee Revised Cardiac Risk Index (RCRI) AUC of 0.79 (95% CI, 0.74-0.84; P < .001 for AUC comparison). There were more MACE complications in the top decile (n = 1,465) of the perioperative model's predicted risk compared with that of the RCRI model (n = 58 vs 43). Additionally, the perioperative model identified 2,341 of 7,597 (31%) patients as low risk who did not experience MACE but were recommended to receive postoperative biomarker testing by a risk factor-based guideline algorithm. Addition of intraoperative data to preoperative data improved prediction of cardiovascular complication outcomes after noncardiac surgery and could potentially help reduce unnecessary postoperative testing.


Enantiomerically enriched, polycrystalline molecular sieves.
Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. Enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electron microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).


Expression in plants of two bacterial antibiotic resistance genes after protoplast transformation with a new plant expression vector.
Two bacterial antibiotic resistance genes, one coding for the neomycin phosphotransferase (NPT I) from Tn903, and the other coding for the chloramphenicol acetyltransferase from Tn9 were used as plant selectable markers. Both genes were introduced into the Nicotiana tabacum genome in a new plant expression vector, using the direct gene transfer method. The vector pDH51, used in these experiments contains a plant expression unit as a movable cassette, consisting of the strong cauliflower mosaic virus (CaMV) 35S RNA promoter and transcription terminator separated by a polylinker containing several unique restriction sites.


Familial Cancers of Head and Neck Region.
Cancers that occur in families more often than would be expected by chance are termed as familial cancers. They occur due to an inherited genetic mutation and account for 5%-10% of all cancers. This review article presents some of the common Familial Cancer Syndromes (FCS) such as MEN 2B, hyperparathyroidism-jaw tumour syndrome, familial oral squamous cell carcinoma, melanoma, nasopharyngeal carcinoma, paraganglioma, neurofibroma and other syndromes associated with head and neck region.


Circulation immune complexes after renal transplantation.
The liquid phase C1q-binding assay was used as a measure of circulating immune complexes in 147 renal transplant recipients. Thirty-six patients were studied serially from the time of transplantation. Abnormal levels of C1q-binding activity (C1qBA) were most frequently detected in the first 6 months post-transplant. Although there was a statistically significant association of elevated C1qBA with rejection, the incidence of "false positives" and "false negatives" was high and particularly evident in serial studies. There was no evidence of association between C1qBA and the recipients' original renal diseases. Post-transplant monitoring of renal transplant recipients for circulating immune complexes by the C1q-binding assay is an unreliable guide to rejection.


Spatial memory deficits after vincristine-induced lesions to the dorsal hippocampus.
Vincristine is a commonly used cytostatic drug for the treatment of leukemia, neuroblastoma and lung cancer, which is known to have neurotoxic properties. The aim of this study was to assess the effects of vincristine, injected directly into the dorsal hippocampus, in spatial memory using the spatial cone field discrimination task. Long Evans rats were trained in the cone field, and after reaching training criterion received bilateral vincristine infusions into the dorsal hippocampus. Vincristine-treated animals presented unilateral or bilateral hippocampal lesions. Animals with bilateral lesions showed lower spatial working and reference memory performance than control animals, but task motivation was unaffected by the lesions. Working and reference memory of animals with unilateral lesions did not differ from animals with bilateral lesions and control animals. In sum, intrahippocampal injection of vincristine caused profound tissue damage in the dorsal hippocampus, associated with substantial cognitive deficits.


Diazepam and tests of thyroid function.
The effect of diazepam on thyroid function tests was examined in 12 euthyroid patients requiring the drug for psychiatric reasons and in six patients with thyrotoxicosis. Assessment was made before and after four weeks' therapy.There was no significant difference in results from tests of thyroid iodide trapping and binding (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) except in the one-hour thyroid uptake in the euthyroid group, which was increased after diazepam. This increase occurred without alteration in serum thyroid stimulating hormone levels. No change occurred in either group in tests of thyroid hormone release (protein-bound iodine, T-3 resin uptake, or Thyopac-3 and free thyroxine index).Patients with suspected thyroid disease who are taking diazepam do not need to stop therapy while their thyroid status is being determined.


