The effect of diet on the fatty acid compositions of serum, brain, brain mitochondria and myelin in the rat.
1. Three groups of female rats (8-12 weeks old) were maintained respectively on a linoleic acid-rich diet, a linoleic acid-poor predominantly saturated-fatty acid diet and a normal diet. Changes in the fatty acid compositions of serum, brain, brain mitochondria-rich fraction and myelin were observed. 2. Of the serum fatty acids, linoleic acid showed the greatest change in the percentage of the total acids in response to diet; the change in the proportion of oleic acid was considerable. The percentages of arachidonic acid in serum fatty acids in the groups on the linoleic acid-rich and linoleic acid-poor diets were similar, but higher than those in the normal group. 3. Changes in the proportions of linoleic acid, arachidonic acid and docosahexaenoic acid occurred in brain fatty acids that to some extent paralleled those occurring in the serum. Changes in the proportions of most other acids in the serum fatty acids were not accompanied by corresponding changes in the brain fatty acids. 4. The percentage fatty acid compositions of a mitochondria-rich fraction and myelin are given, and changes in the relative proportions of linoleic acid, arachidonic acid and possibly some docosapolyenoic acids were demonstrated to occur as a result of diet. 5. The results are discussed in relation to the possible aetiology of multiple sclerosis.


Differential Effects of Message Framing on Obesity Policy Support Between Democrats and Republicans.
This study tests whether gain- and loss-framed messages about establishing obesity-reducing policies have different persuasive effects on Republicans and Democrats. In a randomized between-subject experiment, participants (N = 384) read a message emphasizing either benefits to a society by establishing policies aimed to reduce obesity (i.e., gain-framed message) or costs to a society that fails to establish those policies (i.e., loss-framed message). Results indicated that Democrats perceived the gain-framed message as more persuasive than the loss-framed message and the perceived argument strength fully mediated the framing effect on Democrats' policy support; however, there was no framing effect on perceived argument strength among Republicans. On the other hand, the gain-framed message led Republicans to attribute the cause of obesity less to the individual level compared to the loss-framed message and the no-message condition. We observed no framing difference among Democrats on causal attributions. Theoretical and practical implications of these findings are discussed.


Concerted regulation of lysine and threonine synthesis in tobacco plants expressing bacterial feedback-insensitive aspartate kinase and dihydrodipicolinate synthase.
The essential amino acids lysine and threonine are synthesized in higher plants by two separate branches of a common pathway. This pathway is primarily regulated by three key enzymes, namely aspartate kinase (AK), dihydrodipicolinate synthase (DHPS) and homoserine dehydrogenase (HSD), but how these enzymes operate in concert is as yet unknown. Addressing this issue, we have expressed in transgenic tobacco plants high levels of bacterial AK and DHPS, which are much less sensitive to feedback inhibition by lysine and threonine than their plant counterparts. Such expression of the bacterial DHPS by itself resulted in a substantial overproduction of lysine, whereas plants expressing only the bacterial AK overproduced threonine. When both bacterial enzymes were expressed in the same plant, the level of free lysine exceeded by far the level obtained by the bacterial DHPS alone. This increase, however, was accompanied by a significant reduction in threonine accumulation compared to plants expressing the bacterial AK alone. Our results suggested that in tobacco plants the synthesis of both lysine and threonine is under a concerted regulation exerted by AK, DHPS, and possibly also by HSD. We propose that the balance between lysine and threonine synthesis is determined by competition between DHPS and HSD on limiting amounts of their common substrate 3-aspartic semialdehyde, whose level, in turn, is determined primarily by the activity of AK. The potential of this molecular approach to increase the nutritional quality of plants is discussed.


Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods.
ADME (absorption, distribution, metabolism, elimination) has rapidly evolved over the past two decades, creating a unique interdisciplinary interface between medicinal chemists, biologists, formulators, toxicologists, clinicians, and regulators across industries, but has advanced most rapidly in the pharmaceutical industry. The implementation of ADME profiling of drug candidates, in conjunction with biological efficacy and safety optimization, has dramatically reduced pharmacokinetic drug failures in clinical trials and has become a lingua franca between disciplines that are involved in drug development. This article briefly reviews the basics and current state-of-the-art of ADME and the major lessons from the pharmaceutical industry on its efficient use, points out the importance of defining ADME properties leading to toxicity across industries for safety and toxicity prediction of chemicals, and raises the issues of quality, reliability, and reproducibility of tests and inclusion of ADME under the umbrella of evidence-based toxicology. Increasingly, in vitro results are used to inform ADME assessments and computer modeling. The aspects of kinetics of substances in cellular models themselves, however, are still too often neglected. ADME information will play a critical role in establishing quantitative in vitro to in vivo extrapolations (QIVIVE), integrated testing strategies, and systems toxicology approaches.


H Cotransports in Corn Roots as Related to the Surface pH Shift Induced by Active H Excretion.
The surface pH shift induced by active H(+) excretion in corn (Zea mays L.) roots was estimated using acetic acid influx as a pH probe (H Sentenac, C Grignon 1987 Plant Physiol 84: 1367-1372). At constant bulk pH, buffering the medium strongly reduced the magnitude of the surface pH shift. This was used to study the effect of surface pH shift on H(+) cotransports. In the absence of buffers, the surface pH shift increased with the bulk pH. Buffers decreased (32)Pi influx and this effect was stronger at pH 7.2 than at pH 5.8, and stronger in the absence than in the presence of an inhibitor of the proton pump (vanadate). Buffers exerted a similar depressive and pH-dependent effect on net NO(3) (-) uptake. They hyperpolarized the cell membrane, and stimulated (86)Rb(+) influx, K(+):H(+) net exchange, and malate accumulation. These results are consistent with the hypothesis that H(+) accumulation at the cell surface is effective in driving H(+) reentry. We concluded that the surface pH shift due to proton pump activity is involved in the energetic coupling of H(+) cotransports.


Directing pluripotent cell differentiation using "diced RNA" in transient transfection.
Embryonic stem (ES) and embryonic carcinoma (EC) cells are pluripotent and have the capacity to differentiate into many cell types. The ability to direct their differentiation should have considerable practical applications. Here, we first report the use of diced short interfering RNAi against Oct4 in a transient approach, to direct differentiation of ES towards the trophectoderm lineage. We then apply this approach to downregulate Smad4 in mouse P19 EC cells. We have found that this leads to an increase in the levels of Pax6 (a neuroectoderm marker), reduction in the levels of Brachyury (a mesoderm marker), and a 3-fold increase in the number of betaIII tubulin-positive colonies when these cells were allowed to differentiate. This indicates a redirection of cell fate towards the neuroectoderm lineage. Thus, transient RNAi could provide a valuable tool to direct pluripotent cells along specific pathways of differentiation while circumventing permanent genetic changes.


Effects of Moringa oleifera aqueous leaf extract in alloxan induced diabetic mice.
There is a lack of knowledge regarding the underlying mechanisms of the antidiabetic activity of Moringa oleifera. This study investigates the antidiabetic effect of M. oleifera and its impact on the immune tolerance. Alloxan-induced diabetes model for mice was used. A dose of 100 mg/kg of Moringa extract was orally administered to diabetic treated mice. Glucose and insulin levels were evaluated to calculate insulin resistance. Total antioxidant capacity (TAC), creatinine, and blood urea nitrogen (BUN) levels were measured. The relative percentage of CD44, CD69, and IFN-γ was investigated by flow cytometry. In diabetic mice, insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) was increased 4.5-fold than in the control group, and HOMA-IR was decreased 1.3-fold in the Moringa treatment group. The level of TAC was declined 1.94-fold in diabetic mice, and increased 1.67-fold in diabetic treated group. In diabetic mice, creatinine and BUN levels were significantly reduced 1.42- and 1.2-fold, respectively, in Moringa treatment mice. The relative percentage of CD44 was not changed in diabetic mice, but the relative percentage of CD69 was found to be increased. INF-γ was decreased 2.4-fold in diabetic mice and elevated in treated groups. Moringa may ameliorate insulin resistance, increase TAC, and improve immune tolerance.


HACCP approach to ensure the safety and quality of food packaging.
EC Directive 93/43/EEC of 14 June 1993 on the hygiene of foodstuffs has been implemented in the Netherlands through the Food and Commodity Act (Warenwet) of 14 December 1995. This Directive requires food companies to identify steps in their activities that are critical to ensuring food safety, and to ensure that adequate safety procedures are identified, implemented, maintained and reviewed based on the principles of the Hazard Analysis Critical Control Point (HACCP) system. HACCP is a tool used to assess hazards, estimate risks and establish specific control measures that emphasize prevention and control rather than reliance on end-product testing. Increasing public awareness of food safety, together with the introduction of this new legislation, has led producers and retailers of food to demand higher standards from their suppliers. Suppliers of raw materials, ingredients and also food packaging will be expected to bring their standards of hygiene in line with the expectations of the food industry. Food producers will need to obtain the guarantee from their suppliers that the packaging does not negatively influence their products. HACCP is a method that can also be applied to ensure the safety and other quality aspects of all kinds of food packaging materials such as films, foils, trays, cups, boxes and tubs made of paper, cardboard, polymers, metal and other materials (single use or disposable packagings as well as re-usable and recycled packagings). At the Netherlands Organization for Applied Scientific Research (TNO), the quality and safety aspects of re-use of food packaging, and refillable bottles in particular, have been the subject of extensive investigations in the project 'Quality monitoring of synthetic refillable bottles'. In this paper the set-up of the project and the Codes of Practice for refillable bottles are described. Moreover, the applicability of HACCP to food packagings and an example of a HACCP study for refillable PET bottles will be discussed.


