Erythrocyte and platelet volume in human hypertension. The Gubbio Study Collaborative Group.
It has been reported that in rat and human hypertension the erythrocyte volume is reduced while platelet volume is increased. Data from the Gubbio Study, a population-based study involving over 5000 people (response rate greater than 84%), were analysed in order to address this issue among adult participants. The erythrocyte volume was significantly greater in male and female hypertensives compared with sex-matched normotensives. Female hypertensives also had a slightly but significantly reduced platelet volume while no significant difference in platelet volume was found between male hypertensives and male normotensives. Contrary to data from previous clinical studies based on small series of patients and controls, the findings of this study indicate a positive association between hypertension and erythrocyte volume.


[The influence of Mycoplasma salivarium in the absence and presence of L-arginine on karyotypic variability in cell line of the Indian muntjak skin fibroblasts under long-term cultivation].
The influence of Mycoplasma salivarium on the numerical and structural karyotypic variability has been investigated in the "markerless" cell line of the Indian muntjak skin fibroblasts (line M) during long-term cultivation in the absence and presence of L-arginine. Cultivation of the mycoplasmal contaminated cells for 15 and 30 days did not change the character of cell distribution for the chromosome number. In the contaminated cells cultivated for 60 and 75 days, the character of cell distribution for the chromosome number was changed. These changes involved bimodal distribution for the chromosome number due to a significant decrease in the frequency of the cells with the modal number of chromosomes with main structural variant of karyotype (SVK)--2 + 2 + 1 + 1 + 1 and an increase in the frequency of cells with submodal number of chromosomes with main SVK--2 + 2 + 1 + 1. Besides, a significant increase in the frequency of the cells with lower chromosome number was observed in 60 days compared to that in 75 days of cultivation. Cultivation of the contaminated and control cells in the medium with increased concentration of L-arginine during 60 days did not change the numerical parameters relative to the control. Cultivation of the contaminated cells for 60 days followed by addition of L-arginine for 15 days restored the numerical parameters the numerical parameters to the control level. In the contaminated cells the frequency of chromosomal aberrations significantly increased for 30, 60 and 75 days cultivation relative to the control variant. In 30 days, the small but significant increase took place due to increase in the frequency of chromosomal aberrations of all the types. In 60 and 75 days, a greater increase took place due to a significant increase in the frequency of chromosomal and chromatid breaks. Moreover, in 60 days, the level of dicentrics (telomeric associations) mainly produced by chromosomes 1 and 2 increased significantly. The role of dicentrics as one of the ways for adaptation of the "markerless" cell lines to condition of cultivation and the role of L-arginine in the restoration of normal karyotypic structure of cell population of line M under mycoplasmal contamination are discussed.


Electron attachment to C2 fluorocarbon radicals at high temperature.
Thermal electron attachment to the radical species C2F3 and C2F5 has been studied over the temperature range 300-890 K using the Variable Electron and Neutral Density Attachment Mass Spectrometry technique. Both radicals exclusively undergo dissociative attachment to yield F(-). The rate constant for C2F5 shows little dependence over the temperature range, remaining ~4 × 10(-9) cm(3) s(-1). The rate constant for C2F3 attachment rises steeply with temperature from 3 × 10(-11) cm(3) s(-1) at 300 K to 1 × 10(-9) cm(3) s(-1) at 890 K. The behaviors of both species at high temperature are in agreement with extrapolations previously made from data below 600 K using a recently developed kinetic modeling approach. Measurements were also made on C2F3Br and C2F5Br (used in this work as precursors to the radicals) over the same temperature range, and, for C2F5Br as a function of electron temperature. The attachment rate constants to both species rise with temperature following Arrhenius behavior. The attachment rate constant to C2F5Br falls with increasing electron temperature, in agreement with the kinetic modeling. The current data fall in line with past predictions of the kinetic modeling approach, again showing the utility of this simplified approach.


• On reading 'A nurse's place...', I was incensed. I was shocked to think we had such small-minded, uninformed and sexist members of our profession. I was therefore relieved to note that the author was not a nurse, but a consultant surgeon.


Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis.
Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in hepatic fibrosis pathogenesis. Epithelial-mesenchymal transition (EMT), another vital participant in liver fibrosis, has the potential to initiate HSC activation, which promotes abundant myofibroblast production. Previous studies suggest that Enhancer of Zeste Homolog 2 (EZH2) plays a significant role in myofibroblast transdifferentiation; however, the underlying mechanisms remain largely unaddressed. Carnosol (CS), a compound extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the signaling mechanisms underlying EZH2 inhibition and the anti-fibrotic effect of CS in liver fibrosis. We found that CS significantly inhibited CCl4- and TGFβ1-induced liver fibrosis and reduced both HSC activation and EMT. EZH2 knockdown also prevented these processes induced by TGFβ1 in HSCs and AML-12 cells. Interestingly, the protective effect of CS was positively associated with Sirtuin 1 (SIRT1) activation and accompanied by EZH2 inhibition. SIRT1 knockdown attenuated the EZH2 inhibition induced by CS and increased EZH2 acetylation, which enhanced its stability. Conversely, upon TGFβ1 exposure, SIRT1 activation significantly reduced the level of EZH2 acetylation; however, EZH2 overexpression prevented the SIRT1 activation that primed myofibroblast inhibition, indicating that EZH2 is a target of SIRT1. Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Together, this study provides evidence of activation of the SIRT1/EZH2 pathway by CS that inhibits myofibroblast generation, and thus, CS may represent an attractive candidate for anti-fibrotic clinical therapy.


Changes of urinary steroid conjugates and gonadotropin excretion in the menstrual cycle and pregnancy in the Yunnan snub-nosed monkey (Rhinopithecus bieti).
The Yunnan snub-nosed monkey (Rhinopithecus bieti) is one of the most endangered species in the world, and it is endemic to China. According to our knowledge, there was no information on reproduction for this species. The present study was designed to understand the characteristics of reproductive hormone secretion during the menstrual cycle and pregnancy of this species by monitoring urinary estrone conjugate (E1C), pregnanediol-3-glucuronide (PdG), bioactive follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The urine samples were collected each day from four adult females for eight menstrual cycles, and once in 3 days during pregnancy (three full-term pregnancies, one mid-term abortion). The steroid conjugate was tested by radioimmunoassays (RIAs), and bioactive FSH and LH levels were measured in vitro by the sensitive bioassays granulosa cell aromatize bioassay (GAB) and rat interstitial cell testosterone (RICT), respectively. The results showed that: 1) E1C presented a preovulatory peak (183.9 +/- 8.6 ng/mgCr) followed by a definite elevation of PdG; 2) PdG in the luteal phase (754.4 +/- 30.6 ng/mgCr) was three- to fivefold higher than during the corresponding follicular phase (198.3 +/- 11.4 ng/mgCr); 3) the peaks of bio-LH and bio-FSH were on the same day, while the E1C peak was 1 or 2 days before the peaks for these two hormones; 4) bio-FSH levels were higher in the follicular phase than in the luteal phase, and bio-LH levels elevated slightly in the luteal phase; 5) the mean cycle length was 23.6 +/- 3.5 days (n = 3) based upon successive urinary LH peaks; 6) based on the interval from the day of E1C peak to the day of parturition, the gestation was 203.7 +/- 2.5 days (n = 3); and 7) both E1C and PdG increased and remained high after pregnancy, with a sharp decrease in basal levels following parturition or mid-term abortion. The results suggested that the pattern of reproductive hormones for R. bieti is similar to that of other Old World monkeys, but the concentration of the hormones is different from that of other species. This species has a longer progestation period, which may be related to its classification status.


A pitfall in ligation of intrahepatic shunting after Fontan type operation.
An 8-year-old boy experienced progressive cyanosis after a Fontan type operation. Under the guidance of intraoperative color Doppler we performed a transabdominal ligation of the accessory hepatic veins which drained into a common atrium. Reoperation was needed through a median sternotomy to eliminate residual shunting. Although intraoperative Doppler is useful to aid in the ligation of accessory veins while portal hypertension is monitored, intraoperative angiogram serves better to ensure the elimination of intrahepatic shunting in a transabdominal approach.


Crithidia fasciculata as feeder cells for malaria parasites.
Crithidia fasciculata was used to replace murine peritoneal wash cells as feeder cells for the adaptation of Plasmodium falciparum isolates to continuous culture in vitro, thus avoiding the need to sacrifice animals. Fourteen of 17 malaria parasite isolates in one study, and 12 of 12 isolates in a second study, were successfully adapted to continuous culture in the presence of C. fasciculata, while only 5 of 17 parallel control isolates in the first study, and 2 of 12 isolates in the second study, were adapted in the absence of any feeder cells. Biochemical assays were performed to investigate various hypotheses put forward to explain the mode of action of feeder cells. No effect of C. fasciculata feeder cells was observed on lactate removal, osmotic pressure, or glucose or amino acid content of the malaria culture media. This feeder cell system was shown to reduce the pH of the malaria culture medium. Neither this feeder system nor another system, murine peritoneal macrophages, had any effect on the cysteine content of the culture medium. C. fasciculata was shown to reduce the redox potential of the culture medium, as were other malaria growth enhancers including cysteine and glutathione. This effect on the redox potential of the culture medium is proposed to be a possible mode of action for the feeder cell systems studied.


