Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats.
The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min(-1) vs. 0.07 ± 0.02 min(-1), p = 0.661 for K(trans); 0.30 ± 0.05 min(-1) vs. 0.37 ± 0.11 min(-1), p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.


Aspiration of metallic mercury. A 22-year follow-up.
Rupture of the mercury-filled bag of an intestinal tube resulted in aspiration of metallic mercury 22 years ago in the patient reported. Immediate respiratory distress was treated with vigorous suctioning and postural drainage. Follow-up chest roentgenograms persistently showed radiopaque particles in the lungs. Signs and symptoms of chronic respiratory disease have since developed in the patient. Postmortem findings from the lungs included globules of metallic mercury surrounded by extensive fibrosis and granuloma formation, which we believe to be the result of local irritative effects of mercury.


Enhanced 2-deoxy-D-glucose uptake and metabolism in splenocytes from diabetic and diabetes-prone BB rats. Further evidence to support prior in vivo activation.
Glucose metabolism in splenocytes from the BB rat was studied for the presence of abnormalities in [14C] 2-deoxy-D-glucose (2-dGlc) uptake, [U-14C]glucose conversion to 14CO2, and the production of lactate and pyruvate. Cells were studied freshly isolated ("resting"), and following culture both unstimulated (control) and stimulated with concanavalin A (ConA) or phorbol myristate acetate (PMA) + ionomycin. Both resting and control cells from diabetic (BBd) and diabetes-prone (BBdp) rats transported more (p less than 0.05) 2-dGlc than did cells from nondiabetes-prone (BBn) rats. Consistent with prior in vivo activation, sustained in vitro, lactate production was higher (p less than 0.05) under control conditions in BBd and BBdp than in BBn cells. Lactate production increased less with ConA and PMA + ionomycin in both BBd and BBdp than in BBn cells. PMA + ionomycin increased 2-dGlc uptake as much in BBd and BBdp cells as in BBn cells. Elevated rates of pyruvate production were observed in BBd cells under resting, control, and (especially) ConA conditions, suggesting an abnormality in pyruvate conversion to lactate. Few changes were observed in 14CO2 production. The presence of similar abnormalities in BBdp cells to those of the BBd cells suggests that the diabetic state is not causal, and the absence of an in vitro effect of 15 mmol/liter glucose in BBn cells further tends to exclude hyperglycemia as a cause of these alterations.


Beneficial effects of consumption of acerola, cashew or guava processing by-products on intestinal health and lipid metabolism in dyslipidaemic female Wistar rats.
This study assessed the effects of diet supplementation with industrial processing by-products of acerola (Malpighia emarginata D.C.), cashew (Anacardium occidentale L.) and guava (Psidium guajava L.) fruit on the intestinal health and lipid metabolism of female Wistar rats with diet-induced dyslipidaemia. Female rats were randomly divided into five groups: healthy control, dyslipidaemic control and dyslipidaemic experimental receiving acerola, cashew or guava processing by-products. Fruit processing by-products were administered (400 mg/kg body weight) via orogastric administration for 28 consecutive days. Acerola, cashew and guava by-products caused body weight reduction (3·42, 3·08 and 5·20 %, respectively) in dyslipidaemic female rats. Dyslipidaemic female rats receiving fruit by-products, especially from acerola, presented decreased faecal pH, visceral fat, liver fat and serum lipid levels, as well as increased faecal moisture, faecal fat excretion, faecal Bifidobacterium spp. and Lactobacillus spp. counts and amounts of organic acids in faeces. Administration of the tested fruit processing by-products protected colon and liver from tissue damage (e.g. destruction of liver and colon cells and increased fat deposition in hepatocytes) induced by dyslipidaemic diet. Dietary fibres and phenolic compounds in tested fruit by-products may be associated with these positive effects. The industrial fruit processing by-products studied, mainly from acerola, exert functional properties that could enable their use to protect the harmful effects on intestinal health and lipid metabolism caused by dyslipidaemic diet.


Effects of Dietary Inorganic Nitrate Supplementation on Exercise Performance in Patients With Heart Failure: Protocol for a Randomized, Placebo-Controlled, Cross-Over Trial.
Chronic heart failure is characterized by an inability of the heart to pump enough blood to meet the demands of the body, resulting in the hallmark symptom of exercise intolerance. Chronic underperfusion of the peripheral tissues and impaired nitric oxide bioavailability have been implicated as contributors to the decrease in exercise capacity in these patients. nitric oxide bioavailability has been identified as an important mediator of exercise tolerance in healthy individuals, but there are limited studies examining the effects in patients with chronic heart failure. The proposed trial is designed to determine the effects of chronic inorganic nitrate supplementation on exercise tolerance in both patients with heart failure preserved ejection fraction (HFpEF) and heart failure reduced ejection fraction (HFrEF) and to determine whether there are any differential responses between the 2 cohorts. A secondary objective is to provide mechanistic insights into the 2 heart failure groups' exercise responses to the nitrate supplementation. Patients with chronic heart failure (15=HFpEF and 15=HFrEF) aged 40 to 85 years will be recruited. Following an initial screen cardiopulmonary exercise test, participants will be randomly allocated in a double-blind fashion to consume either a nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo (for 5 days). Participants will continue daily dosing until the completion of the 4 testing visits (maximal cardiopulmonary exercise test, submaximal exercise test with echocardiography, vascular function assessment, and vastus lateralis muscle biopsy). There will then be a 2-week washout period after which the participants will cross over to the other treatment and complete the same 4 testing visits. This study is funded by National Heart Foundation of Australia and Victoria University. Enrolment has commenced and the data collection is expected to be completed in mid 2018. The initial results are expected to be submitted for publication by the end of 2018. If inorganic nitrate supplementation can improve exercise tolerance in patients with chronic heart failure, it has the potential to aid in further refining the treatment of patients in this population. Australian New Zealand Clinical Trials Registry ACTRN12615000906550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368912 (Archived by WebCite at http://www.webcitation.org/6xymLMiFK).


QM-Cluster Model Study of the Guaiacol Hydrogen Atom Transfer and Oxygen Rebound with Cytochrome P450 Enzyme GcoA.
The key step of the O-demethylation of guaiacol by GcoA of the cytochrome P450-reductase pair was studied with DFT using two 10-residue and three 15-residue QM-cluster models. For each model, two reaction pathways were examined, beginning with a different guaiacol orientation. Based on this study, His354, Phe349, Glu249, and Pro250 residues were found to be important for keeping the heme in a planar geometry throughout the reaction. Val241 and Gly245 residues were needed in the QM-cluster models to provide the hydrophobic pocket for an appropriate guaiacol pose in the reaction. The aromatic triad Phe75, Phe169, and Phe395 may be necessary to facilitate guaiacol migrating into the enzyme active site, but it does not qualitatively affect kinetics and thermodynamics of the proposed mechanism. All QM-cluster models created by RINRUS agree very well with previous experimental work. This study provides details for better understanding enzymatic O-demethylation of lignins to form catechol derivatives by GcoA.


Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins.
The development of multidrug resistance (MDR) limits the efficacy of continuous chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers and has been associated to poor prognosis. This prompted us to investigate the involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells, the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted chemoresistance to vincristine and imatinib mesylate, followed by a decrease of Src and Bcr-Abl phosphorylation at the activating sites, inactivating both kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to chemoresistance to vincristine. Our findings describe, for the first time, that LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src and Bcr-Abl kinases in more active statuses. These findings suggest that inhibition of LMW-PTP may be a useful strategy for the development of therapies for multidrug resistant CML.


Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis.
Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses. We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-α/CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry. All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells. An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.