Diagnosis and follow-up of glycogen storage disease (GSD) type VI from the largest GSD center in China.
Glycogen storage disease (GSD) Type VI is a glycogenolysis disorder caused by variants of PYGL. Knowledge about this disease is limited because only approximately 50 cases have been reported. We investigated the clinical profiles, molecular diagnosis, and treatment outcomes in patients with GSD VI from 2000 to 2021. The main initial clinical features of this cohort include hepatomegaly, short stature, elevated liver transaminases, hypertriglyceridemia, fasting hypoglycemia, and hyperuricemia. After uncooked cornstarch treatment, the stature and biochemical parameters improved significantly (p < 0.05). However, hyperuricemia recurred in most patients during adolescence. Among the 56 GSD VI patients, 54 biallelic variants and two single allelic variants of PYGL were identified, of which 43 were novel. There were two hotspot variants, c.1621-258_2178-23del and c.2467C>T p.(Gln823*), mainly in patients from Southwest and South China. c.1621-258_2178-23del is a 3.6 kb deletion that results in an out-of-frame deletion r.1621_2177del and an in-frame deletion r.1621_2265del. Our data show for the first time that long-term monitoring of uric acid is recommended for older GSD VI patients. This study also broadens the variant spectrum of PYGL and indicates that there are two hot-spot variants in China.


Magnesium-sensing riboswitches in bacteria.
All living organisms require mechanisms for coordination of intracellular metal concentrations. Many types of metal-sensing regulatory proteins have been described previously. Data in recent years have revealed that posttranscriptional mechanisms are also utilized for control of metal ion homeostasis in bacteria. In particular, two classes of RNA structural elements have been discovered to coordinate magnesium-induced structural transitions with expression levels of downstream genes. We discuss these types of regulatory RNAs herein and compare them to other classes of riboswitches that respond instead to small organic metabolites.


Effects of the alkali-metal cation size on molecular and extended structures: formation of coordination polymers and hybrid materials in the homologous series [(4-Et-C6H4OM)·(diox)n], M = Li, Na, K, Rb, Cs.
The complete series of group 1 metal 4-ethylphenoxide (4-Et-C(6)H(4)O(-)) networks have been synthesized using 1,4-dioxane (diox) as a neutral linker. [{(4-Et-C(6)H(4)OLi)(4)·(diox)(2.5)}·diox](∞) (1) and [{(4-Et-C(6)H(4)ONa)(6)·(diox)(3)}(∞)] (2) form 2D and 3D networks, respectively, composed of discrete aggregates linked by diox. Compound 1 forms a hexagonal layered structure with Li(4)O(4) cubanes acting as nodes, whereas compound 2 forms a primitive cubic network (pcu) with Na(6)O(6) hexameric nodes. [{(4-Et-C(6)H(4)OK)(3)·diox}(∞)] (3), [{(4-Et-C(6)H(4)ORb)(2)·(diox)(0.5)}(∞)] (4), and [{(4-Et-C(6)H(4)OCs)(2)·(diox)(0.5)}(∞)] (5) are composed of isostructural 1D inorganic rods that are linked through diox to form pcu-type networks. Compound 5 is the first example of a network built from cesium inorganic rods.


Superior sagittal sinus thrombosis: assessment with Tc-99m labeled red blood cells.
The diagnostic value of scintigraphy with technetium-99m labeled red blood cells (Tc-RBC) was assessed in 19 patients with clinical suggestion of superior sagittal sinus thrombosis (SSST). Comparison of Tc-RBC static images with dynamic flow studies in the brain showed a sensitivity of 100%, specificity of 86%, and accuracy of 94% for static studies and values of 87%, 20%, and 61%, respectively, for the flow studies. Tc-RBC scintigraphy enables direct visualization of the integrity of the superior sagittal sinus, whereas CT scanning shows various but nonspecific changes in the brain associated with SSST. Single-photon emission CT study using Tc-RBC, performed in six patients, appears to have potential in the diagnosis of SSST, allowing separation of vascular structures that are superimposed on the superior sagittal sinus in planar scintigraphy study.


Mechanisms of microbial pathogenesis and the role of the skin microbiome in psoriasis: A review.
The pathogenesis of psoriasis may involve a breakdown of immune tolerance to cutaneous microorganisms. Psoriasis is associated with a higher incidence of Crohn disease and periodontitis, two diseases involving impaired tolerance and abnormal immune activation in response to intestinal and oral microbiota, respectively. In addition, guttate and chronic plaque psoriasis are associated with Streptococcus pyogenes colonization. The aim of this review is to characterize the microorganisms implicated in psoriasis by examining results of major association studies and possible mechanisms of pathogenesis. Although studies show relative increases in Streptococcus and Staphylococcus and decreases in Malassezia and Cutibacterium, they differ in methods of sampling and methods of microbial analysis. As such, no definitive associations between microbes and psoriasis have been found to date. It also remains unclear if changes in the microbiomal composition have a causal association with psoriasis or are simply a consequence of the inflammatory microenvironment. Techniques enabling strain-level analysis rather than species-level analysis of the skin microbiome are likely necessary to determine microbiomal signatures of psoriasis. Future investigations may lead to new diagnostic tests and novel treatments, such as probiotics or bacterial transplantation.


Evaluation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery.
Implementation of point-of-care tests is recommended to provide tailored substitution during cardiac surgery. The measurement and substitution of fibrinogen have gained particular interest since it is the first coagulation factor to become depleted during cardiac surgery. However, the prognostic ability of thromboelastography (TEG) 6s has not been evaluated in pediatric patients. The aim of the present study was to describe patient characteristics of infants receiving fibrinogen substitution during cardiac surgery and evaluate the prognostic ability of TEG6s after weaning off cardiopulmonary bypass (CPB). Infants undergoing congenital cardiac surgery with CPB were retrospectively included (n = 279) between January 2017 to July 2019. Patient and perioperative data were collected on the day of surgery until 6:00 AM the next morning. Hemostatic capacity was assessed with TEG6s. The efficacy of TEG-functional fibrinogen-maximal amplitude (TEG-FF-MA) measurements for the prediction of intraoperative bleeding, and thereby cryoprecipitate need, was evaluated by a sensitivity and specificity analysis. Among 174 children with TEG-FF-MA data, 147 (84%) received cryoprecipitate intraoperatively. Cryoprecipitate administration was associated with younger age 66 (10-132) versus 98 (45-204) days (p = .044), higher RACHS-1 classification, and intraoperative bleeding 21 (11-47) versus 5 (3-13) ml/kg (p < .001, mean difference 29 ml/kg [CI: 8-50]). Median TEG-FF-MA values were lower in transfused children 7.6 (5.3-11.0) versus 10.5 (7.3-13.4) mm (p = .004, mean difference - 2.4 mm [CI: -4.1 to - 0.73]). The volume of cryoprecipitate was associated with bypass time, TEG-FF-MA values, and in particular intraoperative bleeding volumes. A TEG-FF-MA threshold of 10.0 mm, resulted in sensitivity: 74%, specificity: 56%, positive predictive value: 80%, and a negative predictive value of 47% for the prediction of intraoperative bleeding (>10 ml/kg) and consequently a need of cryoprecipitate transfusion. Fibrinogen substitution in infants was associated with younger age and higher RACHS-1 category. The prognostic value of TEG6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undertaken congenital heart surgery.


Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.
Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat. Rats were exposed to 60-min middle cerebral artery (MCA) occlusion. Vehicle and non-hypotensive doses of candesartan (0.1 mg/kg) were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability. The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption (Evans blue extravasation = 12.5 ± 1.94 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%). Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.


The relative importance of transcriptional and post transcriptional regulation of Drosophila chorion gene expression during oogenesis.
To determine the relative roles of transcriptional and post-transcriptional events in establishing the temporal pattern of chorion gene expression in Drosophila, we have examined chorion gene transcription, RNA accumulation, and protein synthesis in follicles of selected pre-, early-, and late-choriogenic stages. Chorion gene transcription was assayed in follicle cell nuclei by nuclear run-on reactions. For the s15, s16, s18, s36, and s38 chorion genes, the periods of intense transcription are as predicted from the dynamics of RNA accumulation and protein synthesis, indicating that these genes are primarily regulated at the transcriptional level. In contrast, gene s19 appears subject to post-transcriptional control at stage 14, when transcription rates are substantially higher than predicted from the observed RNA levels. Transcription of regions between the clustered and tandemly oriented chorion genes was also examined. In contrast to many RNA polymerase II transcribed genes, for the s18 and s36 chorion genes run-on transcription appears to terminate within about 100 base pairs downstream of the polyadenylation sites, corroborating previous reports based on electron microscopy of s36 [Osheim et al., EMBO J 5:3591-3596, 1986].


Unequal selves in the classroom: Nature, origins, and consequences of socioeconomic disparities in children's self-views.
Children from low socioeconomic status (SES) backgrounds often have more negative self-views than their peers. How are these self-views shaped by teacher-student interactions in the classroom, and what are the consequences of these self-views for achievement inequality? We present a developmental framework addressing these questions by bridging insights from the psychological, educational, and sociological literatures. We show that children from low-SES backgrounds perceive themselves as less intelligent, less able to grow their intelligence, less deserving, and less worthy, independent of their actual abilities and achievements. We demonstrate how negative intellectual stereotypes-expressed through daily interactions with teachers in classrooms, such as teachers' expectations, feedback, and attention-undercut the self-views of children from low-SES backgrounds. We also show how this process can be exacerbated by institutional and cultural values reflecting a belief in meritocracy (e.g., schools that encourage competition, emphasize raw ability, and attribute achievement inequality to intrinsic factors), which are common in countries with high income inequality and rigid between-school tracking. The ensuing more negative self-views introduce psychological barriers that undermine the academic achievement of children from low-SES backgrounds, thereby reinforcing achievement inequality. This represents an enormous loss of potential and perpetuates harm into adulthood. Socioeconomic disparities in self-views can emerge early in life and widen with age, underlining the need for developmental research and timely intervention. We discuss implications for studying the nature, origins, and consequences of socioeconomic disparities in self-views, and for designing interventions to reduce achievement inequality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Cryptosporidium Spp., a frequent cause of diarrhea among children at the Korle-Bu Teaching Hospital, Accra, Ghana.
This report presents the results of a study conducted at the Child Health Department, Korle-Bu Teaching Hospital, Accra, Ghana, between the months of October 2001 and June 2002. Stool samples from 227 children with diarrhea and 77 children without diarrhea, aged less than 5 years, were tested for Cryptosporidium spp. Prevalence rates were 27.8 and 15.6% in children with and without diarrhea, respectively. Cryptosporidium infection was found to be high in children between the ages of 6 and 24 months. Cryptosporidium spp. was more common in malnourished children, but was not isolated in children under 6 months of age who were exclusively breastfed. Neither the presence of domestic animals, abdominal pain, blood in stool, nausea, vomiting, nor the consumption of untreated water was associated with Cryptosporidium spp. infection. Shigella, Salmonella, and yeast-like organisms were the most frequently identified enteropathogenic bacteria. In summary, this study demonstrates the prevalence of Cryptosporidium spp. among Ghanaian children.