The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner.
The acute release of neutrophils from the bone marrow is a critical step in their trafficking to sites of inflammation. This process is stimulated by systemically acting inflammatory mediators, such as the CXC chemokines. In this study we have used a novel in situ perfusion system of the rat femoral bone marrow to directly investigate the role of specific adhesion molecules in chemokine-stimulated neutrophil mobilization. We show here that neutrophils mobilized in response to rat macrophage inflammatory protein-2 (MIP-2) shed L-selectin and expressed significantly higher levels of CD11b and CD49d. However, inhibition of L-selectin sheddase activity with KD-IX-73-4 had no effect on the number of neutrophils mobilized in response to rat MIP-2. Blockade of CD18, using a neutralizing monoclonal antibody (mAb), did not inhibit neutrophil mobilization but unexpectedly increased the rate and number of neutrophils released from the bone marrow in response to chemokine, suggesting that CD18 could play a role in neutrophil retention within the bone marrow. Blockade of CD49d using either a selective mAb or a specific antagonist resulted in a dramatic inhibition (> 75%) of the chemokine-stimulated neutrophil mobilization from the bone marrow. These data reveal contrasting roles for CD18 and CD49d in the retention and release of neutrophils from the bone marrow.


Health risk behaviors in adolescents and emerging adults with congenital heart disease: psychometric properties of the Health Behavior Scale-Congenital Heart Disease.
To optimize long-term outcomes, patients with congenital heart disease (CHD) should adopt health-promoting behaviors. Studies on health behavior in afflicted patients are scarce and comparability of study results is limited. To enlarge the body of evidence, we have developed the Health Behavior Scale-Congenital Heart Disease (HBS-CHD). We examined the psychometric properties of the HBS-CHD by providing evidence for (a) the content validity; (b) validity based on the relationships with other variables; (c) reliability in terms of stability; and (d) responsiveness. Ten experts rated the relevance of the HBS-CHD items. The item content validity index (I-CVI) and the averaged scale content validity index (S-CVI/Ave); the modified multi-rater Kappa and proportion of missing values for each question were calculated. Relationships with other variables were evaluated using six hypotheses that were tested in 429 adolescents with CHD. Stability of the instrument was assessed using Heise's method; and responsiveness was tested by calculating the Guyatt's Responsiveness Index (GRI). Overall, 86.3% of the items had a good to excellent content validity; the S-CVI/Ave (0.81) and multi-rater Kappa (0.78) were adequate. The average proportion of missing values was low (1.2%). Because five out of six hypotheses were confirmed, evidence for the validity of the HBS-CHD based on relationships with other variables was provided. The stability of the instrument could not be confirmed based on our data. The GRI showed good to excellent capacity of the HBS-CHD to detect clinical changes in the health behavior over time. We found that the HBS-CHD is a valid and responsive questionnaire to assess health behaviors in patients with CHD.


Nitrite and nitrate levels in cerebrospinal fluid of normal subjects.
In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV) detection. For comparison, the levels of nitrite in the same samples were also measured by reverse phase chromatography coupled with electrochemical detection and those of nitrate by ion chromatography coupled with UV detection. A good correlation was found for the concentration values of both ions obtained with the two procedures. Then, 10.41 +/- 0.47 ng/ml of nitrite and 2.92 +/- 0.37 ng/ml of nitrate could be regarded as reliable values in control subjects. No correlation between age and levels of nitrite and nitrate was observed.


Connective tissue metabolism in muscular dystrophy. Early amino acid changes in collagen types isolated from the gastrocnemius muscle of developing dystrophic chicken embryos.
The amino acid composition of all collagen types present in the gastrocnemius muscle of dystrophic chick embryos showed an altered profile at both day 14 and day 20 in ovo when compared with the controls. The changes observed at both day 14 and day 20 in ovo suggests that there is a removal of polar side-chains in dystrophic collagen and substitution with non-polar amino acids. The amino acid composition data between day 14 and day 20 indicated: (a) a decrease in hydroxylation (hydroxyproline and hydroxylysine) with a concurrent increase in proline and lysine and a decrease in the levels of arginine; (b) the levels of glycine and alanine did not change with age; and (c) the ratios of glycine to hydroxyproline and proline to hydroxyproline changed significantly in all dystrophic collagen types between day 14 and day 20. Contrast analysis results clearly showed that the changes in amino acid composition observed in each dystrophic type of collagen between day 14 and day 20 were not due to the effect of aging but to some other factor(s). This study provides more evidence that a problem lies in the biosynthesis of collagen present in developing muscles of dystrophic chick embryos, particularly with respect to the transcription or translation of procollagen genes and/or a failure in the processing and differentiation of collagen types.


Non-specific vaginitis or vaginitis of undetermined aetiology.
Vaginitis is a complex syndrome that is probably the most common outpatient disease seen by the gynaecologist. The specific aetiologies of vaginitis are many. One of the most common entities, however, is "non-specific vaginitis" which can be subdivided into: Gardnerella vaginitis, anaerobic vaginosis, and vaginitis of undetermined aetiology. The role of Gardnerella as a causative agent for vaginitis has been studied in depth but its specific role remains controversial. Anaerobic vaginosis can be diagnosed by noting on microscopic examination the presence of clue cells, free-floating bacteria and numerous white blood cells (WBC's). Culturing an aliquot of the vaginal discharge reveals a high number of anaerobes. In addition, this condition responds to antibiotics effective against anaerobes, e.g., metronidazole. Vaginitis of undetermined aetiology is more complex and is characterized by a purulent vaginal discharge, a pH of 4.0-4.6, numerous WBC's, and a high concentration of bacteria. The microbiology of this vaginitis includes many facultative Gram-negative rods and Gram-positive cocci. Anaerobes may be present but do not make up a large component of the endogenous microflora. This condition does not respond to the usual antibiotic therapies employed in treating bacterial vaginitis. Since this condition appears to be primarily an inflammatory reaction, it may be responsive to topical antiinflammatory agents such as benzydamine.


Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model.
A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNecALLO) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNecSYN) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.


Reconstitution photoactive yellow protein from apoprotein and p-coumaric acid derivatives.
We report reconstitution of photoactive yellow protein (PYP) from apoPYP and p-coumaric acid derivatives. The addition of p-coumaric acid to the apoPYP sample did not result in the recovery of PYP. In contrast, yellow products were obtained by the addition of p-coumaryl thiophenyl ester or p-coumaric anhydride to the apoPYP sample, the absorption spectra of which were indistinguishable from the spectrum of intact PYP. Our findings provide strong evidence that PYP has the p-coumaryl chromophore. This reconstitution technique opens the way for further biophysical studies of PYP using artificial chromophore analogs.


Utility of peritoneal washing cytology in staging and prognosis of ovarian and fallopian tube neoplasms: a 10-year retrospective analysis.
The prognostic significance of peritoneal washing cytology in gynecologic neoplasms is controversial. The presence of neoplastic cells in peritoneal washings is currently part of the Federation of Gynecology and Obstetrics and American Joint Committee on Cancer TNM staging systems in cases of ovarian and fallopian tube neoplasms without metastasis beyond the pelvis. In this study, we retrospectively reviewed all cases of ovarian and fallopian tube neoplasms in which cytologic studies were performed. The utility of cytology in tumor staging and the relationship between cytology results and patient outcome are studied. All cases of ovarian and fallopian tube neoplasms in our institution between July 2002 and July 2012 were reviewed. Primary tumor characteristics including type and pelvic extension were collected, categorized, and correlated with peritoneal washing cytology. Final tumor staging was reviewed and the impact of positive cytology was evaluated. A total of 120 cases of ovarian and fallopian tube neoplasms without extrapelvic metastasis were identified within the study period. Peritoneal washing cytology was positive in 24% (29/120) of neoplasms and upstaged the tumor 83% (24/29) of the time when positive. Overall, 20% (24/120) of reviewed cases were upstaged based on positive cytology results. Peritoneal washing cytology remains a useful staging tool for ovarian and fallopian tube neoplasms limited to the pelvic cavity. Positive cytology results in upstaging in a significant proportion of the cases regardless of the tumor type. A larger study is needed to analyze follow-up data to determine if upstaging based on positive cytology adversely affects outcome.


Expression of soluble forms of rubella virus glycoproteins in mammalian cells.
Rubella virus (RV) virions contain two envelope glycoproteins, E1 and E2. Removal of hydrophobic regions in their carboxyl termini by genetic engineering caused them to be secreted rather than maintained in cell membranes of transfected COS cells. Truncated E2 was secreted in the absence of E1, whereas E1 lacking its transmembrane domain required coexpression of E2 for export from the cell. Secreted E2 was found to contain both O-linked and N-linked complex glycans, whereas secreted E1 retained virus neutralization and hemagglutination epitopes, suggesting the possibility of using soluble RV antigens as subunit vaccines and for serodiagnostic purposes. Stable Chinese hamster ovary cell lines secreting RV E1 were constructed for large scale preparation of recombinant E1.