Characterization and Comparison of the Rumen Luminal and Epithelial Microbiome Profiles Using Metagenomic Sequencing Technique.
Bacterial dysbiosis as a result of nutritional, bacterial, viral, and parasitic gastrointestinal infections can adversely affect the metabolism, productivity, and overall health of cattle. The purpose of this project was to characterize the commensal microbiota present in two locations of the rumen concomitantly in vivo with the animals undergoing habitual husbandry, as it was hypothesized that there are major differences in the commensal microbiota present in the two locations of the adult bovine major forestomach. A surgically fitted rumen cannula was used to allow ruminal lumen contents and mucosal biopsies to be collected from six crossbred yearling steers. In order to assess as much environmental and individual steer microbiota variation as possible, each animal was randomly sampled three times over a 3 week period. 16S rRNA sequencing was performed to provide a detailed descriptive analysis from phylum to genus taxonomic level. Significant differences were observed between luminal and epimural bacterial populations in the bovine rumen. As expected, a core microbiome composed by Firmicutes and Bacteroidetes represented over 90% of the microbiome, however, further analysis showed distinct diversity and distribution of the microbiome between the two locations. Characterizing the gastrointestinal microbiome in vivo is imperative. The novelty and the contribution of this study to the literature is the use of live cattle which allowed real-time sample collections and analysis of the rumen microbiome providing an understanding of what is normal in the live animal.


The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.
The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy.


Fundamental Investigation of Adsorption Behavior onto Sodium Polystyrene Sulfonate to Potassium Ions and Its Concomitant Drugs in the Digestive Tract.
To verify the interaction between sodium polystyrene sulfonate (SPS) and its concomitant drugs, we elucidated the capability of potassium ions and concomitant drugs to adsorb onto SPS and the effect of their coexistence on the amount adsorbed. We identified 14 drugs used concomitantly with SPS from 2017-2019 in our investigation, and 5 drug preparations used in the clinical setting were used for the experiments. In the artificial intestinal juice, SPS adsorbed 39.05-69.77 mEq/g of potassium ions. Amlodipine besylate and nifedipine were well-adsorbed, while azosemide and febuxostat were did not adsorb well onto SPS. Our results and the results of a previous study suggest that additives in drug preparations affect the adsorption of drugs onto SPS. The adsorption kinetics onto SPS of drugs conformed to the pseudo-second order model. However, the adsorption of amlodipine besylate completely may not be fitted to the pseudo-second order model. The amount of amlodipine besylate adsorbed under the coexistence of potassium ions decreased compared to when potassium ions were absent. The amount of nifedipine and potassium ions adsorbed remained constant, regardless of whether potassium ions were present or not. These results might be due to the differences in their mechanisms of adsorption onto SPS and to the characteristics of the drugs. In a clinical setting, SPS is used concomitantly with various oral drugs. The interaction between SPS and its other concomitant drugs need to be elucidated more to obtain enough evidence for pharmacists to propose the appropriate prescription.


Effects of Schedule I drug laws on neuroscience research and treatment innovation.
Many psychoactive drugs are used recreationally, particularly by young people. This use and its perceived dangers have led to many different classes of drugs being banned under national laws and international conventions. Indeed, the possession of cannabis, 3,4-methylenedioxy-N-methylamphetamine (MDMA; also known as ecstasy) and psychedelics is stringently regulated. An important and unfortunate outcome of the controls placed on these and other psychoactive drugs is that they make research into their mechanisms of action and potential therapeutic uses - for example, in depression and post-traumatic stress disorder - difficult and in many cases almost impossible.


Modes, phase shifts, and losses of flat-roof open resonators.
The integral Squation of a "flat-roof resonator" is solved by the Fox and Li method of iteration in a number of particular cases. Mode patterns, phase shifts, and power losses are derived. A good overall agreement is found with the approximate theory previously developed by Toraldo di Francia. Some experimental tests carried out on a microwave model give a further confirmation of the theoretical predictions.


Rumen methanogenic genotypes differ in abundance according to host residual feed intake phenotype and diet type.
Methane is an undesirable end product of rumen fermentative activity because of associated environmental impacts and reduced host feed efficiency. Our study characterized the rumen microbial methanogenic community in beef cattle divergently selected for phenotypic residual feed intake (RFI) while offered a high-forage (HF) diet followed by a low-forage (LF) diet. Rumen fluid was collected from 14 high-RFI (HRFI) and 14 low-RFI (LRFI) animals at the end of both dietary periods. 16S rRNA gene clone libraries were used, and methanogen-specific tag-encoded pyrosequencing was carried out on the samples. We found that Methanobrevibacter spp. are the dominant methanogens in the rumen, with Methanobrevibacter smithii being the most abundant species. Differences in the abundance of Methanobrevibacter smithii and Methanosphaera stadtmanae genotypes were detected in the rumen of animals offered the LF compared to the HF diet while the abundance of Methanobrevibacter smithii genotypes was different between HRFI and LRFI animals irrespective of diet. Our results demonstrate that while a core group of methanogen operational taxonomic units (OTUs) exist across diet and phenotype, significant differences were observed in the distribution of genotypes within those OTUs. These changes in genotype abundance may contribute to the observed differences in methane emissions between efficient and inefficient animals.


Impact of a partial smoke-free legislation on myocardial infarction incidence, mortality and case-fatality in a population-based registry: the REGICOR Study.
Coronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain. Using a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA). In the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition. The 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.


Study of special-care baby services in North-west Thames region.
During three months in 1975 admissions to 17 of the 21 special-care baby units in the North-west Thames region were analysed by birth weight and category of care. Of the 1,718 babies admitted, one-third needed only observation. Neonatal intensive care formed only a small proportion of the work load in most units. Considerable variation in the pattern of admissions was found. There was some evidence of concentration, about 100 babies being transferred for urgent medical or surgical reasons, and the work load of one unit suggested that it was serving as a referral centre. It is concluded that the quality of care given to some infants needing intensive care might be improved by greater concentration, and that some units should review their admission policies in order to prevent unnecessary postpartum separation of mother and baby.


Attitudes towards health and physical activity in the elderly. Effects of a physical training program.
Attitudes towards physical activity, perceived health, body image, anxiety and life satisfaction have been studied in men and women 60 years of age and older, volunteering for progressive endurance training. Relative to other studies of younger volunteers, the senior citizens placed more value upon activity as "an esthetic experience" and as "a means to health and fitness" showing less interest in "the pursuit of vertigo." Many non-participants and "drop-outs" perceived their current fitness as satisfactory. Subjects who selected a low frequency and low intensity of training were obese, with high Cornell Medical Index (CMI) scores on both organic and psychological scales. After 14 weeks of conditioning, 83% of subjects reported improvements in well-being. However, CMI scores were reduced on only one of twelve organic scales and none of the behavior, mood and feeling scales. Neugarten's Life Satisfaction Index, Kenyon's Body Image scales, and McPherson's the Real Me scores remained unchanged, but there was a decrease of Manifest Anxiety (Taylor scale) and a greater regard of physical activity as "the relief of tension." When subjects were classed according to changes in aerobic power, between group differences were found for "Real Me" scores and for three of Kenyon's attitude scales. Persons who trained frequently and intensively showed improvements for body image and for five of Kenyon's attitude scales.


Post percutaneous coronary intervention hemoglobin levels predict in-hospital mortality in patients with STEMI treated with primary percutaneous coronary intervention.
In this study, we aimed to determine whether admission hemoglobin versus post-percutaneous coronary intervention (PCI) hemoglobin level at 24 hours is a predictor of in-hospital mortality for patients with ST elevation myocardial infarction (STEMI) without evidence of clinical hemorrhage who underwent primary PCI. In this study, we included 1,444 consecutive patients with STEMI who underwent primary PCI at a tertiary heart hospital. The primary outcome of the study was the in-hospital all-cause mortality. We used the penalized maximum likelihood estimation (PMLE) logistic regression method to examine the relationship between primary outcome and candidate predictors. In total, 172 (11.9%) patients died during the in-hospital course. According to a PMLE logistic regression analysis, age, KILLIP class ≥2, pre-PCI thrombolysis in myocardial infarction (TIMI) flow <3, systolic blood pressure, creatinine, glycoprotein IIb/IIIa inhibitor use, and post-PCI hemoglobin levels at 24 hours were predictors of in-hospital mortality. The relative importance of post-PCI hemoglobin at 24 hours (contributing 6% of the explainable outcome in the model) was significantly higher than admission hemoglobin (contributing only 0.1% of the explainable outcome in the model). This study demonstrated that post-PCI hemoglobin levels were independently associated with in-hospital survival in patients with STEMI without evidence of bleeding following primary PCI. In addition, post-PCI hemoglobin was a better predictor of in-hospital mortality than admission hemoglobin for patients with STEMI who underwent primary PCI.


Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome.
L-carnitine (L-C), a ubiquitous nutritional supplement, has been investigated as a potential therapy for cardiovascular disease, but its effects on human atherosclerosis are unknown. Clinical studies suggest improvement of some cardiovascular risk factors, whereas others show increased plasma levels of pro-atherogenic trimethylamine N-oxide. The primary aim was to determine whether L-C therapy led to progression or regression of carotid total plaque volume (TPV) in participants with metabolic syndrome (MetS). This was a phase 2, prospective, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined as ≥ 3/5 cardiac risk factors: elevated waist circumference; elevated triglycerides; reduced HDL-cholesterol; elevated blood pressure; elevated glucose or HbA1c; or on treatment. Participants with a baseline TPV ≥ 50 mm3 were randomized to placebo or 2 g L-C daily for 6 months. The primary outcome was the percent change in TPV over 6 months. In 157 participants (L-C N = 76, placebo N = 81), no difference in TPV change between arms was found. The L-C group had a greater increase in carotid atherosclerotic stenosis of 9.3% (p = 0.02) than the placebo group. There was a greater increase in total cholesterol and LDL-C levels in the L-C arm. Though total carotid plaque volume did not change in MetS participants taking L-C over 6-months, there was a concerning progression of carotid plaque stenosis. The potential harm of L-C in MetS and its association with pro-atherogenic metabolites raises concerns for its further use as a potential therapy and its widespread availability as a nutritional supplement. ClinicalTrials.gov, NCT02117661, Registered April 21, 2014, https://clinicaltrials.gov/ct2/show/NCT02117661 .


[Intensive insulin therapy in adolescents with type 1 diabetes mellitus: initial experiences with a semiautomatic insulin injection device (the insulin pen)].
Recently new pen-like technical devices (Insulin-Pen) for the administration of insulin have become available. With the new device, short acting insulin is injected before meals and, in addition, a long acting insulin before bedtime (basis-bolus insulin regime). A group of 19 adolescents with type I diabetes mellitus (7 girls, 12 boys, age 12-18 years) have been trained during a short hospital stay (4-5 days with intensive teaching) in the new insulin regime. Experience, now amounting to 131 patients-months, has been favourable without exception. Acceptance is good, and none of the adolescents would prefer to go back to the conventional insulin regime with two injections. Regained flexibility with the amount and timing of meals, and the possibility of reducing the number of meals, have been mentioned as the principal advantages of the new system. The intensified self-monitoring of blood glucose usually was the most cited disadvantage. However, several adolescents felt more assured in daily life with a knowledge of blood glucose levels. Compliance in the management of diabetes during puberty increased markedly; as a result, longterm metabolic control improved significantly. The glycosylated hemoglobin A1 was 9.9 +/- 0.8% before and 7.7 +/- 0.5% (normal less than 8%) with the new insulin regime (p less than 0.001). It is concluded that the use of new pen-like insulin injectors helps to improve metabolic control as well as life quality in insulin-dependent adolescent diabetics. However, of equal importance is instruction by the diabetologist with respect to new possibilities and limitations, particularly the new rules of diet.


[Biological adaptation and immune status of preschool children with visual function disorders in conditions of preschool educational institutions of compensating type].
For implementation of a comprehensive approach in the elaboration of preventive and corrective measures in children with impaired visual function in conditions of preschool educational institutions of compensating type there were studied adaptation reserves of their organism, as well as indices of immune status. Biological adaptation was studied with the help ofcardiointervalography in 111 children aged 6-7years. With the use of ELISA 88 children were examined in terms of IgA, IgM, IgG, slgA in saliva.


Recent developments in nanofabrication using focused ion beams.
Focused ion beam (FIB) technology has become increasingly popular in the fabrication of nanoscale structures. In this paper, the recent developments of the FIB technology are examined with emphasis on its ability to fabricate a wide variety of nanostructures. FIB-based nanofabrication involves four major approaches: milling, implantation, ion-induced deposition, and ion-assisted etching of materials; all these approaches are reviewed separately. Following an introduction of the uniqueness and strength of the technology, the ion source and systems used for FIB are presented. The principle and specific techniques underlying each of the four approaches are subsequently studied with emphasis on their abilities of writing structures with nanoscale accuracy. The differences and uniqueness among these techniques are also discussed. Finally, concluding remarks are provided where the strength and weakness of the techniques studied are summarized and the scopes for technological improvement and future research are recommended.


The power of word-frequency-based alignment-free functions: a comprehensive large-scale experimental analysis.
Alignment-free (AF) distance/similarity functions are a key tool for sequence analysis. Experimental studies on real datasets abound and, to some extent, there are also studies regarding their control of false positive rate (Type I error). However, assessment of their power, i.e. their ability to identify true similarity, has been limited to some members of the D2 family. The corresponding experimental studies have concentrated on short sequences, a scenario no longer adequate for current applications, where sequence lengths may vary considerably. Such a State of the Art is methodologically problematic, since information regarding a key feature such as power is either missing or limited. By concentrating on a representative set of word-frequency-based AF functions, we perform the first coherent and uniform evaluation of the power, involving also Type I error for completeness. Two alternative models of important genomic features (CIS Regulatory Modules and Horizontal Gene Transfer), a wide range of sequence lengths from a few thousand to millions, and different values of k have been used. As a result, we provide a characterization of those AF functions that is novel and informative. Indeed, we identify weak and strong points of each function considered, which may be used as a guide to choose one for analysis tasks. Remarkably, of the 15 functions that we have considered, only four stand out, with small differences between small and short sequence length scenarios. Finally, to encourage the use of our methodology for validation of future AF functions, the Big Data platform supporting it is public. The software is available at: https://github.com/pipp8/power_statistics. Supplementary data are available at Bioinformatics online.


The accessory middle cerebral artery as a collateral blood supply.
We describe two cases of acute embolic occlusion of the internal carotid artery and the middle cerebral artery in association with a patent accessory middle cerebral artery. Because of the presence of the accessory middle cerebral artery, the frontal lobe was salvaged to some extent, but it did not provide sufficient collateral blood supply to the middle cerebral artery territory to spare the rest of the frontal lobe, the temporal lobe, and the basal ganglia.


Group A streptococcus polysaccharide: studies on its preparation, chemical composition, and cellular localization after intravenous injection into mice.
A method was developed for the extraction of the group A streptococcus polysaccharide employing pepsin digestion of ground streptococcal cells. This method did not result in the isolation of polysaccharide with chemical and physical chemical properties different from those exhibited by preparations extracted with hot formamide. Studies of the chemical composition of this polysaccharide demonstrated it to be composed chiefly of rhamnose and glucosamine monosaccharide units in the approximate ratio of five moles of rhamnose to two moles of glucosamine. The fate of the polysaccharide after intravenous injection into mice was studied using the fluorescent antibody technique. It was found to be rapidly eliminated by the kidney. The presence of the polysaccharide in the renal tubular epithelial cells during the excretory phase was the only evidence of its cellular localization that could be detected under the conditions of these experiments.


[Hypertension and left ventricular hypertrophy in patients with spontaneous subarachnoid hemorrhage].
One hundred and eighteen consecutive cases of spontaneous subarachnoid haemorrhage seen at one hospital during a three-year period were examined to assess the prevalence of hypertension and the correlation between the presence of hypertension and the risk of early death. Eighty-seven of the patients had intracranial aneurysms. The diagnosis of hypertension was determined by means of three complementary criteria: a history of treatment with antihypertensive drugs; systolic and/or diastolic blood pressure levels > or = 160 and 95 mmHg, respectively, measured by the general practitioners of the patients before the onset of the subarachnoid haemorrhage; and the presence of left ventricular hypertrophy determined by echocardiography and/or necropsy. The major findings were as follows: 1) hypertension was present in at least 41% of the patients; 2) in 37% of 51 patients with no history of hypertension before the haemorrhage, left ventricular hypertrophy was diagnosed; and 3) the frequency of hypertension was significantly higher in patients who died within 14 days after the bleeding episode compared with patients surviving this period.