A randomized trial of 48 versus 24 weeks of combination pegylated interferon and ribavirin therapy in genotype 6 chronic hepatitis C.
Genotype 6 chronic hepatitis C (HCV) is encountered predominantly in Southeast Asia and data on optimal treatment strategy is limited. This study was aimed at assessing the rate and predictors of sustained virological response (SVR) in genotype 6 chronic HCV following 48 and 24 weeks of pegylated interferon and ribavirin therapy. This investigator-initiated, open-label randomized trial was conducted in Vietnam between 2008 and 2010. One hundred and five treatment-naïve HCV genotype 6 patients were randomized to either 48-week (N=70) or 24-week (N=35) duration of pegylated interferon (PEG-IFN) alfa-2a 180 mcg/week and ribavirin (RBV) 15mg/kg/day; 92 patients completed the study (63 in the 48-week and 29 in the 24-week group, respectively). Primary outcome was sustained virological response (SVR) as intention-to-treat analysis. There was no statistical difference in SVR between 48-week and 24-week treated groups (71% vs. 60%, respectively; p=0.24). In the 48-week and 24-week treatment groups, 81% and 80% of cases achieved rapid virological response (RVR) (p=0.86), and 86% and 80% achieved complete early virological response (p=0.45). Among those patients with RVR, SVR was in 86% (48-weeks), and 75% (24-weeks) of cases, whereas following non-RVR, only 8% of cases had an SVR with 48-week treatment duration. Overall, RVR was achieved in the majority of genotype 6 patients and, in those patients, similar and high rates of SVR were noted following 24-week and 48-week therapy. This observation, however, needs validation in a larger study to demonstrate non-inferiority of the shorter duration therapy. In non-RVR patients, even 48-week therapy achieved low SVR rates.


Short-range Ising spin glasses: the metastate interpretation of replica symmetry breaking.
Parisi's formal replica-symmetry-breaking (RSB) scheme for mean-field spin glasses has long been interpreted in terms of many pure states organized ultrametrically. However, the early version of this interpretation, as applied to the short-range Edwards-Anderson model, runs into problems because as shown by Newman and Stein (NS) it does not allow for chaotic size dependence, and predicts non-self-averaging that cannot occur. NS proposed the concept of the metastate (a probability distribution over infinite-size Gibbs states in a given sample that captures the effects of chaotic size dependence) and a nonstandard interpretation of the RSB results in which the metastate is nontrivial and is responsible for what was called non-self-averaging. In this picture, each state drawn from the metastate has the ultrametric properties of the old theory, but when the state is averaged using the metastate, the resulting mixed state has little structure. This picture was constructed so as to agree both with the earlier RSB results and with rigorous results. Here we use the effective field theory of RSB, in conjunction with the rigorous definitions of pure states and the metastate in infinite-size systems, to show that the nonstandard picture follows directly from the RSB mean-field theory. In addition, the metastate-averaged state possesses power-law correlations throughout the low-temperature phase; the corresponding exponent ζ takes the value 4 according to the field theory in high dimensions d, and describes the effective fractal dimension of clusters of spins. Further, the logarithm of the number of pure states in the decomposition of the metastate-averaged state that can be distinguished if only correlations in a window of size W can be observed is of order W(d-ζ). These results extend the nonstandard picture quantitatively; we show that arguments against this scenario are inconclusive. More generally, in terms of Parisi's function q(x), if q(0)≠∫(0)(1)dxq(x), then the metastate is nontrivial. In an Appendix, we also prove rigorously that the metastate-averaged state of the Sherrington-Kirkpatrick model is a uniform distribution on all spin configurations at all temperatures.


An overview of the understanding of ions containing solely fluorine atoms.
We discuss in the current paper ions containing solely fluorine atoms, F-, F2- and F3-, their corresponding cationic and/or multiply charged counterparts. While the emphasis of the paper is on gas phase species, their energetics and reactions, aqueous solutions are also discussed. In particular, biomedical and analytical aspects of F- are also considered. The new trichotomy of convenience, anthropocentrism and folksonomy is also applied to the understanding of our fluorine-containing ions.


The effect of standardized honey on mucosal healing of the nose and paranasal sinuses after polypectomy: A randomized controlled, double blind pilot study.
Nasal polyposis (NP) is a chronic inflammatory disease. Honey has several anti-microbial, anti-oxidants, healing, and anti-inflammatory properties which may reduce the need for steroids in this situation. Therefore, the aim of this study is to show the effect of standardized honey on mucosal healing of the nose and paranasal sinuses after polypectomy. In this double-blind, randomized, placebo-controlled clinical trial, 28 patients with nasal polyposis underwent functional endoscopic sinus surgery (FESS). Besides common post-op medications, normal saline (as a placebo) and diluted processed honey were used separately in the two nostrils of each patient. Two endoscopic follow-ups using the Philppot-Javer (P-J) scoring system were performed to assess the healing and recurrence of polyps on either side. The secondary outcome measure was the patients' satisfaction rate. The patients' mean age was 38.03±11.9 years. 15(57.7%) had a positive prick test and also 15(57.7%) had dense eosinophilic infiltration in their surgical specimens. In the first and second follow-up sessions, total P-J scores showed better results for honey in comparison to the normal saline side but that results were not significantly different (P=0.93, P=0.07); whereas it is fair to say that in the second follow-up, the ethmoid and maxillary sinuses demonstrated a greater difference compared to the other sites based on their averages but there were not significantly meaningful (P=0.05, P=0.06). The total score also showed better results for honey in comparison to the normal saline side but was statistically insignificant (P=0.07). Diluted honey seems to have certain positive effects in reducing post-operative edema and the recurrence of nasal polyps in at least the ethmoid and maxillary sinuses; although this positive effect did not result in significant changes. (www.actabiomedica.it).


HLA typing using IL-2 activated T lymphocytes: usefulness in pediatric candidates for allogeneic bone marrow transplantation.
Following a preliminary study in healthy blood donors, we have performed serological HLA-A, B, C, DR and DQ typing using recombinant IL-2 activated T lymphocytes (IL-2.aTLs) in pediatric candidates for allogeneic bone marrow transplantation. In such patients, it is often difficult to obtain the quantity of lymphocytes required for HLA typing, particularly for class II typing using B lymphocytes, considering the timing of sampling and the volume of blood to be collected. Peripheral blood mononuclear cells (PBMCs) were activated and expanded with IL-2 until a sufficient number of IL-2.aTLs of good viability were available for the typing. In the first 10 cases, analyses of surface markers (CD2, CD20, CD25, CD36, HLA-DR and HLA-DQ, CD2/HLA-DR: two color) of IL-2.aTLs were done using flow cytometry at the time of HLA typing and indicated that IL-2.aTLs expressed HLA-DR and DQ antigens sufficient for evaluation. A small number (less than 10(6] of fresh or cryopreserved PBMCs, even those containing leukemic blast cells, were sufficient to induce and expand IL-2.aTLs for HLA typing. To date we have been able to successfully HLA-A, B, C, DR and DQ type 20/20 pediatric candidates. The HLA antigens identified on the patients' IL-2.aTLs were confirmed by a family study.


Effect of valvular heart diseases, migraine headaches, and perianal diseases on the risk of involvement in motor vehicle crashes.
Impaired health can interfere with driving performance. We have launched this investigation to identify in professional military drivers health parameters that might be associated with involvement in motor vehicle crashes (MVCs). All Israel Defense Forces professional male drivers (N = 5,605) conscripted into compulsory military service between April 1, 1988 and April 1, 1990 were divided into two groups according to whether (N = 1,300) or not (N = 4,305) the driver was involved in MVCs during the same time frame. Using the multivariate Cox model, a significant association was shown between involvement in MVCs and the following health parameters: mild-to-moderate valvular heart disease (p = 0.0002, chi 2 = 13.89), migraine headaches (p = 0.009, chi 2 = 6.91), and perianal diseases (p = 0.006, chi 2 = 7.44). We hypothesize that interference with the driver's performance level may be a result of the discomfort associated with those clinical conditions. It is possible that interference with the personal performance level decreased the ability of the driver to cope with the specific driving task demands and resulted in the involvement of the driver in MVCs. We suggest that because of the high social and economic costs associated with road accidents, it is important to investigate further the association of involvement in MVCs and health problems. If our findings are confirmed in the future studies, intervention programs to reduce MVC rates would be suggested and conducted among professional drivers.