The Duke Center for the Study of Aging: one of our earliest roots.
The Duke University Center for the Study of Aging and Human Development (Duke CFA) was established by a multidisciplinary group of visionary scientists in 1955. It is the oldest continually operating center or institute dedicated to aging in the United States. This article outlines the origins of the Duke CFA and summarizes the major research initiatives conducted in its early years. The primary focus is on these landmark studies and their legacies. Those studies made important initial contributions to the knowledge base, introduced measurement tools and research designs that became standards in the field, and served as the impetus for later and current research. The hallmarks of these studies are their multidisciplinary foundations and their focus on the health and well-being of older adults. The Duke CFA's current research clearly builds upon the goals, insights, and empirical results of previous research initiatives. Although aging research is and has been the bedrock of the Duke CFA, developing services responsive to the needs of older adults and multidisciplinary training have also been hallmarks of the Duke CFA. Duke's Geriatric Evaluation and Treatment Clinic was established in 1974 and remains a national model for geriatric assessment. Our postdoctoral research training program has graduated more than 200 scholars and our Geriatric Fellowship program has graduated 113 geriatricians. Many of our graduates have exemplary careers in aging, contributing to important research advances, providing care to thousands of older adults, serving as leaders in the field, and training new generations of gerontologists and geriatricians.


Expression of COX-1, COX-2, and PPAR-gamma in the gastric mucosa of children with Helicobacter pylori infection.
Gastric inflammation in patients with Helicobacter pylori infection is considered to be regulated by many kinds of inflammatory and cytoprotective factors. The present study examined the effects of cyclo-oxygenase (COX)-1, -2, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on gastric mucosal injury in children with H. pylori infection. The subjects were 24 children who underwent endoscopy for the evaluation of anemia or gastrointestinal symptoms, and they were divided into two groups: a H. pylori-positive group and -negative group. The numbers of neutrophils in the gastric mucosa of children with and without H. pylori infection and expression of COX-1, -2, and PPAR-gamma were examined, using reverse transcription-polymerase chain reaction. The numbers of neutrophils were significantly higher in the H. pylori-positive group than in the H. pylori-negative group. The ratio of COX-1 mRNA to COX-2 mRNA in the H. pylori-positive group was significantly lower than that in the H. pylori-negative group. The ratio of PPAR-gamma m-RNA to beta-actin mRNA was significantly higher in the H. pylori-positive group than the H. pylori-negative group. Enhanced production of COX-2 and PPAR-gamma in the gastric mucosa has cytoprotective and anti-inflammatory effects, although the relationship to the carcinogenic activity of COX-2 and PPAR-gamma should be clarified.


An effective method for improving hemostasis in aortic root replacement with a composite graft.
Hemostasis during aortic root replacement with a composite graft, consisting of a separate Dacron graft and a valve, was markedly improved by using a supra-annular aortic wall reinforcing suture (SAWR). Between February 1994 and January 1998, 14 consecutive patients (10 men and 4 women) underwent replacement of the aortic valve and ascending aorta with the SAWR technique. No intraoperative bleeding of the aortic proximal suture line or early death occurred in this group. No patient required reoperation for bleeding of anastomoses. Three of 10 patients who underwent elective operations were operated on successfully without blood transfusion. In addition, no clinical complications related to the SAWR technique were observed in the follow-up period. We conclude that the SAWR technique can be performed easily and may be an effective method for improving proximal hemostasis.


System-level model and experiments for irrigation water alkalinity reduction and enrichment using an atmospheric pressure dielectric barrier discharge.
The treatment of distilled water with varying amounts of dissolved sodium bicarbonate (representing alkalinity) is considered using an atmospheric pressure electrical discharge. The discharge ignited between a capillary tube (used as powered electrode) and a ground electrode wrapped around the beaker holding the treated water consists of streamers propagating in ambient air and striking the water surface. The streamer interaction with water is shown to lead to a decrease in pH and an increase in nitrate concentration. The pH variation with time is shown to be similar to a titration curve for acid-base neutralization with final pH values around 3 for 22 min of treatment. The nitrate ion concentration increase with time is consistent with a two-rate system-level model that is characterized by two asymptotic rates for NO3- creation by the plasma. The two asymptotic rates are calibrated to be about 2.7 μmol/min and 22.5 μmol/min with the transition between the two rates occurring at the breakeven time that is representative of the time required for all dissolved bicarbonate to be consumed by the plasma treatment. The increase in rate of NO3- creation at the breakeven time is attributed to the increase in conductivity of the treated solution once all bicarbonate is consumed thereby modifying the plasma properties. Another system-level model that is based on the observed pH variation is also considered for comparison with measured data. While both system-level models have some discrepancies with the measurements, the two-rate model based on the nitrate ion concentration is concluded to be more useful for determining the NO3- formation rates in the context of irrigation water enrichment. The discrepancies are attributed to the simplicity of the system-level models considered here where the effect of the plasma is completely represented by the creation of just one chemical species in HNO3 thereby neglecting potentially important species such as HNO2 and H2O2. Nevertheless, the proposed system-level model could greatly assist in the design of plasma treatment systems with specified alkalinity, pH and nitrate ion levels for irrigation water.


Selective estrogen receptor modulators and postmenopausal women's health.
Selective estrogen receptor modulators represent an alternative approach to the use of estrogen replacement therapy or hormone replacement therapy for decreasing postmenopausal bone loss, as well as for reducing the incidence of serious cardiovascular disease in this population. Of particular interest is raloxifene, a benzothiophene compound, which binds with high affinity to the estrogen receptor and produces effects similar to estrogen on the skeleton and cardiovascular system but behaves as a complete estrogen antagonist in the uterus and the breast. The pharmacologic profile of raloxifene, a discussion of a possible mechanism of action, and the potential role of this drug in women's postmenopausal health are the subjects of this review.


Motivations for use of opiates among addicts seeking treatment in Shiraz.
This study assessed the characteristics and motivation for substance use among addicts referred to the Shiraz Self-identified Center, an out-patient treatment facility. Data were gathered by a semistructured interview from 306 consecutive addicts seeking treatment and referred from July to September, 1998. Their mean age was 37 yr., and the majority (73.9%) were married. Of these addicts, 28.4% were workers, 13.4% drivers, and 11.4% were unemployed. Modeling or social pressure (43.1%) was identified as the first and enjoyment (fun) was the second most common reason given for opiate use. The majority (97.1%) used opium and 71.9% used alcohol; however, only 2.6% reported current use of alcohol. Other subjects were current users of cigarettes (72.2%), opium (67%), heroin (35%), hashish (2%), hallucinogens (0.3%), and cocaine (0.3%). The most common reason given for currently using opiates was habit (56.5%). About 36% of the subjects reported that they had frequently used opiates for more than a decade. These findings are quite different from those carried out in the West, although there is some overlap. Cultural attitudes toward drug use likely affect the types and amount of use.


[Genetic factors as determinants of drug response].
Pharmacogenetics deals with the influence of genetic factors upon the response to drugs. Therapeutic and side effects are affected by pharmacokinetic and pharmacodynamic changes. Classic examples are presented, in particular those concerning mechanisms of oxidation, acetylation and hydrolysis. The impact of this discipline on therapeutics is discussed.


Unusual electrocardiographic findings associated with type A Wolff-Parkinson-White syndrome.
A 50-year-old woman with Wolff-Parkinson-White (WPW) syndrome presented with unusual electrocardiographic (ECG) findings following the termination of paroxysmal supraventricular tachycardia. The ECG showed three different QRS complexes and irregular R-R intervals. These QRS complexes consisted of: (1) narrow QRS; (2) wide QRS with delta wave; and (3) wide QRS with left bundle branch block (LBBB). The mechanisms of these findings, revealed by electrophysiological study, were: (1) intermittent anterograde left-sided accessory pathway conduction; (2) rate-dependent ipsilateral LBBB; and (3) intermittent retrogradely conducted atrial echoes that occurred due to intraventricular conduction delay resulting from LBBB. Cases of WPW syndrome with these unusual ECG findings, which were clearly interpreted by electrophysiological study, are rare.


Use of generalized linear mixed models to examine the association between air pollution and health outcomes.
Time-series and case-crossover are two techniques that are widely used for assessing the short-term impact of ambient air pollution exposure on health. The generalized linear mixed model (GLMM) methodology is proposed here to study the association between ambient air pollution and health outcomes. Poisson random-effects models are applied to analyze the clustered counts, where the groups of days, determined by the triplet <day of week, month, year>, form the clusters. The proposed technique uses a nested structure for the clusters and allows random-effects for hierarchical factors. A random intercept in the models adjusts for different levels of counts among the clusters. A fixed slope represents a common response to the exposure. The obtained results are consistent with those generated by a classical approach (for example the case-crossover technique). The GLMM technique is a valid alternative methodology for studying air health effects.