Direct characterization of iodine covalently bound to fulvic acids by electrospray mass spectrometry.
Numerous studies have demonstrated that humic substances (HS) react with iodine to form iodo derivatives and thereby can control the bioavailability of radioisotopes. Unfortunately, none of these studies have provided detailed insights into product compounds and so far, to our knowledge, the direct analysis of these species by electrospray ionization (ESI) mass spectrometry has not been explored. The reactivity of iodine with fulvic acids (FA) present in HS was investigated by means of ESI coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer. ESI spectra of solutions, that were indicated by MS/MS analysis to have formed iodinated species, apparently displayed singly charged ions corresponding in m/z to hypothesized species, viz., [RI - H](-), R = (substituted FA compound). MS/MS analysis based on the diagnostic fragment ions for FA compounds and their iodo derivatives suggests that FA undergo aromatic substitutions. Furthermore, significant differences in mass profiles are observed that presumably result from extended redox reactions. The ESI-MS technique opens up new opportunities to understand the scavenging properties of HS towards radionuclides and heavy metals for environmental studies.


The efficacy of the immunoperoxidase technique for the detection of several antigens after destaining of stored stained sections.
1. Sections previously stained with hematoxylin-eosin and periodic acid-Schiff were destained and subjected to the peroxidase-antiperoxidase (PAP) technique for the identification of the following antigens: hepatitis B surface antigen, hepatitis B core antigen, alpha-1-antitrypsin, alpha-fetoprotein, immunoglobulin G and immunoglobulin M. 2. The results obtained after destaining of previously stained sections were similar to those obtained with material that had not been stained, indicating that the sensitivity and specificity of the immunological reaction had not been affected by the previous treatments. 3. The results reported here extend the number of antigens that can be detected by the PAP technique after destaining of sections stained by traditional histochemical methods and consequently increase the opportunity for retrospective studies.


Global exponential convergence of Cohen-Grossberg neural networks with time delays.
In this paper, we derive a general sufficient condition ensuring global exponential convergence of Cohen-Grossberg neural networks with time delays by constructing a novel Lyapunov functional and smartly estimating its derivative. The proposed condition is related to the convex combinations of the column-sum and the row-sum of the connection matrices and also relaxes the constraints on the network coefficients. Therefore, the proposed condition generalizes some previous results in the literature.


Screening Strategy of Active Pulmonary Tuberculosis in Sheltered Homeless People in Marseille, 2019.
We aimed to assess the reliability of a screening questionnaire for Active Pulmonary Tuberculosis (APTB) in a population of sheltered homeless persons (HP). Participants from two homeless shelters completed a questionnaire specially designed to identify patients at high-risk of APTB (available at www.tb-screen.ch), underwent a Chest X-ray (CXR), and provided sputum samples. Computed Tomography (CT) scanning was subsequently performed on those which had images consistent with APTB. Microscopical examination, real-time polymerase chain reaction (qPCR) and culture testing were applied for Mycobacterium tuberculosis complex detection. Additionally, we retrospectively selected 16 HP hospitalised in our hospital between 2017 and 2019 with biologically confirmed tuberculosis and typical CXR images, and retrospectively documented a screening questionnaire by reviewing their medical files. Overall, the population (n = 383 HP) was predominantly migrants (87%). Forty-seven individuals (11.7%) had positive screening questionnaire scores and four (2.4%) displayed abnormal CXR features consistent with APTB. Three of them three underwent CT scanning that ruled out APTB and one was lost to follow-up. None tested positive through microbiological investigation. Fifteen (of 16, 93.8%) hospitalised patients with biologically confirmed APTB had a positive screening questionnaire score. The sensitivity and specificity of questionnaire for confirmed APTB were 93.8% and 87.7%, respectively. Screening questionnaires can be used as a first assessment tool in people arriving at homeless shelters and to refer those screening positive for a CXR.


Desynchronization and pattern formation in a noisy feed-forward oscillator network.
We consider a one-dimensional directional array of diffusively coupled oscillators. They are perturbed by the injection of small additive noise, typically orders of magnitude smaller than the oscillation amplitude, and the system is studied in a region of the parameters that would yield deterministic synchronization. Non-normal directed couplings seed a coherent amplification of the perturbation: this latter manifests as a modulation, transversal to the limit cycle, which gains in potency node after node. If the lattice extends long enough, the initial synchrony gets eventually lost, and the system moves toward a nontrivial attractor, which can be analytically characterized as an asymptotic splay state. The noise assisted instability, ultimately vehiculated and amplified by the non-normal nature of the imposed couplings, eventually destabilizes also this second attractor. This phenomenon yields spatiotemporal patterns, which cannot be anticipated by a conventional linear stability analysis.


The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib.
Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.


Visual responses in the lateral geniculate nucleus of dichromatic and trichromatic marmosets (Callithrix jacchus).
New-world primates such as the marmoset (Callithrix jacchus) show polymorphism for the middle- to long-wavelength sensitive cone pigments. Each X-chromosome carries a gene for only one of three possible pigments. All males are thus dichromats, but some females will be trichromats. We have investigated the responses of cells of the parvocellular (PC) and magnocellular (MC) systems within animals from a single marmoset family. The middle- to long-wavelength pigment of dichromats was identified physiologically. Trichromats could readily be distinguished from dichromats by the presence of a high proportion of red-green opponent PC-cells. The physiological classification of phenotypes was confirmed with genetic analysis. The pattern of inheritance was consistent with current genetic models. In trichromatic females, the properties of cells resembled in detail those of cells from the PC- and MC-pathways of the macaque. In dichromats, cell responses resembled those of trichromats (except for the lack of opponency in PC-cells); PC-cells showed sustained and MC-cells transient responses, with a lower contrast gain for the former type. One difference was that a proportion of PC-cells in dichromats showed strong rod input even at high levels of retinal illuminance. Thus, in trichromatic marmosets the presence of two middle- to long-wave pigments appears to permit the elaboration of all the physiological properties associated with trichromacy.


Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study: results of a secondary multistate modelling analysis.
A large randomised treatment trial (SERVE-HF) showed that treatment of central sleep apnoea with adaptive servoventilation in patients with heart failure and reduced ejection fraction (HFREF) increased mortality, although the analysis of the composite primary endpoint (time to first event of death from any cause, life-saving cardiovascular intervention, or unplanned hospital admission for worsening heart failure) was neutral. This secondary multistate modelling analysis of SERVE-HF data investigated associations between adaptive servoventilation and individual components of the primary endpoint to try to better understand the mechanisms underlying the observed increased mortality. In SERVE-HF, participants were randomly assigned to receive either optimum medical treatment for heart failure alone (control group), or in combination with adaptive servoventilation. We analysed individual components of the primary SERVE-HF endpoint separately in a multistate model, with and without three covariates suggested for effect modification (implantable cardioverter defibrillator at baseline, left ventricular ejection fraction [LVEF], and proportion of Cheyne-Stokes Respiration [CSR]). The SERVE-HF study is registered with ClinicalTrials.gov, number NCT00733343. Univariate analysis showed an increased risk of both cardiovascular death without previous hospital admission (hazard ratio [HR] 2·59, 95% CI 1·54-4·37, p<0·001) and cardiovascular death after a life-saving event (1·57, 1·01-2·44, p=0·045) in the group receiving adaptive servoventilation versus the control group. Adjusted analysis showed that the increased risk attributed to adaptive servoventilation of cardiovascular death without previous hospital admission for worsening heart failure varied with LVEF and that the risk attributed to adaptive servoventilation of hospital admission for worsening heart failure varied with LVEF and CSR. In patients with LVEF less than or equal to 30%, use of adaptive servoventilation markedly increased the risk of cardiovascular death without previous hospital admission (HR 5·21, 95% CI 2·11-12·89, p=0·026). Adaptive servoventilation is associated with an increased risk of cardiovascular death in patients with heart failure and reduced ejection fraction (LVEF ≤45%) treated for predominant central sleep apnoea. This multistate modelling analysis shows that this risk is increased for cardiovascular death in patients not previously admitted to hospital, presumably due to sudden death, and in patients with poor left ventricular function. ResMed.