On the size of ions solvated in helium clusters.
Helium nanodroplets are doped with SF(6), C(4)F(8), CCl(4), C(6)H(5)Br, CH(3)I, and I(2). Upon interaction with free electrons a variety of positively and negatively charged cluster ions X(+/-)He(n) are observed where X(+/-) = F(+/-), Cl(+/-), Br(+/-), I(+), I(2) (+), or CH(3)I(+). The yield of these ions versus cluster size n drops at characteristic sizes n(s) that range from n(s) = 10.2+/-0.6 for F(+) to n(s) = 22.2+/-0.2 for Br(-). n(s) values for halide anions are about 70% larger than for the corresponding cations. The steps in the ion yield suggest closure of the first solvation shell. We propose a simple classical model to estimate ionic radii from n(s). Assuming the helium density in the first solvation shell equals the helium bulk density one finds that radii of halide anions in helium are nearly twice as large as in alkali halide crystals, indicating the formation of an anion bubble due to the repulsive forces that derive from the exchange interaction. In spite of the simplicity of our model, anion radii derived from it agree within approximately 10% with values derived from the mobility of halide anions in superfluid bulk helium, and with values computed by quantum Monte Carlo methods for X(-)He(n) cluster anions.


Genetic mosaicism in basal cell carcinoma.
Human basal cell cancer (BCC) shows unique growth characteristics, including a virtual inability to metastasize, absence of a precursor stage and lack of tumour progression. The clonal nature of BCC has long been a subject for debate because of the tumour growth pattern. Despite a morphologically multifocal appearance, genetic analysis and three-dimensional reconstructions of tumours have favoured a unicellular origin. We have utilized the X-chromosome inactivation assay in order to examine clonality in 13 cases of BCC. Four parts of each individual tumour plus isolated samples of stroma were analysed following laser-assisted microdissection. In 12/13 tumours, the epithelial component of the tumour showed a monoclonal pattern suggesting a unicellular origin. Surprisingly, one tumour showed evidence of being composed of at least two non-related monoclonal clones. This finding was supported by the analysis of the ptch and p53 gene. Clonality analysis of tumour stroma showed both mono- and polyclonal patterns. A prerequisite for this assay is that the extent of skewing is determined and compensated for in each case. Owing to the mosaic pattern of normal human epidermis, accurate coefficients are difficult to obtain; we, therefore, performed all analyses both with and without considering skewing. This study concludes that BCC are monoclonal neoplastic growths of epithelial cells, embedded in a connective tissue stroma at least in part of polyclonal origin. The study results show that what appears to be one tumour may occasionally constitute two or more independent tumours intermingled or adjacent to each other, possibly reflecting a local predisposition to malignant transformation.


Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog.
In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 micrograms/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.


Comparative proteome and phosphoproteome analyses during cyprid development of the barnacle Balanus (=Amphibalanus) amphitrite.
The barnacle Balanus amphitrite (=Amphibalanus amphitrite) is a major marine biofouling invertebrate worldwide. It has a complex life cycle during which the larva (called a nauplius) molts six times before transforming into the cyprid stage. The cyprid stage in B. amphitrite is the critical stage for the larval decision to attach and metamorphose. In this study, proteome and phosphoproteome alterations during cyprid development/aging and upon treatment with the antifouling agent butenolide were examined with a two-dimensional electrophoresis (2-DE) multiplexed fluorescent staining approach. Optimized protein separation strategies, including solution-phase isoelectric fractionation and narrow-pH-range 2-DE, were used in a proteomic analysis. Our results show that the differential regulation of the target proteins is highly dynamic on the levels of both protein expression and posttranslational modification. Two groups of proteins, stress-associated and energy metabolism-related proteins, are differentially expressed during cyprid development. Comparison of the control and treatment groups suggests that butenolide exerts its effects by sustaining the expression levels of these proteins. Altogether, our data suggest that proteins involved in stress regulation and energy metabolism play crucial roles in regulating larval attachment and metamorphosis of B. amphitrite.


[Meteopathogenic mechanisms of exacerbating ischemic heart disease in an arid zone].
In arid zone of Uzbekistan summer heat discomfort aggravates the course of ischemic heart disease, provokes meteopathic reactions which we call "meteorological strain syndrome". In this season anginal attacks, episodes of arrhythmia and coronary failure become more frequent especially in patients over 70 years of age and migrants.