Multicenter Study of the Accuracy of the BD MAX™ MDR-TB Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated with Resistance to Rifampin and Isoniazid.
Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB), and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX MDR-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. Outpatient adults with signs and/or symptoms of pulmonary TB were prospectively enrolled. Sputum smear-microscopy and BD MAX were performed on a single raw sputum, which was then processed for mycobacterial culture and phenotypic drug susceptibility testing (DST), BD MAX and Xpert MTB/RIF (Xpert). 1053 participants with presumptive TB were enrolled with median age of 35 (47% female; 32% HIV-infected, and 32% unknown HIV status). In microbiologically-confirmed TB patients, BD MAX sensitivity was 93% (262/282 [95% CI 89, 95]); specificity was 97% (593/610 [96, 98]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175, [98,100]) for smear-positive samples (florescence smear-microscopy), and 81% (87/107, [73,88]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274, [87,94]) for BD MAX and 90% (246/274 [86,93]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared to phenotypic DST was 90% (9/10 [60,98]) and 95% (211/222 [91,97]), respectively. Sensitivity and specificity for detection of INH resistance was 82% (22/27 [63,92]) and 100% (205/205 [98,100]), respectively. The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB, and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally.


Identify measures to diagnose, prevent and treat genital herpes infection during pregnancy and childbirth and neonatal infection. Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines. Genital herpes lesion is most often due to HSV2 (LE2). The risk of HSV seroconversion during pregnancy is 1 to 5% (LE2). Genital herpes ulceration during pregnancy in a woman with history of genital herpes corresponds with a recurrence. In this situation, there is no need for virologic confirmation (grade B). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type specific IgG (Professional consensus). In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) can be administered (grade C). The risk of neonatal herpes is estimated between 25% and 44% in case of initial episode (LE2) and 1% in case of recurrence (LE3) at the time of delivery. Antiviral prophylaxis should be offered for women with first episode genital herpes or recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (grade B). In case of a history of genital herpes without episode of recurrence during pregnancy, it is not recommended routinely offer a prophylactic treatment (professional consensus). A cesarean section should be performed if there is a suspicion of first episode genital herpes at the onset of labor (grade B), in the event of premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and vaginal delivery will be all the more considered in case of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE 3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous acyclovir (60mg/kgs/day 3 times daily) (grade A) prior to the results of HSV PCR (professional consensus). The duration of the treatment depends on the clinical form (professional consensus) CONCLUSION: There is no formal evidence that it is possible to reduce the risk of neonatal herpes in genital herpes during pregnancy. However, appropriate care can reduce the symptoms associated with herpes, the risk of recurrence term and the cesarean rate performed to decrease the risk of neonatal herpes.


Improved grading of bone tumors with the monoclonal antibody Ki-67.
A total of 60 bone tumors and tumor-like lesions presenting various grades of malignancy were investigated immunohistologically with the monoclonal antibody Ki-67 directed against a cell proliferation-associated nuclear antigen. The results obtained agree well with those of flow cytometric and autoradiographic studies on similar tumor entities. The monoclonal antibody Ki-67 was found to be a handy and reliable tool for improved grading of bone tumors.


On the mechanisms of development in monocot and eudicot leaves.
Contents Summary 706 I. Introduction 707 II. Leaf zones in monocot and eudicot leaves 707 III. Monocot and eudicot leaf initiation: differences in degree and timing, but not kind 710 IV. Reticulate and parallel venation: extending the model? 711 V. Flat laminar growth: patterning and coordination of adaxial-abaxial and mediolateral axes 713 VI. Stipules and ligules: ontogeny of primordial elaborations 715 VII. Leaf architecture 716 VIII. Stomatal development: shared and diverged mechanisms for making epidermal pores 717 IX. Conclusion 719 Acknowledgements 720 References 720 SUMMARY: Comparisons of concepts in monocot and eudicot leaf development are presented, with attention to the morphologies and mechanisms separating these angiosperm lineages. Monocot and eudicot leaves are distinguished by the differential elaborations of upper and lower leaf zones, the formation of sheathing/nonsheathing leaf bases and vasculature patterning. We propose that monocot and eudicot leaves undergo expansion of mediolateral domains at different times in ontogeny, directly impacting features such as venation and leaf bases. Furthermore, lineage-specific mechanisms in compound leaf development are discussed. Although models for the homologies of enigmatic tissues, such as ligules and stipules, are proposed, tests of these hypotheses are rare. Likewise, comparisons of stomatal development are limited to Arabidopsis and a few grasses. Future studies may investigate correlations in the ontogenies of parallel venation and linear stomatal files in monocots, and the reticulate patterning of veins and dispersed stoma in eudicots. Although many fundamental mechanisms of leaf development are shared in eudicots and monocots, variations in the timing, degree and duration of these ontogenetic events may contribute to key differences in morphology. We anticipate that the incorporation of an ever-expanding number of sequenced genomes will enrich our understanding of the developmental mechanisms generating eudicot and monocot leaves.


Sedentary Behavior, Physical Activity, and Bone Health in Postmenopausal Women.
The purpose of this study was to determine if bone health at the femoral neck (FN) and lumbar spine (LS) can be predicted from objectively-measured sedentary behavior and physical activity data in postmenopausal women. Waist-mounted ActiGraph GT1M and GT3X devices were used to quantify levels of sedentary and moderate-to-vigorous intensity behavior during a 7-day period in 44 older females. Bone health (normal and osteopenia/osteoporosis) of FN and LS was derived from T scores generated using dual energy x-ray absorptiometry. Binomial logistic regression analysis indicated that sedentary time and number of breaks in sedentary behavior were significant predictors of osteopenia/osteoporosis at the FN, but not at the LS. Adherence to physical activity guidelines was not a significant predictor of bone health at the FN or LS. Our findings suggest that more frequent interruptions in sedentary behavior are associated with improved bone health in postmenopausal women.


Pulmonary disease in children with AIDS.
Children with acquired immunodeficiency syndrome (AIDS) may present with recurrent pneumonias or chronic debilitating illness. The chest radiographs of these patients demonstrate homogeneous densities representing staphylococcal or other pyogenic infections. Pneumocystis carinii pneumonia produces a diffuse, symmetric, fine-to-medium, reticulonodular pattern. Lymphocytic interstitial pneumonitis, a disease that is now an index diagnosis of AIDS in children under 13, may appear as a chronic, diffuse, small nodular infiltrate. An increasing number of pediatric AIDS patients will be observed in the future because of the large number of human immunodeficiency virus-infected women who are of childbearing age.


300% Enhancement of Carrier Mobility in Uniaxial-Oriented Perovskite Films Formed by Topotactic-Oriented Attachment.
Organic-inorganic perovskites with intriguing optical and electrical properties have attracted significant research interests due to their excellent performance in optoelectronic devices. Recent efforts on preparing uniform and large-grain polycrystalline perovskite films have led to enhanced carrier lifetime up to several microseconds. However, the mobility and trap densities of polycrystalline perovskite films are still significantly behind their single-crystal counterparts. Here, a facile topotactic-oriented attachment (TOA) process to grow highly oriented perovskite films, featuring strong uniaxial-crystallographic texture, micrometer-grain morphology, high crystallinity, low trap density (≈4 × 1014 cm-3 ), and unprecedented 9 GHz charge-carrier mobility (71 cm2 V-1 s-1 ), is demonstrated. TOA-perovskite-based n-i-p planar solar cells show minimal discrepancies between stabilized efficiency (19.0%) and reverse-scan efficiency (19.7%). The TOA process is also applicable for growing other state-of-the-art perovskite alloys, including triple-cation and mixed-halide perovskites.


Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques.
To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.


The embryogenesis of congenital vertebral dislocation: early embryonic buckling?
Congenital vertebral dislocation (CVD) is a rare congenital spinal malformation characterized by a translatory or rotatory vertebral displacement, or both, at a single level, that results in an abrupt angulation of the neural canal. The more caudal vertebra is dysplastic and appears at first glance to be posteriorly dislocated into the vertebral canal as a posterior hemivertebra, but is actually well aligned with the more caudal vertebral column. Unfortunately, the present classification of complex congenital vertebral anomalies is confusing, and CVD has been grouped together with other congenital vertebral malformations under the terms 'segmental spinal dysgenesis', 'medial spinal aplasia', and others. Moreover, a putative embryonic mechanism has never been proposed for CVD. Based upon our experience with 6 children and a critical review of the literature, we identify CVD as a distinct entity having characteristic anatomical features. We propose a novel putative embryonic mechanism - early embryonic 'buckling' - which likely occurs by the 6th embryonic week, prior to the period of axonal outgrowth and the beginning of vertebral chondrification.


[Pregnancy following in vitro fertilization and intratubal embryo transfer].
The intratubar embryotransfer is a variation of the in vitro fertilization, where the procreated preimplantation-embryos are not transferred into the cavum uteri but the tube(s). The intracavitar embryotransfer is the only possibility to treat irreparable tubar sterility in contrary to sterility not caused by the tubes where the transfer can be effected directly into the tubes. Considering the gamete intrafallopian transfer (GIFT) one can assume, that the tubes are the best physiological place for the very young embryo's evolution. In opposition to the GIFT-method the embryotransfer into the tubes will be done only if a fertilization was proved: thereby superfluous operations can be avoided and additional diagnostic hints can be gained. The valuable indications are the following ones: idiopathic sterility, certain cases of andrological subfertility and immunological sterility; probably for some kinds of the last indication from the intratubar embryotransfer there will result a special area of application. It is reported about a viable pregnancy after in vitro fertilization and intratubar embryotransfer. The new method is supposed to be called IVF/IT-ET (i.e. in vitro fertilization and intratubar embryotransfer).