Presence of presynaptic neurotoxin complexes in the venoms of Australo-Papuan death adders (Acanthophis spp.).
Australo-papuan death adders (Acanthophis spp.) are a cause of serious envenomations in Papua New Guinea and northern Australia often resulting in neurotoxic paralysis. Furthermore, victims occasionally present with delayed-onset neurotoxicity that sometimes responds poorly to antivenom or anticholinesterase treatment. This clinical outcome could be explained by the presence of potent snake presynaptic phospholipase A(2) neurotoxin (SPAN) complexes and monomers, in addition to long- and short-chain postsynaptic alpha-neurotoxins, that bind irreversibly, block neurotransmitter release and result in degeneration of the nerve terminal. The present study therefore aimed to determine within-genus variations in expression of high molecular mass SPAN complexes in the venoms of six major species of Acanthophis, four geographic variants of Acanthophis antarcticus. Venoms were separated by size-exclusion liquid chromatography under non-denaturing conditions and fractions corresponding to proteins in the range of 22 to >60 kDa were subjected to pharmacological characterization using the isolated chick biventer cervicis nerve-muscle (CBCNM) preparation. All venoms, except Acanthophis wellsi and Acanthophis pyrrhus, contained high mass fractions with phospholipase A(2) activity that inhibited twitch contractions of the CBCNM preparation. This inhibition was of slow onset, and responses to exogenous nicotinic agonists were not blocked, consistent with the presence of SPAN complexes. The results of the present study indicate that clinicians may need to be aware of possible prejunctional neurotoxicity following envenomations from A. antarcticus (all geographic variants except perhaps South Australia), Acanthophis praelongus, Acanthophis rugosus and Acanthophis. laevis species, and that early antivenom intervention is important in preventing further development of toxicity.


Does electrothrombosis occur immediately after embolization of an aneurysm with Guglielmi detachable coils?
Current options for treating cerebral aneurysms include surgical clipping and placement of Guglielmi detachable coils (GDCs). The latter system is reported to induce acute aneurysmal occlusion by a mechanism of electrothrombosis. We report our observations in the case of a ruptured aneurysm treated with GDCs and then surgically exposed 2 hours later. The lack of thrombus within the aneurysm and around the coils led us to question the mechanism of action of GDCs.


ERK activation precedes Purkinje cell loss in mice with Spinocerebellar ataxia type 17.
Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant neurodegenerative disease caused by CAG expansion in the gene encoding the TATA-binding protein (TBP). The neurological features of SCA17 are Purkinje cell loss and gliosis. We have generated SCA17 transgenic mice which recapitulate the patients' phenotypes and are suitable for the study of the SCA17 pathomechanism. Our previous study identified the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) occurred in the SCA17 cerebella, this study aims to study the role of ERK activation in SCA17. The levels of pERK, calbindin, and gliosis markers on the mouse cerebellum at 4-8 weeks old were analyzed to elucidate the correlation among behavioral performance, ERK activation and Purkinje cell degeneration. The motor incoordination was initiated in SCA17 mice at 6 weeks old. We found that the presence of TBP nuclear aggregation and microglia activation were observed at 4 weeks old. Gliosis of astrocytes and Bergmann glia, pERK, Bax/Bcl2 ratio, and caspase-3 were significantly increased in the 6-week-old SCA17 mouse cerebellum. In addition to the polyglutamine-protein aggregation in Purkinje cells caused apoptosis cell-autonomously, a significant body of evidence have shown that ERK pathways involves in neuronal apoptosis. Our study showed that the activation of ERK in the astrocytes and Bergmann glia was identified as preceding motor deficits, which suggest the elevated gliosis by ERK activation may contribute to neuronal apoptosis in SCA17 mice.


Estimating insect flight densities from attractive trap catches and flight height distributions.
Methods and equations have not been developed previously to estimate insect flight densities, a key factor in decisions regarding trap and lure deployment in programs of monitoring, mass trapping, and mating disruption with semiochemicals. An equation to estimate densities of flying insects per hectare is presented that uses the standard deviation (SD) of the vertical flight distribution, trapping time, the trap's spherical effective radius (ER), catch at the mean flight height (as estimated from a best-fitting normal distribution with SD), and an estimated average flight speed. Data from previous reports were used to estimate flight densities with the equations. The same equations can use traps with pheromone lures or attractive colors with a measured effective attraction radius (EAR) instead of the ER. In practice, EAR is more useful than ER for flight density calculations since attractive traps catch higher numbers of insects and thus can measure lower populations more readily. Computer simulations in three dimensions with varying numbers of insects (density) and varying EAR were used to validate the equations for density estimates of insects in the field. Few studies have provided data to obtain EAR, SD, speed, and trapping time to estimate flight densities per hectare. However, the necessary parameters can be measured more precisely in future studies.


Influence of drought and heat stress, applied independently or in combination during seed development, on qualitative and quantitative aspects of seeds of lentil (Lens culinaris Medikus) genotypes, differing in drought sensitivity.
Terminal droughts, along with high temperatures, are becoming more frequent to strongly influence the seed development in cool-season pulses like lentil. In the present study, the lentil plants growing outdoors under natural environment were subjected to following treatments at the time of seed filling till maturity: (a) 28/23 °C day/night temperature as controls; (b) drought stressed, plants maintained at 50% field capacity, under the same growth conditions as in a; (c) heat stressed, 33/28 °C day/night temperature, under the same growth conditions as in a; and (d) drought + heat stressed, plants at 50% field capacity, 33/28 °C day/night temperature, under the same growth conditions as in (a). Both heat and drought resulted in marked reduction in the rate and duration of seed filling to decrease the final seed size; drought resulted in more damage than heat stress; combined stresses accentuated the damage to seed starch, storage proteins and their fractions, minerals, and several amino acids. Comparison of a drought-tolerant and a drought-sensitive genotype indicated the former type showed significantly less damage to various components of seeds, under drought as well as heat stress suggesting a cross tolerance, which was linked to its (drought tolerant) better capacity to retain more water in leaves and hence more photo-assimilation ability, compared with drought-sensitive genotype.


Dysregulation of neuroendocrine crossroads: depression, circadian rhythms and the retina--a hypothesis.
The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as -gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal-hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events.


The first fifty microarray studies in filamentous fungi.
Microarray studies have examined global gene expression in over 20 species of filamentous fungi encompassing a wide variety of research areas. The majority have addressed aspects of metabolism or pathogenicity. Metabolic studies have revealed important differences in the transcriptional regulation of genes for primary metabolic pathways between filamentous fungi and yeast. Transcriptional profiles for genes involved in secondary metabolism have also been established. Genes required for the biosynthesis of both useful and detrimental secondary metabolites have been identified. Due to the economic, ecological and medical implications, it is not surprising that many studies have used microarray analysis to examine gene expression in pathogenic filamentous fungi. Genes involved in various stages of pathogenicity have been identified, including those thought to be important for adaptation to the host environment. While most of the studies have simulated pathogenic conditions in vitro, a small number have also reported fungal gene expression within their plant hosts. This review summarizes the first 50 microarray studies in filamentous fungi and highlights areas for future investigation.