Structures of heterogeneous proton-bond dimers with a high dipole moment monomer: covalent vs electrostatic interactions.
A number of calculated structures of heterogeneous proton-bound dimers containing monomers such as acetonitrile, cyanamide, vinylene carbonate, and propiolactone, which have high dipole moments, are presented. These proton-bound dimers are predicted to have a structural anomaly pertaining to the bond distances between the central proton and the basic sites on each of the monomers. The monomers with the high dipole moments also have the larger proton affinity and, on the basis of difference in proton affinities, it would be expected that the proton would be closer to this monomer than the one with the lower proton affinity. However, the proton is found to lie substantially closer to the monomer with the lower proton affinity in most cases, unless the difference in proton affinity is too large. Simply stated, the difference in proton affinities is smaller than the difference in the affinity to form an ion-dipole complex for the two monomers and it is the larger affinity for the high dipole moment monomer (which also has the higher proton affinity) to form an ion-dipole complex that is responsible for the proton lying closer to the low proton affinity monomer. The bond distances between the central proton and the monomers are found to be related to the difference in proton affinity. It is found, though, that the proton-bound dimers can be grouped into two separate groups, one where the proton-bound dimer contains a high dipole moment monomer and one group where the proton-bound dimer does not contain a high dipole moment monomer. From these plots it has been determined that a high dipole moment monomer is one that has a dipole moment greater than 2.9 D.


Bradykinin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity.
Activation of the kallikrein-kinin system in lung injury has long been recognized. However, the effects of bradykinin (BK) on human lung fibroblasts (HLF) remain to be elucidated. We determined whether BK stimulates HLF to release chemotactic activity for neutrophils and monocytes (NCA and MCA, respectively). We evaluated HLF supernatant fluids for chemotactic activity through a blind-well chamber technique. HLF released NCA and MCA in a dose- and time-dependent manner in response to BK. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by a leukotriene (LT) B(4) receptor antagonist and by antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF). MCA was attenuated by the LTB(4) receptor antagonist and by antibodies to monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-beta. Both the LTB(4) receptor antagonist and these antibodies inhibited chemotactic activity of the molecular weights corresponding to MCP-1, GM-CSF, and TGF-beta, separated by column chromatography. The concentrations of IL-8, G-CSF, MCP-1, GM-CSF, and TGF-beta in supernatant fluids increased significantly in a time-dependent manner in response to BK. The receptors responsible for the release of NCA, MCA, and individual chemokines included both BKB(1) and BKB(2) receptors. These data suggest that BK may stimulate lung fibroblasts to release inflammatory cytokines, which may modulate lung inflammation.


Introducing porosity into polyimide nanoparticles.
Novel porous polyimides (PIs) having diameters of several hundred nanometers have been fabricated successfully from precursor poly(amic acid) (PAA) derivatives with poly(acrylic acid) (PAS) as the porogen, using a reprecipitation method and subsequent imidization. The superficial high porosity with deep pores was introduced when using a more compatible combination of PAA and the porogen, i.e., PI (BPDA-PDA) and PAS rather than PI (10FEDA-4FMPD and PAS); the pore sizes ranged from 20 to 100 nm. The resulting porous PI nanoparticles had thermally stabilities (determined from their 5% weight loss temperatures at 400 degrees C) similar to those of corresponding PI nanoparticles lacking porous structures. Microphase separation within the PAA nanoparticles after reprecipitation induced the porous surface structure, the properties of which were influenced by the molecular weight of PAS and the chemical structure of PAA. These unique porous PI nanoparticles have great potential for application as low-k materials in next-generation technologies.


Impact of choice of coping strategies and family functioning on psychosocial function of young people with epilepsy.
Both medical and psychological factors have an important impact upon the psychosocial functioning of young people with epilepsy. The purpose of this study was to identify factors that distinguish young people with epilepsy and high psychosocial functioning from those with lower levels. The participants were 114 young people (40 males, 74 females) with active epilepsy and a mean age of 17.92years (SD=3.90) who completed either a paper (60.5%) or a web-based survey (39.5%) comprising demographic, medical, and psychosocial measures. Psychosocial measures included family functioning, adolescent coping, anxiety, depression, and quality of life. A latent class analysis produced two psychosocial functioning groups based on participants' scores for anxiety, depression, and quality of life. Young people were more likely to be members of the group with poor psychosocial functioning if they had a seizure in the last month (Wald=5.63, p<.05), came from families with lower levels of communication and problem solving (Wald=5.28, p<.05), and made greater use of non-productive (emotion-focused) coping strategies such as wishful thinking, withdrawal, and worry (Wald=12.00, p<.01). The findings suggest that, in addition to standard medical treatment, clinicians may promote better outcomes by strengthening family functioning and encouraging less use of nonproductive coping strategies.


At the heart of tissue: endothelin system and end-organ damage.
ET (endothelin)-1 was first described as a potent vasoconstrictor. Since then, many other deleterious properties mediated via its two receptors, ETA and ETB, have been described, such as inflammation, fibrosis and hyperplasia. These effects, combined with a wide tissue distribution of the ET system, its up-regulation in pathological situations and a local autocrine/paracrine activity due to a high tissue receptor binding, make the tissue ET system a key local player in end-organ damage. Furthermore, ET-1 interacts in tissues with other systems such as the RAAS (renin-angiotensin-aldosterone system) to exert its effects. In numerous genetically modified animal models, non-specific or organ-targeted ET-1 overexpression causes intense organ damage, especially hypertrophy and fibrosis, in the absence of haemodynamic changes, confirming a local activity of the ET system. ET receptor antagonists have been shown to prevent and sometimes reverse these tissue alterations in an organ-specific manner, leading to long-term benefits and an improvement in survival in different animal models. Potential for such benefits going beyond a pure haemodynamic effect have also been suggested by clinical trial results in which ET receptor antagonism decreased the occurrence of new digital ulcers in patients with systemic sclerosis and delayed the time to clinical worsening in patients with PAH (pulmonary arterial hypertension). The tissue ET system allows therapeutic interventions to provide organ selectivity and beneficial effects in diseases associated with tissue inflammation, hypertrophy or fibrosis.


High frequency (139.5 GHz) electron paramagnetic resonance characterization of Mn(II)-H2(17)O interactions in GDP and GTP forms of p21 ras.
As a molecular switch, the ras protein p21 undergoes structural changes that couple recognition sites on the protein surface to the guanine nucleotide-divalent metal ion binding site. X-ray crystallographic studies of p21 suggest that coordination between threonine-35 and the divalent metal ion plays an important role in these conformational changes. Recent ESEEM studies of p21 in solution, however, place threonine-35 more distant from the metal and were interpreted as weak or indirect coordination of this residue. We report high frequency (139.5 GHz) EPR spectroscopy of p21.Mn(II) complexes of two guanine nucleotides that probes the link between threonine-35 and the divalent metal ion. By analysis of high-frequency EPR spectra, we determine the number of water molecules in the first coordination sphere of the manganous ion to be four in p21.Mn(II).GDP, consistent with prior low-frequency EPR and X-ray crystallographic studies. In the complex of p21 with a GTP analog, p21.Mn(II).GMPPNP, we determine the hydration number to be 2, also consistent with crystal structures. This result rules out indirect coordination of threonine-35 in the solution structure of p21.Mn(II).GMPPNP, and implicates direct, weak coordination of this residue as suggested by Halkides et al. [(1994) Biochemistry 33,4019]. The 17O hyperfine coupling constant of H2(17)O is determined as 0.25 mT in the GDP from and 0.28 mT in the GTP form. These values are similar to reported values for 17O-enriched aquo ligands and some phosphato ligands in Mn(II) complexes. The high magnetic field strength (4.9 T) employed in these 139.5 GHz EPR measurements leads to a narrowing of the Mn(II) EPR lines that facilitates the determination of 17O hyperfine interactions.


Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics.
We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.


The treatment targets of asthma: from laboratory to clinic.
Asthma is a chronic disease characterised by airways hyperresponsiveness, airways inflammation, airways remodelling and reversible airways obstruction. Airway structural cells, recruited inflammatory cells and many mediators such as cytokines, chemokines and adhesion molecules are involved in the pathogenesis of asthma. Although asthma is treatable in most, but not all patients by currently available drugs, no treatment is preventive or curative and the disease has reached epidemic proportions worldwide and its incidence is continuing to increase. Many thousands have chronic, severe asthma and suffer daily symptoms making it imperative that we continue to improve our understanding of the mechanisms of asthma particularly related to airway inflammation and remodelling, the hallmarks of asthma, and to identify new therapeutic targets. In this review we will discuss current drugs and potential targets in the treatment of asthma.


LncRNA XIST promotes extracellular matrix synthesis, proliferation and migration by targeting miR-29b-3p/COL1A1 in human skin fibroblasts after thermal injury.
Long noncoding RNAs (lncRNAs) have been reported to be associated with dermis process during burn wound healing. This study aimed to investigate the role of lncRNA X-inactive specific transcript (XIST) in human skin fibroblasts (HSF) and extracellular matrix (ECM) as well as the regulatory network of XIST/microRNA-29b-3p (miR-29b-3p)/collagen 1 alpha 1 (COL1A1). The wound samples were collected from 25 patients with deep partial thickness burn at day 5 after burn. The thermal injured model was established using HSF cells. The expressions of XIST, miR-29b-3p and COL1A1 were measured by quantitative real-time polymerase chain reaction and western blot. ECM synthesis, cell proliferation and migration were detected by western blot, cell counting kit-8 and trans-well assays, respectively. The interaction between miR-29b-3p and XIST or COL1A1 was explored by bioinformatics analysis and luciferase reporter assay. The expressions of XIST and COL1A1 were enhanced but miR-29b-3p expression was decreased after thermal injury. XIST overexpression promoted ECM synthesis, cell proliferation and migration in thermal injured HSF cells. However, XIST knockdown played an opposite effect. miR-29b-3p overexpression inhibited ECM synthesis, cell proliferation and migration, which was reversed by XIST. COL1A1 silence suppressed ECM synthesis, cell proliferation and migration by miR-29b-3p targeting. Moreover, COL1A1 up-regulation weakened the effect of XIST silence on ECM synthesis and HSF cell function. XIST promoted ECM synthesis, cell proliferation and migration by sponging miR-29b-3p and targeting COL1A1 in HSF cells after thermal injury, indicating the promoting role of XIST in wound healing.