Structure, function, control: a system-constructive approach.
A general biological concept of the unity of structure and function in biological systems at all levels of their organization-cell, tissue, organ and organism-is well known. However, the constructive contents of such unity remain unclear. It appears that until we learn to separate and allocate structural and functional problems of biological systems construction, we cannot understand how this unity is reached. Or else, there is a methodological problem: how to separate and to allocate the basic categories of biological self-organization? Here, we consider different biological tissues in order to separate, in the first place, the basic concepts-structure, function, control-as independent systems which have their own referents. Then to solve the problem of association, a concept of "equipment" is introduced: the structure is equipped with function, the function is equipped with control. As a result, any elementary cycle of bioorganization is represented as a sequence of phases: (1) formation of structural basis, (2) functional equipment of structure, (3) libernetical equipment of function-differentiation of variability freedoms, (4) establishment of control to overcome the superfluous freedom of structural and functional organization.


Extending Phenomenological Crystal-Field Methods to C_{1} Point-Group Symmetry: Characterization of the Optically Excited Hyperfine Structure of ^{167}Er^{3+}:Y_{2}SiO_{5}.
We show that crystal-field calculations for C_{1} point-group symmetry are possible, and that such calculations can be performed with sufficient accuracy to have substantial utility for rare-earth based quantum information applications. In particular, we perform crystal-field fitting for a C_{1}-symmetry site in ^{167}Er^{3+}:Y_{2}SiO_{5}. The calculation simultaneously includes site-selective spectroscopic data up to 20 000 cm^{-1}, rotational Zeeman data, and ground- and excited-state hyperfine structure determined from high-resolution Raman-heterodyne spectroscopy on the 1.5 μm telecom transition. We achieve an agreement of better than 50 MHz for assigned hyperfine transitions. The success of this analysis opens the possibility of systematically evaluating the coherence properties, as well as transition energies and intensities, of any rare-earth ion doped into Y_{2}SiO_{5}.


Experience with transumbilical breast augmentation.
Transumbilical breast augmentation (TUBA), an endoscopicassisted procedure in which saline breast prostheses are inserted through the umbilicus, is a patient-driven, frequently performed procedure that remains controversial. The author describes the operative technique and results in 90 patients who underwent TUBA between October 1996 and July 2000 by the same surgeon in a community practice. A total of 85 patients underwent submammary TUBA and 5 patients underwent submuscular TUBA. Seventy patients were available for follow-up. Postoperative results of the 70 patients were graded as very good in 56 (80%), good in 12 (17%), and fair in 2 (2.9%). Complications were conversion to an open approach in 1 patient and an accidental submuscular entry into the pocket in 1 patient. There were four capsular contractures (5.7%), 5 patients (7.1%) were reoperated: 2 for capsulectomies, 1 for implant buckling, 1 for scar revision, and 1 for removal of the implants. There were no implant ruptures, hematomas, or infections. Advantages of TUBA include minimal scarring, remote incision, short operating time, low capsular contracture rate, and rapid recovery. These results of this evolving procedure suggest that in select patients TUBA provides a high level of patient satisfaction and low complication rates. As TUBA techniques for submuscular placement continue to develop, more patients may become TUBA candidates.


1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists.
Bisarylmethoxyethers have been identified with nanomolar 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 1, 2, 8, 12, 14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their therapeutic potential is currently under further investigation.


Cytochemical localization of hydrogen peroxide production in the rat uterus.
A reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H)-dependent H2O2-generating activity of the rat uterus was investigated both electron cytochemically and biochemically. We tried to cytochemically demonstrate H2O2 generation from the oxidation of reduced NADH or NADPH using the cerium method. NADPH oxidation resulted in electron-dense deposits on the apical plasma membrane covering the microvilli of the surface epithelium of the lightly fixed endometrium. In control specimens incubated in a medium from which substrate was omitted, no such deposits were observed. The reduction of ferricytochrome c due to NADH oxidation was spectrophotometrically detected in the lightly fixed uterus. Absorption at 550 nm increased with the addition of NADH, but not with that of NAD. The reaction was weakened by preheating and adversely affected by the addition of superoxide dismutase, but it was not inhibited by adding 50 mM sodium azide. These results suggest that a kind of NAD(P)H oxidase, generating H2O2 via superoxide formation, may possibly be present on the apical plasma membrane of the rat endometrial epithelium.


The electrophysiological effects of a brain injury on auditory memory functioning. The QEEG correlates of impaired memory.
The effect of a brain injury on the quantitative EEG (QEEG) variables during an auditory memory activation condition was examined with 56 normal subjects and 85 mild traumatic brain-injured (MTBI) subjects. An analysis was conducted on the different response patterns of the two groups, the variables which were correlated with memory performance in the brain-injured group, and the variables which predicted the memory score for the combined two groups (normal and brain injured). The three conditions included the input task, the immediate recall, and the delayed recall task. The consistent effect of a brain injury was a lowering of the connectivity patterns in the beta1 and beta2 frequencies (phase and coherences) and increases predominantly in the relative power of beta1 (13-32Hz), which were correlated with the differences in recall. There is a subtle shift to right hemisphere/right temporal functioning and employment of the higher beta1 and beta2 frequencies (phase and coherence) in the response pattern of the MTBI subject. Memory functioning is predominantly positively correlated with connection activity (phase and coherence) and negatively correlated with beta activation at specific locations.


[Patellectomy: results of a long-term follow-up].
The authors are in disagreement with the literature on the results of patellectomy after comminuted fracture of the patella. They assessed retrospectively 17 patients who underwent unilateral total patellectomy between 1955 and 1980. Subjective and objective (clinical examination, radiologic examination and Cibex II studies) assessment was carried out for each patient using the contralateral healthy knee as a control. The results demonstrated 88% patient satisfaction, no ligamentous instability and no early arthrosis but a decrease in extensor muscle strength to 75% of normal. The authors conclude that total patellectomy is better tolerated and causes less morbidity than suggested in the literature.


Fracture of a ceramic liner in a total hip arthroplasty with a sandwich cup.
Alumina ceramic-on-ceramic total hip arthroplasty (THA) has been widely used due to its advantages such as low wear, scratch resistance, wettable surface and relatively low biological reactivity of the wear particles. Nevertheless, this material in THA still persists to be one of the major concerns about the risk of fracture, due to its brittleness. Many authors have reported a fracture of the ceramic head but few reported a fracture of the ceramic acetabular insert. In order to reduce the rigidity of the ceramic-on-ceramic coupling and prevent an impingement between the rim of the ceramic liner and the metal neck of the femoral stem, a modular acetabular component with a sandwich insertion (alumina/polyethylene/titanium) was proposed. We report the fracture of the ceramic acetabular liner of such a ceramic sandwich cup due to a slightly retroverted position of the cup that causes an impingement between the femoral stem and the rim of the insert. The fracture occurred 3 years after the operation without trauma. At revision the entire cup was replaced using a polyethylene liner without inner ceramic liner.


Is Shared Decision Making a Utopian Dream or an Achievable Goal?
The idea of shared decision making (SDM) between patient and physician grew out of a generalized challenge to traditional social hierarchies that occurred in the middle of the last century. Governments have espoused SDM, thousands of articles about it have been published, and evidence has shown that it improves some of the healthcare processes as well as patient outcomes. Yet it has not been widely adopted. From their cross-disciplinary perspective (practical theology and clinical medicine), the authors locate this reluctance in the unfolding of scientific paradigm shifts, summarize the perceived risks and benefits of SDM and the evidence for each, and suggest practical, achievable approaches for clinicians. Finally, they explore some important emerging territories for SDM.


Distant metastases in nasopharyngeal carcinoma.
Three hundred and fifty-two consecutive cases of nasopharyngeal carcinoma were analysed to determine the pattern of distant metastases. Diagnosis of distant metastases was made wholly on clinical signs and radiography. Ninety-nine patients developed distant metastases, an incidence rate of 28.1%. There did not appear to be any difference in "risk" by age or sex. The predilection of this cancer to develop skeletal metastases is further confirmed. Pulmonary and hepatic involvement were the next commonest. Both extent of primary tumour (T) and cervical lymph node status (N) exerted a significant influence on the probability of metastases developing. Thus significant differences in metastatic rate were observed between T0/T1, T2 and T3/T4 and N0, N1, N2 and N3 groups. 65.6% of metastatic cases had control of local disease (nasopharynx and cervical lymph nodes). When metastases are diagnosed the prognosis is gloomy with a median survival under four months and a fatality rate of 91% within a year of first metastasis.