Patient selection in the treatment of glabellar wrinkles with botulinum toxin type A injection.
To determine the dose-response characteristics and side-effects profile of Clostridium botulinum type A exotoxin (Botox) used to treat glabellar wrinkles and develop guidelines for patient selection based on the nature and severity of the treated wrinkles. Prospective, nonrandomized pilot and electromyogram (EMG)-guided studies. Two ambulatory care clinics at university hospitals. For the pilot study, volunteer samples of 23 patients with glabellar wrinkles; for the EMG-guided study, volunteer samples of 57 patients with glabellar wrinkles. For the pilot study, 23 patients were serially injected with up to 10.0 mouse units (MU) of Botox into each corrugator muscle; for the EMG-guided study, 57 patients were injected under EMG guidance with an initial dose of 10.0 MU of Botox into each corrugator muscle. Eleven patients with persistent corrugator activity were reinjected with 10.0 MU of Botox. For the pilot study, slide photographs were obtained before and 2 weeks after injection; for the EMG-guided study, slide photographs were obtained before and at 2 weeks and at 2 months after injection. Patients were asked to evaluate results numerically. For the pilot study, injection of up to 10.0 MU of Botox into each corrugator muscle produced a satisfactory improvement in 12 patients; for the EMG-guided study, 43 patients were satisfied with improvement after full abolition of corrugator or accessory lateral brow muscle activity. Women were more likely to achieve satisfactory results than were men (80% [40/50] vs 43% [3/7]; P < or = .03). Improvement was not age related. No significant side effects or complications were observed. Glabellar wrinkles may be satisfactorily treated with Botox injection into the corrugator supercilii muscles. Improvement is temporary, dose dependent, and may not be seen in some patients even with successful denervation of the treated muscles. Clinicians may begin treatment with a dose of 10.0 MU of Botox into each corrugator muscle, and may select candidates for injection by determining the type of wrinkle to be treated and its spreadability (glabellar spread test).


[Isolated renal mucormicosis].
Mucormycosis is an infection caused by a class Zygomycetes fungi. The rhinocerebral and pulmonary are the most common clinical presentations. Renal mucormycosis is a very rare form. To date, only 25 cases have been reported in the literature. We describe the case of a patient with leukemia who developed isolated renal mucormycosis and review the literature.


Policing the past: cold case studies, forensic evidence and retroactive social control.
In this article an empirically grounded study of the police practices used when conducting cold case reviews of unsolved homicides is used to illuminate the key features of what is termed 'retroactive social control'. It is suggested that this mode of social control, that works by placing past events under new descriptions, is an increasingly important feature of how social control is being imagined and delivered, and is predicated upon the capacity to de-stabilize and re-write previous official definitions of a situation. Retroactive social control it is posited encompasses two inter-twined dimensions: the social control of collective memory, in terms of what is remembered and how; and social control through memory, wherein the shaping of the past influences the enactment of control in the present. The focus upon police cold case reviews suggests how forensic evidence and new investigative technologies have played an important role in shaping the development of these innovative aspects of contemporary policing. As such, the empirical focus illuminates a broader trend relating to how developments in science and technology are affording new possibilities in the ways that social control is conceptualized and conducted.


Correlation of in vitro cytotoxicity with preclinical in vivo antitumor activity.
Several human and murine tumor cell lines were evaluated in an in vitro cytotoxicity assay as prescreens for fermentation extracts and pure materials subsequently tested in vivo against P388 leukemia or B16 melanoma. Each material, regardless of its in vitro cytotoxicity, was evaluated in vivo. At the criteria levels of in vitro positivity and in vivo activity invoked, a highly significant relationship between these two endpoints was demonstrated for each cell line. When cell lines were compared, most of them performed in a similar manner, with HCT-116 human colon carcinoma cells providing a modest advantage predicting for P388 activity in some comparisons. Using the data from any two cell lines in concert did not improve the acuity of the prescreen beyond that associated with the better cell lines used singularly and only a minority of active materials was predicted for uniquely. Overall, the in vitro cytotoxicity assay provided a useful prescreen for selecting P388 and B16 in vivo active materials.


Making lasting memories: remembering the significant.
Although forgetting is the common fate of most of our experiences, much evidence indicates that emotional arousal enhances the storage of memories, thus serving to create, selectively, lasting memories of our more important experiences. The neurobiological systems mediating emotional arousal and memory are very closely linked. The adrenal stress hormones epinephrine and corticosterone released by emotional arousal regulate the consolidation of long-term memory. The amygdala plays a critical role in mediating these stress hormone influences. The release of norepinephrine in the amygdala and the activation of noradrenergic receptors are essential for stress hormone-induced memory enhancement. The findings of both animal and human studies provide compelling evidence that stress-induced activation of the amygdala and its interactions with other brain regions involved in processing memory play a critical role in ensuring that emotionally significant experiences are well-remembered. Recent research has determined that some human subjects have highly superior autobiographic memory of their daily experiences and that there are structural differences in the brains of these subjects compared with the brains of subjects who do not have such memory. Understanding of neurobiological bases of such exceptional memory may provide additional insights into the processes underlying the selectivity of memory.


[Current status of the study of genital sympathetic evoked potentials in the assessment of impotence].
To determine the usefulness of penile sympathetic skin response (PSSR) in the study of impotence. The PSSR, hand sympathetic skin response (HSSR), filling videocystography and SPACE (single potential analysis cavernous electromyography) were performed in 39 patients referred for study of impotence. A relationship between not obtaining PSSR and an open bladder neck (60%) in the videocystography at filling, and between a closed bladder neck and obtained PSSR (81%) was demonstrated. The percentage of normal hand sympathetic potentials was similar for patients with obtained and not obtained PSSR. The relationship between the degree of activity of the SPACE and the type of PSSR could not be demonstrated. The determination of the PSSR allows us to evaluate the sympathetic cavernous innervation. This would obviate performing a filling videocystography in the study of the neuroandrologic profile in impotence. The information obtained by PSSR is independent of that obtained from SPACE, therefore both procedures complement each other in the neuroandrologic study of impotence.


Tattoo pigment mimics positive sentinel lymph node in melanoma.
A 42-year-old man with metastasizing melanoma from an unknown primary is presented. Initially a subcutaneous metastasis in the scapular region and a single lung metastasis were resected. Thorough examinations did not show any evidence of a primary tumour. From the site of the metastasis on the right scapular region, lymphoscintigraphy with axillary sentinel lymph node biopsy was performed. One axillary lymph node could be identified intra-operatively with the gamma probe as sentinel node. The sentinel node and 4 adjacent lymph nodes clinically showed black pigmentation. However, histopathological examination of the lymph nodes did not detect micrometastases. The pigmentation of the lymph nodes was due to decorative tattoos of the scapular skin.


[The genera of Bethylidae (Hymenoptera: Chrysidoidea) in four areas of Atlantic Rain Forest from Espírito Santo, Brazil].
The generic richness and abundance of Bethylidae collected in four different hillside areas of Atlantic rain forest from Espírito Santo, Brazil were studied. The sites are Santa Maria de Jetibá (SMJ), Domingos Martins (DM), Pancas (P) and Atílio Vivacqua (AV). A total of 2,840 specimens of 12 genera were collected. Lepidosternopsis Ogloblin and Bakeriella Kieffer are first recorded from the State. Richness of taxa was calculated using first-order Jackknife richness with EstimateS program. Genera accumulation curves were ran to evaluate the samples. Abundance data were adjusted to the geometric distribution. Parameter k was used to compare areas. The generic profile was not equal for the sites we studied. The areas were considered disturbed. SMJ and DM presented genera richness bigger than in P and AV. The differences in the sites reflect the different preservation of each environment. Pseudisobrachium Kieffer and Dissomphalus Ashmead are most dominant genera in SMJ, DM and P, and Anisepyris Kieffer in AV. This study emphasizes the fact of Dissomphalus as the most abundant genus in rain forests. The generic profile found in AV is similar to that of some areas of Brazilian savannah.


[History of healing; bath treatment as psychiatric therapy (1900-1950)].
During the first decade of the twentieth century the prolonged bath treatment was introduced as a therapy for restless patients in Dutch psychiatric institutions. They were kept for hours or days at a stretch in lukewarm water, in order to calm them down. It became a common treatment, which nevertheless was gradually replaced by occupational therapy. The rise of psychopharmacology during the fifties of this century marked the end of the prolonged bath treatment.