Possible seasonality of Clostridium difficile in retail meat, Canada.
We previously reported Clostridium difficile in 20% of retail meat in Canada, which raised concerns about potential foodborne transmissibility. Here, we studied the genetic diversity of C. difficile in retail meats, using a broad Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence and indications of possible seasonality (highest prevalence in winter).


Skeletal myoclonus in olivopontocerebellar atrophy: treatment with trihexyphenidyl.
We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder.


Attenuation, dispersion and nonlinearity effects in graphene-based waveguides.
We simulated and analyzed in detail the behavior of ultrashort optical pulses, which are typically used in telecommunications, propagating through graphene-based nanoribbon waveguides. In this work, we showed the changes that occur in the Gaussian and hyperbolic secant input pulses due to the attenuation, high-order dispersive effects and nonlinear effects. We concluded that it is possible to control the shape of the output pulses with the value of the input signal power and the chemical potential of the graphene nanoribbon. We believe that the obtained results will be highly relevant since they can be applied to other nanophotonic devices, for example, filters, modulators, antennas, switches and other devices.


Sparganosis due to Spirometra sp. (cestoda; Diphyllobothriidae) in captive meerkats (Suricata suricatta).
We report three cases of sparganosis due to plerocercoids of the tapeworm Spirometra sp. in captive meerkats (Suricata suricatta) from a zoo exhibit in the southeastern United States. Two meerkats were euthanized, one due to an uncontrollable seizure and the other due to trauma, and at necropsy cysts containing cestode larvae were observed. A third meerkat had a subcutaneous nodule surgically removed, which contained similar larvae. The third animal died years later, and had numerous cestode larvae in the pleural and peritoneal cavities. The larvae were morphologically identified as plerocercoids of diphyllobothriidean cestodes. On necropsy, multiple nodules, ranging in size from 2.5 to 3.0 cm, were observed in the subcutaneous tissue and muscles. Multifocally, separating skeletal muscle fibers were longitudinal and transversal sections of cestode larva. Histologically, parasitic cysts contained large numbers of neutrophils and macrophages, admixed with proteinaceous material. Molecular and phylogenetic analyses confirmed that specimens from one of the meerkats belonged to the genus Spirometra and was closely related to Spirometra plerocercoids isolated from a snake from the United States and wild felids from South America. Meerkats likely became infected by ingesting infected second intermediate hosts, such as amphibians and reptiles that may have entered the exhibit. Management practices that minimize access of meerkats and other susceptible hosts to intermediate hosts should be implemented.


Dangling Bonds as Possible Contributors to Charge Noise in Silicon and Silicon-Germanium Quantum Dot Qubits.
Spin qubits based on Si and Si1-xGex quantum dot architectures exhibit among the best coherence times of competing quantum computing technologies, yet they still suffer from charge noise that limit their qubit gate fidelities. Identifying the origins of these charge fluctuations is therefore a critical step toward improving Si quantum-dot-based qubits. Here, we use hybrid functional calculations to investigate possible atomistic sources of charge noise, focusing on charge trapping at Si and Ge dangling bonds (DBs). We evaluate the role of global and local environment in the defect levels associated with DBs in Si, Ge, and Si1-xGex alloys, and consider their trapping and excitation energies within the framework of configuration coordinate diagrams. We additionally consider the influence of strain and oxidation in charge-trapping energetics by analyzing Si and GeSi DBs in SiO2 and strained Si layers in typical Si1-xGex quantum dot heterostructures. Our results identify that Ge dangling bonds are more problematic charge-trapping centers both in typical Si1-xGex alloys and associated oxidation layers, and they may be exacerbated by compositional inhomogeneities. These results suggest the importance of alloy homogeneity and possible passivation schemes for DBs in Si-based quantum dot qubits and are of general relevance to mitigating possible trap levels in other Si, Ge, and Si1-xGex-based metal-oxide-semiconductor stacks and related devices.


Benchmarking Compound Methods (CBS-QB3, CBS-APNO, G3, G4, W1BD) against the Active Thermochemical Tables: Formation Enthalpies of Radicals.
The 298.15 K formation enthalpies of 38 radicals with molecular formula CxHyOz have been computed via the atomization procedure using the five title methods. The computed formation enthalpies are then benchmarked against the values recommended in the Active Thermochemical Tables (ATcT). The accuracy of the methods have been interpreted in terms of descriptive statistics, including the mean-signed error, mean-unsigned error, maximum average deviation, 2σ uncertainties, and 2×root-mean-square-deviations (2RMSD). The results highlight the following rank order of accuracy for the methods studied G4 > G3 > W1BD > CBS-APNO > CBS-QB3. The findings of this work are also considered in light of a recent companion study, which took an identical approach to quantifying the accuracies of these methods for 48 closed-shell singlet CxHyOz compounds. A similar order of accuracies and precisions were observed therein: G3 > G4 > W1BD > CBS-APNO > CBS-QB3. Both studies highlight systematic biases/deviations from the ATcT for the methods investigated, which are discussed in some detail, with methods having clear tendencies to over- or underpredict the recommended formation enthalpies for radical and/or closed-shell CxHyOz compounds. We show that one can improve the accuracy of their computation, and simultaneously reduce the uncertainty, by taking unweighted average formation enthalpies from various combinations of methods used. The reader should note that the statistical analyses preceding these conclusions also highlight that these error cancellation effects are unique for closed-shell and radical species. By extension, these error-cancellation effects can be expected to be different for various homologous series and chemical functionalities and their closed- and open-shell subgroups. Hence, further benchmarking studies are advised for other homologous series, such that the scientists and engineers (e.g., combustion/atmospheric/astrochemical) who frequently use these methods can assign reasonable uncertainties to their computations, while simultaneously optimizing their computational costs. For CxHyOz compounds, a combination of the CBS-APNO/G3/G4 methods is shown to be quite powerful when the atomization method is employed and is capable of reproducing the ATcT to within "near-chemical-accuracy", with 2RMSD (≈95% confidence interval) values of 0.0 ± 4.34 kJ mol(-1) computed for CxHyOz radicals, 0.0 ± 4.22 kJ mol(-1) for closed-shell CxHyOz compounds, with a total uncertainty of 0.0 ± 4.27 kJ mol(-1) subsequently computed considering all 85 CxHyOz compounds. Given the performance of these methods for determination of formation enthalpies when the atomization procedure is employed, we expect isodesmic reactions involving these methods to be capable of achieving chemical accuracy, as illustrated for the case of the tert-butyl radical. We also highlight that there is still disagreement between experiment and theory for this radical, despite its significance in gas-phase chemistry. Kineticists, thermodynamicists, and chemical kinetic modellers alike are warned that the popular CBS-QB3 method is found to have particularly poor performance, with a computed 2RMSD of 0.0 ± 12.51 kJ mol(-1), indicating that one should not apply this method in isolation for formation enthalpy determination unless other error-cancellation strategies are employed.


Overextended gutta-percha and Kloroperka N-O root canal fillings. Radiographic findings after 10-17 years.
A representative sample, 55%, of the patients treated endodontically by undergraduate students in a teaching clinic during the years 1963 to 1969 were reexamined 10-17 years later. Gutta-percha/Kloroperka-NO root fillings (282), classified as having surplus material at the time of treatment, were evaluated in follow-up radiographs. In about 80% of the cases of overfilling, no excess root filling material could be traced at the reexamination. In a few cases only, the appearance of the excess material was nearly identical to that at the time of treatment, whereas the remaining overfillings (18%) showed a reduced size. Among the recorded variables only one seemed to have a major impact on the prognosis--namely, the presence or absence of an apical radiolucency at the time of treatment, indicating that infection was the important factor when failures occurred. Apical overfilling per se had little influence on the long-term healing result as judged radiographically.


Parents' judgements about young children's problems: why mothers and fathers might disagree yet still predict later outcomes.
Correlates of parents' ratings of behavioural problems were explored in a sample of 93 British families, in which mothers and fathers rated their children at the time of the fourth birthday on the Achenbach Child Behavior Checklist. As in other samples, there was moderate convergence in mothers' and fathers' total problem scores, but also signs that they were reporting different sorts of problems linked to different influences. The father's rating was primarily associated with the child's cognitive ability. The mother's rating was primarily affected by her own mental state and view of her marriage. The father's but not the mother's rating provided unique information that predicted teachers' reports of the children's problems 7 years later. In general, parents' ratings of preschool children's problems reflect particular informants' perspectives on family life.


Virus-Host Interplay Between Poly (ADP-Ribose) Polymerase 1 and Oncogenic Gammaherpesviruses.
The gammaherpesviruses, include the Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and murine gammaherpesvirus 68. They establish latent infection in the B lymphocytes and are associated with various lymphoproliferative diseases and tumors. The poly (ADP-ribose) polymerase-1 (PARP1), also called ADP-ribosyltransferase diphtheria-toxin-like 1 (ARTD1) is a nuclear enzyme that catalyzes the transfer of the ADP-ribose moiety to its target proteins and participates in important cellular activities, such as the DNA-damage response, cell death, transcription, chromatin remodeling, and inflammation. In gammaherpesvirus infection, PARP1 acts as a key regulator of the virus life cycle: lytic replication and latency. These viruses also develop various strategies to regulate PARP1, facilitating their replication. This review summarizes the roles of PARP1 in the viral life cycle as well as the viral modulation of host PARP1 activity and discusses the implications. Understanding the interactions between the PARP1 and oncogenic gammaherpesviruses may lead to the identification of effective therapeutic targets for the associated diseases.


Detection of insomnia in primary care.
Insomnia is a widespread condition with diverse presentations. Detection and diagnosis of insomnia present a particular challenge to the primary care physician. Patients seldom identify their sleep habits as the source of the complaints for which they are seeking treatment. Insomnia may be the result of many different medical or psychiatric illnesses or the side effects of medications or legal or illegal recreational drugs. Insomnia has a serious impact on daily activities and can cause serious or fatal injuries. With ever-increasing competition with sleep from 24-hour television broadcasts from hundreds of channels and the Internet, as well as more traditional distractions of late-night movies, clubs, and bars, we have become a society that sleeps 25% less than our ancestors did a century ago. We have no evidence, however, that we require less sleep than they did. This article presents strategies for detecting and diagnosing insomnia.


Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.
Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.


Plasma fibronectin: a study of 340 assays.
The authors report the results of 322 assays of plasma fibronectin. The object of this study was to specify its diagnostic contribution. The assays have been effected from February 1987 to October 1988 by the laser nephelometric method in all the hospitalized patients without exclusion. We have defined two populations on clinical diagnostic criteria into 193 control cases and 129 patients suffering from inflammatory rheumatisms or bone neoplasias. The statistical processing has been effected in the Department of Medical Computer Science. The results are as follows: The rate of plasma fibronectin is inclined to increase with age (p = 1 X 10(-4) a little higher among men than among women (p = 0.05). With regard to the other biological markers of inflammation, there was no obvious correlation with the rate of fibrin, the sedimentation rate at the first hour, or the presence of C-reactive protein. This study does not confirm the specificity of this assay in the inflammatory rheumatisms although our two populations are strictly comparable with respect to age and sex, and the clinical and biological parameters (sedimentation rate and fibrin) would allow us to discern the difference, if any, between the two populations. Plasma fibronectin assay has no diagnostic or discriminating value on a large scale.


Review article: commercialization of whole-plant systems for biomanufacturing of protein products: evolution and prospects.
Technology for enabling plants to biomanufacture nonnative proteins in commercially significant quantities has been available for just over 20 years. During that time, the agricultural world has witnessed rapid commercialization and widespread adoption of transgenic crops enhanced for agronomic performance (herbicide-tolerance, insect-resistance), while plant-made pharmaceuticals (PMPs) and plant-made industrial products (PMIPs) have been limited to experimental and small-scale commercial production. This difference in the rate of commercial implementation likely reflects the very different business-development challenges associated with 'product' technologies compared with 'enabling' ('platform') technologies. However, considerable progress has been made in advancing and refining plant-based production of proteins, both technologically and in regard to identifying optimal business prospects. This review summarizes these developments, contrasting today's technologies and prospective applications with those of the industry's formative years, and suggesting how the PM(I)P industry's evolution has generated a very positive outlook for the 'plant-made' paradigm.


Characterization of testosterone metabolism and 7-hydroxycoumarin conjugation by rat and human liver slices after storage in liquid nitrogen for 1 h up to 6 months.
1. Slices of human and rat liver were cryopreserved in 18% dimethyl sulphoxide (DMSO) and subsequently stored in liquid nitrogen for periods up to as long as 6 months. After thawing, the metabolism of testosterone to hydroxylated products and conjugation of 7-hydroxycoumarin were investigated. 2. Rat liver slices stored in liquid nitrogen for 6 months exhibited rates of formation of 7alpha-, 6beta- 16alpha- and 2alpha-hydroxytestosterone, and of androstenedione that did not differ significantly from those observed with fresh slices. 3. No formation of 2alpha-hydroxytestosterone was detected with slices of human liver. However, in contrast with the rat, human slices produced 2beta-hydroxytestosterone. The rates of formation of 7alpha-, 6beta-, 16alpha- and 2beta-hydroxytestosterone and of androstenedione by human liver slices after 6 months of storage in liquid nitrogen were 82, 71, 236, 66 and 92%, respectively, of the corresponding rates by fresh slices. 4. The rates of sulphation and glucuronidation of 7-hydroxycoumarin by slices from rat liver were 97 and 119%, respectively, of the corresponding fresh values after 6 months of storage in liquid nitrogen. 5. 7-Hydroxycoumarin glucuronidation by human liver slices was 53% of the corresponding fresh values after 6 months of storage. However, human slices showed little or no capacity to conjugate 7-hydroxycoumarin with sulphate. 6. It was demonstrated that slices of both human and rat liver can be cryopreserved and stored in liquid nitrogen for at least 6 months without major changes in their rates of metabolism of testosterone to its hydroxylated products and of 7-hydroxycoumarin conjugation. These findings further emphasize that cryopreservation of liver slices can be an effective tool in the use of biological material of limited availability.


Possible relationship between common genetic variation and white matter development in a pilot study of preterm infants.
The consequences of preterm birth are a major public health concern with high rates of ensuing multisystem morbidity, and uncertain biological mechanisms. Common genetic variation may mediate vulnerability to the insult of prematurity and provide opportunities to predict and modify risk. To gain novel biological and therapeutic insights from the integrated analysis of magnetic resonance imaging and genetic data, informed by prior knowledge. We apply our previously validated pathway-based statistical method and a novel network-based method to discover sources of common genetic variation associated with imaging features indicative of structural brain damage. Lipid pathways were highly ranked by Pathways Sparse Reduced Rank Regression in a model examining the effect of prematurity, and PPAR (peroxisome proliferator-activated receptor) signaling was the highest ranked pathway once degree of prematurity was accounted for. Within the PPAR pathway, five genes were found by Graph Guided Group Lasso to be highly associated with the phenotype: aquaporin 7 (AQP7), malic enzyme 1, NADP(+)-dependent, cytosolic (ME1), perilipin 1 (PLIN1), solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1), and acetyl-CoA acyltransferase 1 (ACAA1). Expression of four of these (ACAA1, AQP7, ME1, and SLC27A1) is controlled by a common transcription factor, early growth response 4 (EGR-4). This suggests an important role for lipid pathways in influencing development of white matter in preterm infants, and in particular a significant role for interindividual genetic variation in PPAR signaling.


Efficancy of decompressive craniectomy in treatment of severe brain injury at the Rijeka University Hospital Centre.
Decompressive Craniectomy (DC) is a treatment option for severe brain injury (SBI). This method is applied when the growth of intracranial pressure (ICP) can no longer be controlled with conservative methods. DC belongs to class III "Guidelines"--"option" which has not clear clinical certainty. They do not correspond to "Standards" (class I) in treatment protocol for SBI, which is common in most neurotraumatological centers. We have analyzed retrospectively 95 patients with SBI who were admitted to the Clinical Hospital Centre Rijeka. All patients were managed based on a protocol of current Brain Trauma Foundations (BTF) Guidelines. 39 patients underwent DC while 34 patients underwent standard craniotomy. 22 patients did not undergo any surgical procedures. In each patient we analyzed ICP changes within the first 11 days and in that way we correlated them statistically with the initial Glasgow Coma Scale (GCS) and then with Glasgow Outcome Scale (GOS), after the end of the treatment. We particularly analyzed the outcome with reference to the time of the operation and the size of DC. The standard measurement of ICP shows statistical significance in recovery in the group without DC after 5 days of intensive treatment, when the pressure is stabilized between 20-25 mm Hg. The stabilization of ICP in the DC group is observed already after 3 days of intensive treatment. Furthermore, better functional recovery according to GOS, which is statistically significant, was observed in patients who underwent DC where the area of craniectomy was larger than 25 cm2, within the first 24 hours from the time of injury. The use of DC considerably reduces the need for CT check-ups. Increase in the number of encephalocele was noted, which is to be expected considering that dural decompression is used in DC procedure. The results of our study indicate that the utilization of DC is characterized with lower mortality and better functional recovery if it is applied at an early stage of treatment and if the size of DC is satisfactory.


The IVD directive: planning for compliance.
In less than 20 months, companies will only be allowed to place in vitro diagnostic (IVD) medical devices on the European market if they bear the CE mark. For this reason, the process of ensuring compliance with CE-marking requirements on or before the end of the transition period, if not already begun, should be initiated immediately. This article discusses important compliance issues.


Molecular typing of methicillin-resistant Staphylococcus aureus strains by PCR-RFLP of SPA gene: a reference laboratory perspective.
To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains by molecular typing based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of spa gene and to assess the utility of spa genotyping over bacteriophage typing in the discrimination of the strains. Studies were undertaken on 125 MRSA strains representing the most predominant phage types and the non phage typeable strains. Strains were typed by bacteriophage typing and PCR-RFLP of spa gene. DNA sequence analysis of the amplified spa gene fragment of the representative RFLP patterns was performed using standard protocols. All the strains resistant to oxacillin were found to contain mec A gene. Fifty-two per cent of these strains were typeable by the international basic set of 23 phages. Five different PCR-RFLP patterns were observed among 125 MRSA strains. Non phage typeable strains were differentiated into four PCR-RFLP patterns. Sequencing of the spa gene from the representative strains of each RFLP pattern confirmed the length of these restriction fragments due to variation in the 24 bp and the 174 bp tandem repeats. It also revealed the presence of three new spa repeat patterns. The study demonstrates the importance of spa genotyping in the discrimination of MRSA strains, which were otherwise indistinguishable by bacteriophage typing. spa genotyping allowed differentiation of strains within a particular phage type. Nucleotide sequencing of isolates of different PCR-RFLP patterns indicated a correlation between the RFLP patterns of a variable number of tandem repeats and the phage type. The study provides valuable information on the epidemiological characterization of MRSA strains.


Nanosecond pulse electrical fields used in conjunction with multi-wall carbon nanotubes as a potential tumor treatment.
The objectives of this communication were to fabricate pure samples of multi-walled carbon nanotubes (MWCNTs) and to determine their toxicity in tumor cell lines. MWCNTs were dispersed in a concentration of the surfactant T80 that was minimally toxic. Cell-type variation in toxicity to MWCNTs was observed but was not significantly different to unexposed controls. Additionally, we investigated the increased cell killing of the pancreatic cancer cell line PANC1 when exposed to ultrashort (nanosecond) pulsed electrical fields (nsPEF) in the presence of MWCNTs as a potential form of cancer therapy. We hypothesized that the unique electronic properties of MWCNTs disrupt cell function, leading to cell death, when cells are exposed to nsPEF. We observed a 2.3-fold reduction in cell survival in cells pulsed in the presence of MWCNTs compared to pulsed controls. This study demonstrates that ultrashort pulse electrical field applications have enhanced killing effects when cells are previously grown in the presence of MWCNTs, suggesting that the electrical properties of MWCNTs play a vital role in this process and is suggestive of a synergistic interaction between these nanomaterials and electrical fields.