Nipple attachment and survival in neonatal olfactory bulbectomized rats.
Seven-day-old rat pups were olfactory bulbectomized, cortical lesioned, or sham lesioned, tested for nipple attachment 24 hr after surgery, then housed with their dam and weighed daily for the next 7 days. On the basis of histological findings the bulbectomized animals were divided into two subgroups: Those with removal of all olfactory bulb tissue (n = 9) and those in which some cellular elements remained in the lesioned area (n = 7). There were no differences between sham and cortical lesioned groups for nipple attachment behavior or weight gain. The completely bulbectomized pups did not show nipple attachment, lost weight each day, became moribund and had to be sacrificed by the fifth postoperative day. Deficits in incompletely bulbectomized pups were somewhat less severe and each of these survived and maintained or gained weight in the latter part of the test period. These results suggest that suckling may be critically dependent upon olfaction in 8 day or older pups and that significant savings in this behavior may be mediated by small remnants of olfactory bulb tissue.


Risk factors for meconium aspiration in meconium stained amniotic fluid.
Meconium aspiration syndrome (MAS) is a life-threatening respiratory disease in infants born through meconium stained amniotic fluid (MSAF). The purpose of this study was to determine risk factors for MAS in the newborns of mothers who had meconium stained amniotic fluid in labour. A retrospective study of all full-term pregnancies with MSAF from May 2003 to October 2004 was designed at a teaching hospital. Development of MAS was the primary outcome. Maternal details, mode of delivery and neonatal details (Apgar score, reassuring or non-reassuring fetal heart rate tracing and birth weight) were evaluated. During the study period, there were 2,603 deliveries of whom 302 (11.6%) had MSAF. MAS developed in 64 of these infants (21.1%). Compared with healthy neonates with MSAF, those with MAS had higher rate of non-reassuring fetal heart rate (FHR) tracing, thick meconium and Apgar score < or =5 at 5 min. The neonatal birth weight was lower in the MAS group, maternal age, parity, gestational age and mode of delivery were not significantly different in the two group. We found the severity of meconium, low Apgar score at 5 min and non-reassuring FHR tracing was associated with MAS in MSAF pregnancies.


Early withdrawal of calcineurin inhibitor from a sirolimus-based immunosuppression stabilizes fibrosis and the transforming growth factor-β signalling pathway in kidney transplant.
The focus in renal transplantation is to increase long-term allograft survival. One of the limiting factors is calcineurin inhibitor (CNI)-induced fibrosis. This study attempted to examine the histological aspect of interstitial fibrosis and the modulation of the transforming growth factor-β (TGF-β) canonical signalling pathway following early withdrawal of CNI from sirolimus-based immunosuppressive therapy. Forty-five kidney transplant recipients with low-medium immunologic risk were randomized and underwent protocol biopsies obtained at the time of transplantation and at 3 and 12 months thereafter. The recipients were taking tacrolimus, sirolimus and prednisone. After the 3rd month, patients were randomized into two groups: sirolimus (SRL) (removed CNI and increased sirolimus) and tacrolimus (TAC) (maintained CNI). Renal biopsies were analyzed according to Banff's 2007 criteria. The sum of Banff's ct and ci constituted the chronicity index. Fibrosis was evaluated by the histomorphometrical analysis of the total collagen and myofibroblast deposition. Immunohistochemical characterization and quantification of TGF-β, TGF-β receptor 1 (TGF-β-R1), receptor 2 (TGF-β-R2) and phospho-Smad2/3 (p-Smad2/3) were performed. Maintenance of CNI was associated with the increase of the surface density of collagen and α-smooth muscle actin (α-SMA), (P = 0.001). Furthermore, increased TGF-β (P = 0.02), TGF-β-R1 (P = 0.02), p-Smad2/3 (P = 0.03) and stabilized TGF-β-R2. On the other hand, the removal of CNI with increase in the dose of sirolimus limited the enhancement of the chronicity index at 12 m (SRL, 2.18 vs TAC, 3.12, P = 0.0007), diminished the deposition of fibrosis and promoted the stabilization of TGF-β, TGF-β-R2, p-Smad2/3 and myofibroblasts as well as the reduction of TGF-β-R1 (P = 0.01). The early withdrawal of CNI limited the fibrosis progression through the stabilization of chronicity index and of the canonical TGF-β signalling pathway.


CeasIng Cpap At standarD criteriA (CICADA): Implementation improves neonatal outcomes.
A previous randomised controlled trial (RCT) in babies born < 30 weeks gestation found the so-called CICADA method (ceasing continuous positive airways pressure (CPAP) with a view to remain off rather than slow weaning) significantly reduced CPAP time. Post-RCT we introduced the CICADA method and evaluated whether the improved outcomes of the CICADA method during the RCT were replicated in clinical practice. The aim of the study is to compare cardio-respiratory outcomes in PBs < 30 weeks GA over three epochs: (i) pre RCT, (ii) during RCT and (iii) post RCT implementation. The study used prospective data to compare baseline characteristics and cardio-respiratory outcomes over the three epochs. There were 270/393(69%) PBs < 30 weeks GA who fulfilled the inclusion criteria over the three epochs. No significant differences were found in GA or birthweight between the three epochs (27.9 ± 1.3, 27.7 ± 1.4, 28.0 ± 1.3 (weeks ± 1 standard deviation); and 1100 ± 252, 1086 ± 251, 1094 ± 320 (grams ± 1 standard deviation)). There were significant decreases in CPAP days and corrected GA to cease CPAP post implementation (20.5 ± 2.1, 21.1 ± 2.1, 16.5 ± 1.8 (days ± SE); P = 0.006 and 33.3 ± 0.4, 33.5 ± 0.4, 32.6 ± 0.4 (weeks ± SE); P = 0.01). Compared with the pre RCT epoch, there were significant reductions in patent ductus arteriosus (36/78 (46%), 33/87 (37%), 18/103 (17%); P < 0.001) and chronic lung disease (40/78 (51%), 19/87 (21%), 30/103 (29%); P < 0.001). CPAP time, corrected GA to cease CPAP, patent ductus arteriosus and chronic lung disease significantly reduced following the introduction of the CICADA method. Early cessation of CPAP expedites the transition from neonatal intensive care to special care.


Surface Characteristics Control the Attachment and Functionality of (Chimeric) Avidin.
The physical adsorption (physisorption) of proteins to surfaces is an important but incompletely understood factor in many biological processes and is of increasing significance in bionanotechnology as well. Avidin is an important protein because of strong avidin-biotin binding, which has been exploited in numerous applications. We have undertaken thorough experimentation on the physisorption of avidin, to chemically different flat surfaces of Si and graphite and also to the curved version of the latter, on multiwalled carbon nanotubes (MWNTs) of different diameters. The difference in the behavior of avidin on Si versus graphite is drastic; on Si, avidin deposits as single globular tetrameric units and maintains functionality, whereas on graphite, it forms irregular networks of two-layer thick filaments, where the first layer has lost its biological activity. On MWNTs, avidin also deposits as one-dimensional formations, or stripes, but these appear to order in a perpendicular arrangement to the MWNT axis. A better understanding of protein-surface interactions is essential for the development of robust and reliable methods for biofunctionalization of materials. This work also provides insights into the importance of the nanoscale surface architecture.


Self-assembly of coordination polymers into multi-stranded nanofibers with tunable chirality.
We have demonstrated that the formation of multi-stranded nanofibers with tunable chirality from coordination polymers and their hierarchical assembly into interconnected 3-D networks leading to thermoresponsive gelation.


Measuring occupational balance and its relationship to perceived stress and health: Mesurer l'équilibre occupationnel et sa relation avec le stress perçus et la santé.
There is an assumption that occupational balance is integrally related to health and well-being. This study aimed to investigate test-retest reliability of the English-translated Occupational Balance Questionnaire (OBQ), its relationship to measures of health (Short Form Health Survey-36 Version 2.0 [SF-36v2]) and stress (Perceived Stress Scale-10; PSS-10), and demographic differences in OBQ scores in Canadian adults. Test-retest reliability (2 weeks) was assessed using intraclass correlation (ICC) coefficients. Online surveys from 86 adults were analyzed using descriptive, correlational, and t test statistics. OBQ test-retest reliability was ICC = 0.74 (95% CI [0.34, 0.90]; p = .003) when excluding an influential case ( n = 20). OBQ correlations with PSS-10 were r = -.72; with SF-36v2 Mental Component Score, r = .65; and with Physical Component Score, r = .31; all p < .001. Age and gender had no impact on OBQ scores. Findings help elucidate relationships among health, stress, and occupational balance; however, further psychometric testing is warranted before using OBQ for clinical purposes.


Quality, functional and sensory evaluation of pasta fortified with extracts from Opuntia ficus-indica cladodes.
The stems of Opuntia ficus-indica, known as cladodes, are a rich source of soluble fibers, which makes them an important candidate for the production of functional foods. Tagliatelle of durum wheat fortified with Opuntia cladode extract (OCE) at different levels of addition (10-30%, v/w) was prepared on a laboratory scale and quality characteristics and sensory acceptability were assessed. The main quality parameters (optimal cooking time, swelling index, cooking loss, dry matter) and sensory analysis on a nine-point hedonic scale were comparable with those of the control pasta sample (no added OCE) when durum wheat was supplemented with OCE at up to 20% (v/w). An in vitro human simulated gastrointestinal digestion in the presence of cholesterol or its main dietary oxidized derivative, 7-ketocholesterol, showed that OCE-fortified pasta strongly reduced the bioaccessibility of both the sterols (the higher the incorporated OCE level, the higher the effect). Moreover the extent of starch digestion decreased with increasing levels of OCE. The results of the present study indicate that OCE-fortified pasta comprises a food with healthy properties, such as blood cholesterol- and glucose-lowering capabilities. © 2019 Society of Chemical Industry.