Cabozantinib for the treatment of kidney cancer.
Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy. Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator. Cabozantinib also showed activity in the front line setting in RCC within the CABOSUN trial. The study randomized untreated metastatic RCC patients to either cabozantinib or sunitinib and the former showed improved progression free survival which was the primary endpoint. The future holds promise for indications in other malignancies, given the preliminary efficacy and unique mechanism of action of cabozantinib. In this review we address the mechanism of action, pharmacodynamics and pharmacokinetics of cabozantinib, and also review the development pathway of this agent in the treatment of advanced renal cell carcinoma. The potential benefit in specific patient populations, such as poor risk patients and bone metastases subgroups is also discussed. Expert commentary: The clinical applications of cabozantinib will be addressed within the context of the current competitive therapeutic landscape of RCC.


Biologic Therapies for Giant Cell Arteritis.
Glucocorticoids have been the mainstay of treatment in giant cell arteritis (GCA) for the past 70 years. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) have largely failed to show significant clinical efficacy or reduction of the glucocorticoid burden in GCA. Tocilizumab is the first biologic to make a substantial impact in GCA treatment. With the current understanding of GCA pathogenesis implicating multiple cytokines, notably interleukin (IL) 6, IL-12, IL-23, IL-1β, and the role of janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) pathway in these cytokines, many biologics are currently being investigated in GCA. This review article looks at the existing evidence for biologic agents in GCA. In addition to tocilizumab, the potential role of ustekinumab, abatacept, JAK inhibitors and other promising biologics in GCA are discussed in detail. A treatment algorithm based on the best evidence to date is also presented.


CD40 ligand stimulates proinflammatory cytokine production by human endothelial cells.
Functional expression of CD40 has recently been described on the surface of HUVEC, and activation of these cells with CD40 ligand (CD40-L) leads to increased adhesion molecule expression. Here, we analyzed the effect of CD40 triggering on cytokine production by HUVEC. CD40-L-transfected fibroblasts, in contrast to their untransfected counterparts, as well as a soluble recombinant human CD40-L/murine CD8alpha chimeric molecule were able to importantly increase (by a mean of fourfold) the production of leukemia inhibitory factor (LIF) by HUVEC. CD40-L displayed an additive effect with IL-4, IL-1alpha, and TNF-alpha on the enhancement of LIF secretion. Cyclosporin A did not affect LIF synthesis by resting or CD40-L-activated HUVEC, whereas dexamethasone diminished the basal level of LIF production and abrogated the CD40-L effect. The secretions of two other proinflammatory cytokines, granulocyte-macrophage CSF and IL-6, were also increased in the presence of CD40-L. However, CD40-L neither affected HUVEC proliferation nor rescued them from IFN-gamma- and TNF-alpha induced apoptosis. Together, these results indicate that endothelial cell activation by CD40-L may play an important role not only in leukocyte recruitment through enhancement of adhesion molecule expression, but also in the maintenance of an inflammatory loop through the increase in proinflammatory cytokine secretion.


Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases.
Prospective observational studies support the use of long-chain omega-3 polyunsaturated fatty acids (PUFAs) in the primary prevention of atherosclerotic cardiovascular disease; however, randomised controlled trials, have often reported neutral findings. There is a long history of debate about the potential harmful effects of a high intake of omega-6 PUFAs, although this idea is not supported by prospective observational studies or randomised controlled trials. Health effects of PUFAs might be influenced by Δ-5 and Δ-6 desaturases, the key enzymes in the metabolism of PUFAs. The activity of these enzymes and modulation by variants in encoding genes (FADS1-2-3 gene cluster) are linked to several cardiometabolic traits. This Review will further consider non-genetic determinants of desaturase activity, which have the potential to modify the availability of PUFAs to tissues. Finally, we discuss the consequences of altered desaturase activity in the context of PUFA intake, that is, gene-diet interactions and their clinical and public health implications.


The influence of a simulated game on muscular strength in female high-school and collegiate softball pitchers.
Softball pitchers often pitch several games within a day and over consecutive days during a competitive season. High volumes of pitches thrown can decrease muscular strength, resulting in less proximal force generation and upper extremity compensation to maintain performance. Therefore, the purpose of this study was to assess upper and lower extremity muscular strength after pitching in a simulated game. Fourteen softball pitchers (17.9 ± 2.3 years, 166.4 ± 8.7 cm, 72.2 ± 12.6 kg) completed baseline isokinetic strength assessment for knee, hip, trunk and pitching elbow flexion and extension as well as trunk rotation. Seven days later, participants pitched a simulated game consisting of 105 fastballs prior to repeating all strength assessments. Changes in muscular strength were assessed using paired samples t-tests, with significance set a priori as p ≤ 0.05. Normalised (%BW) stride leg knee extension peak torque was significantly higher (p = 0.020) post-simulated game (75.1 ± 24.6%BW) as compared to baseline (64.0 ± 19.5%BW) and trunk flexion peak torque was significantly higher (p = 0.009) post-simulated game (84.8 ± 47.0%BW) as compared to baseline (63.5 ± 47.1%BW). This study showed an increase in knee extension and trunk flexion strength after an acute bout of pitching. The findings give insight into muscular changes following pitching which can assist in appropriate softball training and recovery.


Photoinduced three-component coupling reactions of electron deficient alkenes, dienes and active methylene compounds.
The irradiation of aqueous acetonitrile solutions, containing electron deficient alkenes, dienes and active methylene compounds along with sodium or cesium carbonate and catalytic amounts of phenanthrene or pyrene, gives rise to the formation of novel three-component coupling products and diene dimers. Cinnamonitrile and benzylidenemalononitrile and its derivatives serve as electron-acceptors; 2,5-dimethyl-2,4-hexadiene and malononitrile anion serve as electron donors in this process. Based on the results of UV-vis absorption spectroscopy and the calculated ΔG values for single electron transfer (SET), mechanisms are proposed for the coupling reaction involving photoinduced electron transfer (PET) between the electron deficient alkenes and dienes or malononitrile anion via direct excitation of electron deficient alkenes or redox photosensitization using phenanthrene or pyrene serving as a photosensitizer.


The malignant primate?
Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century.


Rapamycin Suppresses Penile NADPH Oxidase Activity to Preserve Erectile Function in Mice Fed a Western Diet.
The mechanistic target of rapamycin (mTOR) is a nutrient-sensitive cellular signaling kinase that has been implicated in the excess production of reactive oxygen species (ROS). NADPH oxidase-derived ROS have been implicated in erectile dysfunction pathogenesis. The objective of this study was to determine if mTOR is an activator of NADPH oxidase in the penis and to determine the functional relevance of this pathway in a translationally relevant model of diet-induced erectile dysfunction. Male mice were fed a control diet or a high-fat, high-sucrose Western style diet (WD) for 12 weeks and treated with vehicle or rapamycin for the final 4 weeks of the dietary intervention. Following the intervention, erectile function was assessed by cavernous nerve-stimulated intracavernous pressure measurement, in vivo ROS production was measured in the penis using a microdialysis approach, and relative protein contents from the corpus cavernosum were determined by Western blot. Erectile function was impaired in vehicle treated WD-mice and was preserved in rapamycin treated WD-mice. Penile NADPH oxidase-mediated ROS were elevated in WD-mice and suppressed by rapamycin treatment. Western blot analysis suggests mTOR activation with WD by increased active site phosphorylation of mTOR and p70S6K, and increased expression of NADPH oxidase subunits, all of which were suppressed by rapamycin. These data suggest that mTOR is an upstream mediator of NADPH oxidase in the corpus cavernosum in response to a chronic Western diet, which has an adverse effect on erectile function.