[Progress of studies on VEC apoptosis-inducing proteins in snake venom and its mechanism--review].
Hemorrhagic snake venom specially induces apoptosis of VEC (vascular endothelial cells). Five apoptosis-inducing proteins had been purified and characterized from crude snake venom. Two of these are L-amino acid oxidase (LAO), the others belong to metalloprotease/disintegrin family. LAO catalyzes H2O2 production by oxidizing some plasma membrane proteins of VEC, disintegrins interfere with binding of integrins with their ligands. The expression of p53 and bcl-2 increases during VEC apoptosis induced by snake venom, moreover, the mRNA of bcl-2 is spliced into two fragments. It has been proved that one of adhesion-dependent signal molecules, alphavbeta3, and one of phospholipid signal molecules, PC-PLC (phosphatidylcholine-specific phospholipase C), are involved in above apoptosis-inducing signal transudation pathway. These results throw light on finding out specific component from protein is snake venom. This component is able to induce tumor vascular endothelial cells apoptosis. This review summarized progress of research on hemorrhagic snake venoms.


Virtual communication about psychiatric intensive care units: Social actor representatives claim space on Twitter.
Psychiatric intensive care units (PICU) provide care for those with the worst phases of mental illness. What defines a PICU is often decided locally at hospitals. The aim of the present study was to explore and describe a contemporary discourse on how PICU are socially constructed from virtual discussions. An explorative and descriptive study design was applied for this qualitative inquiry using discourse methodology. The data were collected in Twitter's search string and consists of 215 Twitter postings. A framework of social actor representatives that form the discourse was established and presented in three categories: (i) hospital and agencies communicating about PICU; (ii) health-care professionals communicating about PICU; and (iii) service users and relatives communicating about PICU. Hospitals, agencies, and health-care professionals hold great power and responsibility for informing the public about PICU. Transparent and informative tweets could turn the mystery of PICU into more specific, positive portrayals.


Designing scaffolds for valvular interstitial cells: cell adhesion and function on naturally derived materials.
Valvular interstitial cells (VICs) possess many properties that make them attractive for use in the construction of a tissue-engineered valve; however, we have found that the surfaces to which VICs will adhere and spread are limited. For example, VICs adhere and spread on collagen and laminin-coated surfaces, but display altered morphology and do not proliferate. Interestingly, fibronectin (FN) was one adhesion protein that facilitated VIC adhesion and proliferation. Yet VICs did not spread on surfaces modified with RGD, a ubiquitous cell-adhesive peptide, nor with other FN-specific peptide sequences such as EILDV and PHSRN. Hyaluronic acid (HA) is a highly elastic polysaccharide that is involved in natural valve morphogenesis and possesses binding interactions with FN. Hyaluronic acid was modified to form photopolymerizable hydrogels, and VICs were found to spread and proliferate on HA-based gels, forming a confluent monolayer on the gels within 4 days. Modified HA retained its ability to specifically bind FN, allowing for the formation of gels containing both HA and FN. Valvular interstital cells cultured on HA surfaces displayed significantly increased production of extracellular matrix proteins, indicating that HA-based scaffolds may provide useful biological cues to stimulate heart valve tissue formation.


Translucent Tissue Defects in Solanum tuberosum L: I. Alterations in Amyloplast Membrane Integrity, Enzyme Activities, Sugars, and Starch Content.
Kennebec (cv) potatoes randomly developed translucent areas in their centrally located pith-parenchymal cells during storage. These defective areas were characterized as having reduced starch concentration and increased levels of free sugars (i. e. sucrose and glucose) and inorganic phosphate. Electron micrographs of potato tubers stored at 10 degrees +/- 1 degrees C for 8 months indicated that the amyloplast membrane was still intact and continuous around starch granules in both normal and prematurely sweetened tissue. The total activities of phosphorylase and sucrose-6-P synthase were elevated 5.4- and 3.8-fold, respectively, in the defective tissue compared to healthy nonsweetened tubers while there were no significant differences in the levels of sucrose synthase, UDPglucose pyrophosphorylase, invertase, or alpha-amylase. Total and specific activities of acid phosphatase were only slightly elevated in translucent tissue but their increase was significant (P < 0.05, t test) over that seen in healthy tubers. The premature sweetening in storage may have been indirectly triggered by moisture and heat stress experienced during development. Translucency eventually led to physical deterioration of the tissue.


Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents.
Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric illness in children and adolescents. Several stimulant medications, such as methylphenidate and amphetamine derivatives, are available to treat ADHD in pediatric patients. Nonstimulant medications are more preferred by some parents, other caregivers, and patients because they lack the abuse potential of stimulant medications. In the US, one available nonstimulant option is guanfacine extended release (XR). As a selective α2A adrenergic receptor, guanfacine acts on the central noradrenergic pathways and cortical noradrenergic targets to improve working memory and attention. The XR formulation of guanfacine, compared with the immediate-release formulation, is more effective for the long-term management of ADHD and is associated with fewer adverse effects. Available data also indicate that guanfacine XR is superior to atomoxetine and is as effective as the nonselective α2 adrenergic receptor agonist, clonidine XR. The most common adverse effects associated with guanfacine XR are somnolence, fatigue, bradycardia, and hypotension. Somnolence is the most often cited reason for discontinuation. Guanfacine XR is also labeled for use as an adjuvant to stimulant treatment for ADHD. A similar profile of adverse effects as reported with monotherapy is reported when guanfacine XR is "added on" to stimulant therapy with somnolence as the most commonly reported adverse event. This review discusses the clinical efficacy and patient preference of guanfacine XR based on available published data on the safety, relative effectiveness, and tolerance of this medication to treat ADHD.


Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia.
Microglia, the resident macrophage of the brain, mediates immune and inflammatory responses in the central nervous system (CNS). Activation of microglia and secretion of inflammatory cytokines associate with the pathogenesis of CNS diseases, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, prion disease, and AIDS dementia. Microbial pathogens, cytokines, chemokines, and costimulatory molecules are potent inducers of microglial activation in the CNS. Signaling through its receptor, IL-3 induces the activation of JAK-STAT and MAP kinase pathways in microglial cells. In this study, we found that in vitro treatment of EOC-20 microglial cells with tyrphostin AG490 blocked IL-3-induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B signaling proteins. Stable transfection of EOC-20 cells with a dominant negative JAK2 mutant also blocked IL-3-induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B in microglia. The blockade of JAK2-STAT5 pathway resulted in a decrease in IL-3-induced proliferation and expression of CD40 and major histocompatibility complex class II molecules in microglia. These findings highlight the fact that JAK2-STAT5 signaling pathway plays a critical role in mediating IL-3-induced activation of microglia.


In vitro assessment of solvent evaporation from commercial adhesive systems compared to experimental systems.
Solvents should be properly evaporated after application to dental substrates. The aim of this study was to assess the evaporation of commercial, experimental and neat solvents. The tested null hypotheses were that there are no differences in solvent evaporation regardless of its formulation and over time. Evaporation from commercial adhesive systems (Scotchbond Multipurpose Primer, Scotchbond Multipurpose Adhesive, Prime & Bond NT, Multi Bond, Excite, Single Bond 2, Adhese Primer, Adhese Bond, Xeno III A and Xeno III B) and experimental primers (35% HEMA plus 65% acetone or ethanol or water v/v) were compared to neat solvents (acetone, ethanol and water). Samples (10 microL) of these products were dripped into glass containers placed on a digital precision balance. Evaporation was assessed at 0, 5, 10, 15, 30, 60, 120, 300 and 600 s times to calculate mass loss. Data were analyzed statistically by ANOVA and Bonferroni's correction (a=0.05). Acetone-based products exhibited a remarkable capacity to evaporate spontaneously over time. Neat acetone evaporated significantly more than the HEMA-mixtures and the commercial formulations (p<0.05). The incorporation of monomers and other ingredients in the commercial formulations seem to reduce the evaporation capacity. Solvent evaporation was time and material-dependent.


Diagnosis and implications in the therapeutic management of patient with afebrile neurolepctic malignant syndrome.
This report aims at raising clinical awareness for the diagnosis of atypical presentations of neuroleptic malignant syndrome (NMS). We describe the case of a female patient with NMS symptoms, except fever, after starting the use of chlorpromazine. The afebrile condition delayed the consideration of NMS by the emergency clinicians who provided her initial assessment. Before this consideration, an anticholinergic agent, not recommended at this condition, was inadvertently prescribed. This might have contributed to the worsening of symptoms. NMS is a life-threatening idiosyncratic reaction most often seen as complication of antipsychotic treatment. Its clinical spectrum is broad and its diagnosis should be considered even if the patients do not fulfill all the possible described symptoms.


Hyperfractionated high-dose proton beam radiotherapy for clival chordomas after surgical removal.
To evaluate the hyperfractionated high-dose proton beam therapy (PBT) for patients with clival chordomas. Records for 19 patients with pathologically verified clival chordomas treated with surgery followed by hyperfractionated PBT were retrospectively reviewed. The first 9 consecutive patients were treated with 77.44 cobalt gray equivalents (CGEs) in 64 fractions, and the latter 10 patients were treated with 78.4 CGE in 56 fractions. The median follow-up period of all 19 cases was 61.7 months with a range from 31.5 to 115.4 months. At 5 years, the local control, cause-specific and overall survival rates for all 19 cases were 75%, 94% and 83.2%, respectively. Whereas the 5-year local control, cause-specific and over all survival rates of the latter 10 cases were 100%, 100% and 88.9%, respectively, with a median follow-up period of 59.5 months. One of the first nine patients demonstrated bilateral temporal lobe radiation necrosis, who were successfully treated conservatively. In the latter cohort, two cases showed transient neurological symptoms probably due to brain stem ischaemia, but both cases recovered completely with conservative treatment. The hyperfractionated high-dose scheme combined with maximum surgical removal was shown to be efficient for patients with clival chordomas. High-dose proton beam radiotherapy using a hyperfractionation scheme yielded a more favourable outcome than previous reports.