[An analysis of the mortality of patients with suppurative-inflammatory diseases of the maxillofacial area].
The frequency of acute purulent inflammatory diseases of maxillofacial area and their complications (thrombosis of the cavernous sinus, abscess of the brain, sepsis) were investigated. These complications are responsible for 0.56% of lethal outcomes. Early diagnosis and intensive treatment of such conditions are a must.


Pd(II)-catalyzed oxidative alkoxycarbonylation of 2-phenoxypyridine derivatives with CO and alcohols.
A Pd(ii)-catalyzed oxidative alkoxycarbonylation of phenol derivatives with atmospheric pressure of CO-O2 and alcohols has been achieved. The reaction provides an efficient strategy for the synthesis of carboxylic esters and can be applied to the late-stage modification of complex molecules.


[Cytopenias following kidney transplantation].
Cytopenias frequently occur during the first months after solid organ transplantation. Many mechanisms are involved but drugs toxicity and infections are the major causes of cytopenias. Anemia is also related with chronic kidney graft dysfunction. Several drugs are pointed out but antithymocyte globulin, antiproliferative drugs and antiviral drugs are mainly responsible for cytopenias. Infectious causes are mainly viral and can rarely induce macrophage activation syndromes. Passenger lymphocyte syndrome is only described after ABO incompatible transplantations. Thrombotic microangiopathies are frequent and multifactorial (antibody mediated rejection, calcineurine inhibitors toxicity, infections, initial nephropathy recurrence). Cytopenias following transplantation increase the risk of infectious disease by neutropenia and generally lead to an immunosuppressive therapy reduction. It seems to increase the risk of rejection when the baseline immunosuppressive level is not further restored.


Psychophysiological correlates of social skills deficits in persons with schizophrenia.
Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.


Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls.
Randall's plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs (n = 64) and nonstone formers (n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls (P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.


Antioxidative or prooxidative effect of 4-hydroxyquinoline derivatives on free-radical-initiated hemolysis of erythrocytes is due to its distributive status.
7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not very satisfactory. This fact motivates us to study the relationship between the structure of 4-hydroxyquinoline with various substituent and its antioxidant effect against free-radical-initiated peroxidation: the hemolysis of human erythrocyte initiated thermally by water-soluble initiator, 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4-hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4-hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3-carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7-chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied and found that all these chemicals dissolved in dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To clarify the relationship between the distributive status of the chemicals and their antioxidant effect, the chemical has been dissolved in the vesicle of dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants either used alone or used in combination with alpha-tocopherol (TOH), demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they are packaged in the DPPC vesicle. This can be understood that the electron-attracting group, i.e. -COOC(2)H(5), -COOH, at the ortho position to the hydroxy group of quinoline makes the phenoxy radical of quinoline derivatives active by attracting negative charge from the electron-deficient radical site. These unstable free radicals preserved in DPPC vesicle can initiate additional propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without electron-attracting group are antioxidants even in DPPC vesicle either used alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much better than CQ either used alone or in combination with TOH, indicating that FQ has the potential to replace CQ to be an antioxidant drug. Therefore, the antioxidant/prooxidant effect is not only correlated with the molecular structure but also the distributive status in the reaction system.


Ouabain Modulates the Distribution of Connexin 43 in Epithelial Cells.
The fact that ouabain has been identified as an endogenous substance, led us to inquire its physiological role in epithelial cells. Based on previous observations, we hypothesized that it influences processes related to cell contacts. Previously we have shown that nanomolar concentrations of ouabain up-regulate tight junctions, accelerate ciliogenesis, and increase gap junctional intercellular communication (GJIC). Given that silencing assays indicated that connexin 43 (Cnx43) is involved in the GJIC response, in the present work we study whether ouabain affects Cnx43 expression and distribution. We seeded confluent monolayers of epithelial renal MDCK cells and incubated them with 10 nM ouabain during 1 h. Then we measured, by densitometric analysis of Western blot assays, the amount of Cnx43 in cells and in fractions enriched of plasma membrane. We also studied its localization with immunofluorescence and confocal microscopy. Cnx43 is remarkably displayed, outlining the borders of cells gathered in clusters, randomly scattered throughout the monolayer. Ouabain increases the density of such clusters, as well as the average number of cells per cluster, without inducing the synthesis of new Cnx43. It also promotes relocation towards the membrane, of subunits already available. The fact that such changes are inhibited by PP2 and PD98059 indicates that a signaling pathway, that includes c-Src and ERK1/2, is involved in this response. Ouabain induces the translocation of Cnx43 from the cytoplasm to the plasma membrane. These findings support our hypothesis that one of the physiological roles of ouabain is the modulation of physiological processes that depend on cell to cell contacts.


Video-imaging of lumen narrowing; muscle shortening and flow responsiveness in isolated bronchial segments of the pig.
The amount of smooth muscle shortening required to cause narrowing of the bronchial lumen and to significantly alter airflow in an airway has not not been measured. Accordingly, in this study, the lumens of isolated fluid-filled bronchial segments from pigs were directly visualized using a fibreoptic endoscope and video-recording. The extent of lumen narrowing was related to smooth muscle contraction, determined morphometrically, and to bronchial lumen flow. Narrowing was produced by electrical field stimulation (EFS), (70 V, 20 Hz, 2-3 ms) and acetylcholine (ACh), (10(-5)-10(-2) M). The diameter of the relaxed bronchial lumen and the reduction in diameter produced by maximum electrical field stimulation were both greater when the transmural pressure was increased (from -8 to 20 cmH2O). The percentage change in diameter produced by electrical field stimulation was not, however, significantly different over this pressure range. Electrical field stimulation caused the bronchial lumen to narrow by 28.5 +/- 3.3% in diameter, and by 45.7 +/- 3.8% in cross-sectional area, at zero transmural pressure. Maximum doses of acetylcholine (10(-2) M) reduced the lumen diameter by 48.3 +/- 3.3%, and the area by 70.3 +/- 4.8%. In separate experiments, maximum doses of ACh stopped the flow of Krebs solution perfused through the lumen of bronchial segments. Morphometric measurements indicated that smooth muscle shortened by a maximum of 32.5 +/- 2.8% to acetylcholine 10(2) M, relative to fully-relaxed dimensions. Simultaneous imaging of the lumen and adventitia of bronchi showed that the luminal margin narrowed more than the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)


The Dunedin Multidisciplinary Health and Development Study: a 15 year longitudinal study.
This article describes the Dunedin Multidisciplinary Health and Development Study, a longitudinal study of 1037 children studied at birth and followed-up at age 3, with the majority being followed up every 2 years thereafter, to age 15. The paper includes a description of the setting for the study, the historical background, establishment of the study, the sample, follow-up rates, changes in sample characteristics over time, the procedures, the data gathered at each phase and the investigators responsible. Some of the topics studied over the years are set out in a table of descriptors which includes references to refereed journal articles that include results relating to the topics. Plans for the future are also described. Reflections on some of the reasons why the study has been successful are noted. The article concludes with a full list of publications and reports (1-328), current as at 1 July 1989.


Antioxidants in bakery products: a review.
Fats impart taste and texture to the product but it is susceptible to oxidation leading to the development of rancidity and off-flavor. Since ancient times it has been in practice to use antioxidants in foods. Discovery of synthetic antioxidants has revolutionized the use of antioxidants in food. The effect of these antioxidants in bakery products were reviewed and found to be effective in enhancing the shelf life. Animal experimental studies have shown that some of the synthetic antioxidants had toxigenic, mutagenic, and carcinogenic effects. Hence there is an increasing demand for the use of natural antioxidants in foods, especially in bakery products. Some of the natural antioxidants such as alpha-tocopherol, beta-carotene, and ascorbic acid were already used in bakery products. These natural antioxidants are found to be effective in enhancing the shelf life of bakery products but not to the extent of synthetic antioxidants. Baking processing steps may lower the antioxidative activity but techniques such as encapsulation of antioxidants can retain their activity. Antioxidative activity of the plant extracts such as garcinia, curcumin, vanillins, and mint were reviewed but studies on their role in bakery products were limited or very few. Hence there is a wide scope for study under this direction in depth.


mTOR inhibitors in pediatric kidney transplantation.
The mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly being used in pediatric kidney transplantation in different combinations and doses. Several studies have shown beneficial effects of using mTOR inhibitors in children after pediatric renal transplantation. A switch to a low-dose calcineurin inhibitor (CNI) and mTOR inhibitor has been proven to stabilize the glomerular filtration rate. Additionally, de novo studies using a low-dose CNI and an mTOR inhibitor have shown good graft survival and a low number of rejections. Side effects of mTOR inhibitors, such as hyperlipidemia, wound healing problems, and proteinuria, mainly occur if high doses are given and if treatment is not combined with a CNI. Lower doses of mTOR inhibitors do not result in growth impairment or reduced testosterone levels. Treatment with mTOR inhibitors is also associated with a lower number of viral infections, especially cytomegalovirus. Due to their antiproliferative effect, mTOR inhibitors could theoretically reduce the risk of post-transplant lymphoproliferative disease. mTOR inhibitors, especially in combination with low-dose CNIs, can safely be used in children after kidney transplantation as de novo therapy or for conversion from CNI- and mycophenolate mofetil-based regimens.