Embryonic lethality and defective neural tube closure in mice lacking squalene synthase.
Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/-) were apparently normal. SS+/- mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver and testis. Nevertheless, the hepatic cholesterol synthesis was not different between SS+/- and SS+/+ mice, and plasma lipoprotein profiles were not different irrespective of the presence of the low density lipoprotein receptor, indicating that SS is not a rate-limiting enzyme in the cholesterol biosynthetic pathway. The mice homozygous for the disrupted SS gene (SS-/-) were embryonic lethal around midgestation. E9.5-10.5 SS-/- embryos exhibited severe growth retardation and defective neural tube closure. The lethal phenotype was not rescued by supplementing the dams either with dietary squalene or cholesterol. We speculate that cholesterol is required for the development, particularly of the nervous system, and that the chorioallantoic circulatory system is not mature enough to supply the rapidly growing embryos with maternal cholesterol at this developmental stage.


State-of-the-Art Capability of Convolutional Neural Networks to Distinguish the Signal in the Ionosphere.
Recovering and distinguishing different ionospheric layers and signals usually requires slow and complicated procedures. In this work, we construct and train five convolutional neural network (CNN) models: DeepLab, fully convolutional DenseNet24 (FC-DenseNet24), deep watershed transform (DWT), Mask R-CNN, and spatial attention-UNet (SA-UNet) for the recovery of ionograms. The performance of the models is evaluated by intersection over union (IoU). We collect and manually label 6131 ionograms, which are acquired from a low-latitude ionosonde in Taiwan. These ionograms are contaminated by strong quasi-static noise, with an average signal-to-noise ratio (SNR) equal to 1.4. Applying the five models to these noisy ionograms, we show that the models can recover useful signals with IoU > 0.6. The highest accuracy is achieved by SA-UNet. For signals with less than 15% of samples in the data set, they can be recovered by Mask R-CNN to some degree (IoU > 0.2). In addition to the number of samples, we identify and examine the effects of three factors: (1) SNR, (2) shape of signal, (3) overlapping of signals on the recovery accuracy of different models. Our results indicate that FC-DenseNet24, DWT, Mask R-CNN and SA-UNet are capable of identifying signals from very noisy ionograms (SNR < 1.4), overlapping signals can be well identified by DWT, Mask R-CNN and SA-UNet, and that more elongated signals are better identified by all models.


Evaluation of ECG criteria for left ventricular hypertrophy before and after aortic valve replacement using magnetic resonance imaging.
Evaluation of different electrocardiographic criteria for left ventricular hypertrophy (ECG-LVH criteria) using left ventricular mass index (LVMI) determined by magnetic resonance imaging (MRI). In addition, the relation between LVMI regression after aortic valve replacement and corresponding ECG changes regarding LVH was studied. A group of 31 patients with severe aortic valve disease was studied to assess the presence of ECG-LVH and to measure LVMI and LV end-diastolic volume index (LVEDVI); 13 patients were restudied at 9.8 +/- 2.7 months after aortic valve replacement. Three criteria had a sensitivity of 100% (SV1 + RV5 or RV6 > 3.0 mV; SV1 or SV2 + RV5 > or = 3.5 mV; SV1 or SV2 + RV5 or RV6 > 3.5 mV), at the cost of specificity (50%, 44.4% and 44.4%, respectively). The R in I > 1.4 mV had a specificity of 100%, at the cost of both sensitivity and accuracy (13.6% and 54.5%, respectively). The Romhilt-Estes point score system, using > or = 4 points as cut-off value for LVH, provided the overall best accuracy of 79.5%. The number of Romhilt-Estes points also showed the best correlation with LVMI, both before and after aortic valve replacement (r = 0.81 and r = 0.67, respectively). Substantial differences in sensitivity, specificity, accuracy, and correlation with LVMI were found among several ECG-LVH criteria. No single criterion performed optimally since the highest sensitivity, specificity, accuracy, and correlation with LVMI were found with different criteria. The present study may therefore contribute to a more targeted use of the existing ECG-LVH criteria.