Factors associated with self-reported halitosis in Kuwaiti patients.
Oral malodor is a common complaint of dental patients, yet limited data is available on the actual prevalence of this condition. The aim of this study was to assess the prevalence and factors associated with self-reported halitosis in Kuwaiti patients. This was a cross-sectional study of Kuwaiti adults using a 19-point self-administered structured questionnaire on self-perception of halitosis. Significant associations between self-reported oral malodor and sociodemographic, medical history, and oral hygiene variables were examined with multiple logistic regression analysis. A total of 1551 subjects participated (response rate=86.2%). The prevalence of self-reported halitosis was 23.3%. Use of the toothbrush less than once daily was the factor most strongly associated with self-perceived halitosis (OR=2.68; 95% CI=1.83-3.92; p<0.001). Other factors significantly associated with self-perceived halitosis included current or past smoking (OR=2.51), female gender (OR=1.54), being 30 years of age or older (OR=1.35), having high school education or less (OR=1.41), history of chronic sinusitis (OR=1.58) or gastrointestinal disorders (OR=1.73), never using miswak (OR=1.56), and never using dental floss (OR=1.33). Inadequate oral hygiene practices were the factors most strongly associated with self-reported oral malodor in this sample of Kuwaiti patients. Other factors with significant associations included history of gastrointestinal tract disorders, chronic sinusitis, older age, female gender, and lower education levels.


Evolution of Nitrogen Oxide(s) during In Vivo Nitrate Reductase Assay of Soybean Leaves.
Studies were conducted to quantitate the evolution of nitrogen oxides (NO((x))) from soybean [Glycine max (L.) Merr.] leaves during in vivo nitrate reductase (NR) assays with aerobic and anaerobic gas purging. Anaerobic gas purging (N(2) and argon) consistently resulted in greater NO((x)) evolution than did aerobic gas purging (air and O(2)). The evolution of NO((x)) was dependent on gas flow rate and on NO(2) (-) formation in the assay medium; although a threshold level of NO(2) (-) appeared to exist beyond which the rate of NO((x)) evolution did not increase further.The loss of NO((x)) from in vivo NR assays under gas purging explains partially, but not stoichiometrically, the decrease in NO(2) (-) accumulation in in vivo NR assay medium with young soybean leaves. The lack of stoichiometry between NO((x)) evolution and apparent NO(2) (-) loss suggests that other mechanisms are also involved in loss of NO(2) (-) or inhibition of formation of NO(2) (-) during anaerobic and aerobic incubation conditions imposed on the in vivo NR assay of soybean. The mechanism of NO((x)) evolution under the assay conditions imposed and the relevance of this phenomenon to intact plants remains unclear.


Vesical calculus formation on non-absorbable sutures used for open inguinal hernia repair.
Iatrogenic injuries to the urogenital tract are rare, with the bladder being the organ most affected. We describe a case of a vesical calculus that formed on non-absorbable sutures that were used to repair an inguinal hernia. A 45-year-old male presented with frank haematuria and dysuria 2 years following an open left inguinal hernia repair. A CT urography showed a vesical calculus adherent to the left anterio-lateral wall of the bladder. Cystoscopy revealed that the calculus formed on non-absorbable sutures. Cystolapaxy was performed followed by cystoscopic excision of the sutures. The patient's post-operative course was uneventful. Foreign bodies in the urinary bladder always act as a nidus for formation of a calculus. Iatrogenic bladder injuries are common during hernia repair. It is however rare for sutures used to repair an inguinal hernia to involve the urinary bladder wall. The patient most likely had a full bladder at the time of hernia repair or the bladder was part of the contents of the hernia sac. This case illustrates the need to ensure that the bladder is empty prior to pelvic surgery and for surgeons to have a good understanding of inguinal anatomy to avoid injuring the contents of the hernia sac.


Clinical and pathological characteristics of brain metastasis resected after failed radiosurgery.
This study evaluates the tumor histopathology and clinical characteristics of patients who underwent resection of their brain metastasis after failed gamma knife radiosurgery. This study was a retrospective review from a prospective database. A total of 1200 brain metastases in 912 patients were treated by gamma knife radiosurgery during a 7-year period. Fifteen patients (1.6% of patients, 1.2% of all brain metastases) underwent resective surgery for either presumed tumor progression (6 patients) or worsening neurological symptoms associated with increased mass effect (9 patients). Radiographic imaging, radiosurgical and surgical treatment parameters, histopathological findings, and long-term outcomes were reviewed for all patients. The mean age at the time of radiosurgery was 57 years (age range, 32-65 years). Initial pathological diagnoses included metastatic non-small cell lung carcinoma in 8 patients (53%), melanoma in 4 patients (27%), renal cell carcinoma in 2 patients (13%), and squamous cell carcinoma of the tongue in 1 patient (7%). The mean time interval between radiosurgery and surgical extirpation was 8.5 months (range, 3 weeks to 34 months). The mean treatment volume for the resected lesion at the time of radiosurgery was 4.4 cm(3) (range, 0.6-8.4 cm(3)). The mean dose to the tumor margin was 21Gy (range, 18-24 Gy). In addition to the 15 tumors that were eventually resected, a total of 32 other metastases were treated synchronously, with a 78% control rate. The mean volume immediately before surgery for the 15 resected lesions was 7.5 cm(3) (range, 3.8-10.2 cm(3)). Histological findings after radiosurgery varied from case to case and included viable tumor, necrotic tumor, vascular hyalinization, hemosiderin-laden macrophages, reactive gliosis in surrounding brain tissue, and an elevated MIB-1 proliferation index in cases with viable tumor. The mean survival for patients in whom viable tumor was identified (9.4 months) was significantly lower than that of patients in whom only necrosis was seen (15.1 months; Fisher's exact test, P < 0.05). Radiation necrosis and tumor radioresistance are the most common causes precipitating a need for surgical resection after radiosurgery in patients with brain metastasis.


Cost analysis. Bedside blood glucose testing.
Cost analysis of the bedside blood glucose testing program at a Veterans Affairs medical center indicated a per-test cost of $11.50, as opposed to the conventional laboratory testing cost for serum glucose of $3.19. Extrapolated to the 172 Veterans Affairs hospitals, the extra cost of the procedure is estimated to be in excess of $3 million each year.


Scabies mite peritrophins are potential targets of human host innate immunity.
Pruritic scabies lesions caused by Sarcoptes scabiei burrowing in the stratum corneum of human skin facilitate opportunistic bacterial infections. Emerging resistance to current therapeutics emphasizes the need to identify novel targets for protective intervention. We have characterized several protein families located in the mite gut as crucial factors for host-parasite interactions. Among these multiple proteins inhibit human complement, presumably to avoid complement-mediated damage of gut epithelial cells. Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement. A novel full length scabies mite peritrophin (SsPTP1) was identified in a cDNA library from scabies mites. The amino acid sequence revealed four putative chitin binding domains (CBD). Recombinant expression of one CBD of the highly repetitive SsPTP1 sequence as TSP-hexaHis-fusion protein resulted in soluble protein, which demonstrated chitin binding activity in affinity chromatography assays. Antibodies against a recombinant SsPTP1 fragment were used to immunohistochemically localize native SsPTP1 in the mite gut and in fecal pellets within the upper epidermis, co-localizing with serum components such as host IgG and complement. Enzymatic deglycosylation confirmed strong N- and O-glycosylation of the native peritrophin. Serum incubation followed by immunoblotting with a monoclonal antibody against mannan binding lectin (MBL), the recognition molecule of the lectin pathway of human complement activation, indicated that MBL may specifically bind to glycosylated SsPTP1. This study adds a new aspect to the accumulating evidence that complement plays a major role in scabies mite biology. It identifies a novel peritrophin localized in the mite gut as a potential target of the lectin pathway of the complement cascade. These initial findings indicate a novel role of scabies mite peritrophins in triggering a host innate immune response within the mite gut.


Effect of early short-term cardiac rehabilitation after acute ST-elevation and non-ST-elevation myocardial infarction on 1-year mortality.
The aim was to evaluate the effect of short-term cardiac rehabilitation (CR) on clinical events during a 1-year follow-up after acute myocardial infarction. From the observational, prospective Acute COronary Syndromes (ACOS) registry, 4547 consecutive patients after ST-elevation (STEMI: n = 2432) or non-ST-elevation myocardial infarction (NSTEMI: n = 2115), recruited between June 2000 and December 2002, were characterised and evaluated for clinical outcomes during a 1-year follow-up. From the STEMI group 67.8% and from the NSTEMI group 52.3% participated in cardiac rehabilitation (CR+). Age > 70 years and previous myocardial infarction were independent predictors not to attend CR in STEMI and NSTEMI patients, whereas early revascularisation (<48 hours after hospital admission) was associated with increased likelihood to undergo CR. Multivariable analysis adjusting for propensity score shows that CR+ was independently associated with a significant reduction of all-cause mortality (STEMI: OR 0.41, 95% CI 0.28-0.60; NSTEMI: OR 0.53, 95% CI 0.38-0.76) and major adverse cardiac and cerebrovascular events (MACCE; STEMI: OR 0.66, 95% CI 0.49-0.89; NSTEMI: OR 0.73, 95% CI 0.55-0.98) during a 1-year follow-up. The study shows an independent and strong association of CR+ with markedly reduced total mortality and MACCE during a 1-year follow-up after STEMI or NSTEMI. The limitation of the study is that it is not a prospective randomised trial. Furthermore, unequal distribution of risk factors relevant for long-term prognosis had to be corrected by multivariable analysis adjusting for propensity score.