Toxic Chemical from Plastics Attenuates Phenylbiguanide-induced Cardio-respiratory Reflexes in Anaesthetized Rats.
Bisphenol A (BPA) attenuated phenylbiguanide (PBG)-induced cardio-respiratory reflexes involving decreased vagal afferent activity. BPA leaches out from plastics thus it is expected that chronic exposure to plastic boiled (PBW) water will also produce similar changes. Therefore, the present study was undertaken to evaluate the effects of chronic ingestion of PBW on PBG evoked reflexes and were compared with BPA. Adult female rats were ingested BPA containing pellets (2 µg/kg body weight)/PBW/tap water (ad libitum) for 30 days. On day 30, the animals were anaesthetized and BP, ECG and respiratory excursions were recorded. Further, PBG was injected intravenously to evoke cardio-respiratory reflexes and at the end lungs were excised for histopathological examination. BPA concentration in PBW was 6.6 µg/ml estimated by HPLC. In rats receiving tap water, PBG produced bradycardia, hypotension and tachypnoea. In PBW/BPA treated groups, PBG-induced reflexes were attenuated significantly along with emphysematous and consolidative changes in lungs. The present results indicate that PBW attenuates the protective cardio-respiratory reflexes and also produces histopathological changes in lungs.


[Effect of arteparon on the formation of calcium phosphate and calcium pyrophosphate crystals--comparative experimental study].
The influence of Arteparon on crystal formation in vitro has been examined in calcium orthophosphate and in calcium pyrophosphate mixtures. Similar factors may be operative in the cartilage calcification processes, and thus in chondrocalcinosis. Authors have ascertained that Arteparon - like chondroitin sulphate - inhibits crystal separation. The optimal concentration for this inhibition lies in the range of the proteoglycan content of normal cartilage. Where there are physiological phosphate-pyrophosphate ratios and a low magnesium concentration, it is certain that Arteparon has an inhibiting effect. Apart from the spatial structure of the substance, the importance of negative charge density for the inhibition of separation of calcium phosphate and pyrophosphate crystals is thought to contribute to this effect of Arteparon.


Impact of freeze drying on drug resistance pattern of few Escherichia coli strains.
Drug resistant strains of E. coli were freeze dried for long term preservation. Certain drug resistance markers were maintained after freeze drying while others were not. Streptomycin and sulphonamide resistance markers resisted freeze drying. Ampicillin, cephelaxin and neomycin resistances developed very frequently and except gentamicin all the markers were lost in varying percentage after freeze drying.


An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease.
Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens. The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia. ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis. ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.


Sensitivity assessment of sea lice to chemotherapeutants: Current bioassays and best practices.
Traditional bioassays are still necessary to test sensitivity of sea lice species to chemotherapeutants, but the methodology applied by the different scientists has varied over time in respect to that proposed in "Sea lice resistance to chemotherapeutants: A handbook in resistance management" (2006). These divergences motivated the organization of a workshop during the Sea Lice 2016 conference "Standardization of traditional bioassay process by sharing best practices." There was an agreement by the attendants to update the handbook. The objective of this article is to provide a baseline analysis of the methodology for traditional bioassays and to identify procedures that need to be addressed to standardize the protocol. The methodology was divided into the following steps: bioassay design; material and equipment; sea lice collection, transportation and laboratory reception; preparation of dilution; parasite exposure; response evaluation; data analysis; and reporting. Information from the presentations of the workshop, and also from other studies, allowed for the identification of procedures inside a given step that need to be standardized as they were reported to be performed differently by the different working groups. Bioassay design and response evaluation were the targeted steps where more procedures need to be analysed and agreed upon.


Two new species of Eimeria from peacocks (Pavo cristatus) in Saudi Arabia.
Fifteen fecal samples from peacocks (Pavo cristatus) in Saudi Arabia contained oocysts of Eimeria riyadhae n. sp. in two peacocks and oocysts of E. arabica n. sp. in one peacock. Sporulated oocysts of Eimeria riyadhae are ellipsoidal, 27-30.5 x 20.5-25 (28.8 +/- 1.3 x 22.4 +/- 1.6) micron, with a two-layered wall and bilobed polar body, but without a micropyle or residuum. The sporocysts are ovoid, 11-14.5 x 6.5-8 (13.2 +/- 1.2 x 7.2 +/- 0.6) micron with a thick, knob-like Stieda body and a residuum. Sporulated oocysts of Eimeria arabica are spheroidal, 17.5-21.5 x 17.5-21.5 (19.2 +/- 1.6 x 19.2 +/- 1.6) micron, with a two-layered wall and two refractile polar bodies, but without a micropyle or residuum. The sporocyts are elongate ovoid, 9.5-12 x 4-6.5 (11.2 +/- 0.9 x 5.5 +/- 0.88), with a small crescent-shaped Stieda body. The host bird belongs to the order Galliformis.


Retrobulbar hemorrhage occurring after placement of a superior rectus muscle suture.
A retrobulbar hemorrhage occurred in a 25-year-old woman after placement of a superior rectus muscle traction suture. In evaluating the causes of a retrobulbar hemorrhage, one must consider the possibility of a needle injury to an extraocular muscle.


Enzyme immunoassays for the estimation of adenosine 3',5' cyclic monophosphate and guanosine 3',5' cyclic monophosphate in biological fluids.
Simple, rapid and sensitive competitive enzyme immunoassays for the estimation of adenosine 3',5' cyclic monophosphate (cAMP) and guanosine 3',5' cyclic monophosphate (cGMP) in human plasma and urine are described. Specific antisera to each nucleotide were raised in rabbits by immunization with succinyl cyclic nucleotide--human serum albumin conjugates. For the assay, specific antibodies were incubated with a mixture of succinyl cyclic nucleotide labelled with horseradish peroxidase together with unlabelled standard or sample. The antibody-bound enzyme conjugate was separated from free hapten by anti-rabbit (IgG) sera immobilized to a microtitre plate. Activity of the bound enzyme conjugate was determined with tetramethylbenzidine. The assays were capable of detecting levels as low as 2 fmol of cAMP and cGMP. Good correlations were obtained between values generated by enzyme immunoassay and radioimmunoassay.


Incorporating Laboratory Animal Science into Responsible Biomedical Research.
Biomedical research has made great strides in the past century leading to rapid advances in human life expectancy, all derived from improved understanding, prevention, and treatment of many diseases and conditions. Research involving laboratory animals has played a significant role in this medical progress. However, there continues to be controversy surrounding the use of animals in research, and animal models have been questioned regarding their relevance to human conditions. While research fraud and questionable research practices could potentially contribute to this problem, we argue that a relative ignorance of laboratory animal science has contributed to the "uncontrolled vivarium experiment" that runs parallel to the more controlled scientific experiment. Several variables are discussed, including husbandry, animal environment, social housing, and more, that can contribute to this uncontrolled experiment, and that can simultaneously decrease quality of life for rodent test subjects when ignored. An argument is put forward that laboratory animal veterinarians and scientists can and should play an important role in better controlling such variables. Similarly, the laboratory animal veterinarian and scientist should play an important role in responsible science by addressing complex interdisciplinary challenges.


[Aged woman's vulnerability related to AIDS].
This article is a systhematic literature review including the period from 1994 to 2009, whose objective was to discuss the aged woman's vulnerability in relation to Acquired Imunodeficiency Syndrome (Aids). The search for scientific texts was accomplished in the following databases: Biblioteca Virtual em Saúde, Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE). The descriptors used were vulnerability, woman and Aids. Eighteen texts were analyzed, including articles in scientific journals, thesis and dissertations. As a conclusion, it was noted that aged women and vulnerability to Aids are directly related, through gender characteristics including submission and that were built historical and socially. We consider as fundamental the development of studies which may generate publications accessible to women, in order to help them see themselves as persons vulnerable to Aids contagion just for being women.


Chronic kidney disease: the global challenge.
The worldwide rise in the number of patients with chronic kidney disease (CKD) and consequent end-stage renal failure necessitating renal replacement therapy is threatening to reach epidemic proportions over the next decade, and only a small number of countries have robust economies able to meet the challenges posed. A change in global approach to CKD from treatment of end-stage renal disease (ESRD) to much more aggressive primary and secondary prevention is therefore imperative. In this Seminar, we examine the epidemiology of CKD worldwide, with emphasis on early detection and prevention, and the feasibility of methods for detection and primary prevention of CKD. We also review the risk factors and markers of progressive CKD. We explore current understanding of the mechanisms underlying renal scarring leading to ESRD to inform on current and future interventions as well as evidence relating to interventions to slow the progression of CKD. Finally, we make strategic recommendations based on future research to stem the worldwide growth of CKD. Consideration is given to health economics. A global and concerted approach to CKD must be adopted in both more and less developed countries to avoid a major catastrophe.