Effect of dual screws across the vertebral neurocentral synchondrosis on spinal canal development in an immature spine: a porcine model.
Questions remain as to the effect of pedicle screws on spinal canal development in young children. The purpose of this study was to determine the effects of unilateral placement of dual screws across the neurocentral synchondrosis on spinal canal development as assessed with histological analysis and measurement of the canal dimensions in an immature pig model. Twenty-seven one-month-old pigs were assigned to two groups on the basis of the surgical approach used to place unilateral double screws that did or did not cross the neurocentral synchondrosis. In one group, sixteen pigs underwent a posterior approach from T7 to T14 and were divided into four subgroups: no screws (without screw fixation), short screws (dual pedicle screws that did not cross the neurocentral synchondrosis), long screws (dual pedicle screws that crossed the neurocentral synchondrosis), and screw removal (long dual pedicle screws that were removed at six weeks postoperatively). In the other group, eleven pigs underwent an anterior approach, with double vertebral body screws placed via thoracotomy. These animals were divided into two subgroups: short screws (dual vertebral body screws that did not cross the neurocentral synchondrosis) and long screws (dual vertebral screws that crossed the neurocentral synchondrosis). All animals were killed at seventeen weeks. The total area, width, and depth of the spinal canal were measured on axial computed tomography (CT) images. Quantitative histological analysis was performed to measure the rate of neurocentral synchondrosis closure. Use of unilateral double pedicle screws across the neurocentral synchondrosis through a posterior approach resulted in 97% neurocentral synchondrosis closure with a 20% decrease in the canal area and a 15% decrease in the canal depth. Use of unilateral double vertebral body screws across the neurocentral synchondrosis through an anterior approach resulted in 71% neurocentral synchondrosis closure with a 15% decrease in the canal area and an 8% decrease in the canal width. Unilateral double pedicle screws crossing the neurocentral synchondrosis adversely affected spinal canal growth in immature pigs. Pedicle screws should be used with caution in very young children, and a delay in surgical treatment until they are older should be considered.


Molecular analysis of codon 548 in the rpoB gene involved in Mycobacterium tuberculosis resistance to rifampin.
Most Mycobacterium tuberculosis rifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance-determining region (RRDR) in the gene rpoB. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinant Mycobacterium smegmatis and M. tuberculosis isolates carrying mutated rpoB (Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of the rpoB gene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.


Epilepsy and pregnancy.
Since 1963, the association between antiepileptic drugs (AEDs) and congenital malformations in the offspring of women with epilepsy has received attention. A number of articles reported affirmative as well as some negative findings regarding an increased risk of congenital malformations. Although a consensus has not been regarding the presence of the specific malformation syndromes in relation to individual AEDs, such as fetal hydantoin syndrome, it is evident that women taking AEDs carry a two- to sevenfold higher risk of congenital malformations than do the general population. In most recent studies, special attention has been placed on polytherapy, including the specific AED, or AED combinations, and high AED serum concentrations, responsible for the higher risk of congenital malformations. Based on these cumulative results, therapy guidelines for women of childbearing age with epilepsy have been established.


Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.
Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.


Antibody array profiling reveals serum TSP-1 as a marker to distinguish benign from malignant prostatic disease.
Blood protein markers that provide more accurate or earlier diagnosis of prostate cancer should have a positive impact on prostate cancer treatment and management. Serum samples from control subjects and patients with benign or malignant prostatic disease were analyzed on antibody arrays targeting multiple candidate prostate cancer markers and detected with two-color, rolling-circle amplification (TC-RCA). The measurements of certain antibodies were validated using immunoblots, immunoprecipitation/mass spectrometry, and sandwich immunoassays. Several potential disease-associated protein alterations were uncovered. The most significant was thrombospondin-1, which was strongly elevated in patients with benign prostatic disease and repressed in patients with prostate cancer. Thrombospondin-1 levels did not correlate with prostate-specific antigen (PSA) levels and differentiated benign from malignant disease with 79% sensitivity and 81% specificity. The measurement of thrombospondin-1 could be used to assist the decision to obtain a biopsy in men with suspected prostate cancer, which could lead to a reduction in the number of unnecessary prostatic biopsies.


Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study.
Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed. To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS. Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003. Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1. Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results. Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better oxygen saturation (P =.02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine kinase levels (P =.03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone. In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.


Trimestral changes of seizure frequency in pregnant epileptic women.
The aim of this study was to assess the influence of pregnancy on trimestral frequency of epileptic seizures. The seizure frequency was studied retrospectively in 50 pregnant epileptic women compared to one year before the onset of pregnancy, for each trimester of pregnancy separately, and for the whole duration of pregnancy. In the first trimester 18% of the pregnant epileptic women had an increased seizure frequency. There was no change in seizure frequency in 56% of pregnancies. In 26% of the pregnant women the number of seizures was decreased. In the second trimester, pregnancy did not influence seizure frequency in 60% of the pregnancies; 16% of the women had increased frequency of seizures and 24% had decreased frequency. In the third trimester, 20% of the pregnant epileptic women had higher seizure frequency. In 56% of the women no change in seizure frequency was recorded during pregnancy. For the entire period of pregnancy, 22% of the pregnant epileptic women had an increased seizure frequency, 54% had no change, and 24% had lower frequency as compared to one year before conception. No difference of seizure frequency was noted between trimesters and the whole course of pregnancy.


Pseudorhodoferax aquiterrae sp. nov., isolated from groundwater.
A Gram-negative, rod-shaped, motile, non-spore-forming and poly-β-hydroxybutyrate-containing bacterial strain, designated NAFc-7(T), was isolated from groundwater in Taiwan and was characterized using a polyphasic taxonomic approach. Growth occurred at 15-40 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 6.0-7.0) and with 0-3 % NaCl (optimum, 0-1 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain NAFc-7(T), together with Pseudorhodoferax soli TBEA3(T) (98.2 % sequence similarity) and Pseudorhodoferax caeni SB1(T) (98.0 %), formed a deep line within the family Comamonadaceae. Strain NAFc-7(T) contained summed feature 3 (comprising C(16 : 1)ω7c and/or C(16 : 1)ω6c), C(16 : 0) and C(17 : 0) cyclo as the predominant fatty acids. The major 3-hydroxy fatty acid was C(10 : 0) 3-OH. The major isoprenoid quinone was Q-8 and the DNA G+C content was 67.6 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylserine and an uncharacterized phospholipid. The DNA-DNA relatedness of strain NAFc-7(T) with respect to recognized species of the genus Pseudorhodoferax was less than 70 %. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain NAFc-7(T) represents a novel member of the genus Pseudorhodoferax, for which the name Pseudorhodoferax aquiterrae sp. nov. is proposed. The type strain is NAFc-7(T) (= BCRC 80210(T) = LMG 26333(T) = KCTC 23314(T)).


Perceptions and attitudes of critical care training and careers among United States surgical residents: who wants to be a surgical intensivist?
Less than 50 per cent of surgical critical care (SCC) fellowship positions are filled each year. We surveyed senior surgical residents to determine their opinions regarding a career in SCC and acute care surgery. A survey was sent to 1348 postgraduate year 3, 4, and 5 residents in the United States. Two hundred fifty-one surveys were returned (19% response rate). Whereas 78 per cent were planning to complete a fellowship, 21 per cent expressed interest in SCC. Fifty-six per cent plan to handle SCC problems only for their own patients, whereas 39 per cent plan to turn this management over to a critical care provider. SCC fellowships were considered to be potentially more appealing if the following changes could be made to the existing structure: adding more general surgery (70% of respondents); adding more trauma experience (50%); adding emergency neurosurgery (44%); adding more emergency orthopedics (42%); or decreasing months of critical care (36%). Increasing salary enhanced appeal for 82 per cent. SCC has limited appeal for most senior surgical residents. Theoretical expansion of surgical critical fellowships to include more general or trauma surgery (acute care surgery) increased the level of interest among senior surgical residents.


Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas.
Perfusion magnetic resonance imaging (MRI) is increasingly used in the evaluation of brain tumors. Relative cerebral blood volume (rCBV) is usually obtained by dynamic susceptibility contrast (DSC) MRI using normal appearing white matter as reference region. The emerging perfusion technique arterial spin labelling (ASL) presently provides measurement only of cerebral blood flow (CBF), which has not been widely used in human brain tumor studies. To assess if measurement of blood flow is comparable with measurement of blood volume in human biopsy-proven gliomas obtained by DSC-MRI using two different regions for normalization and two different measurement approaches. Retrospective study of 61 patients with different types of gliomas examined with DSC perfusion MRI. Regions of interest (ROIs) were placed in tumor portions with maximum perfusion on rCBF and rCBV maps, with contralateral normal appearing white matter and cerebellum as reference regions. Larger ROIs were drawn for histogram analyses. The type and grade of the gliomas were obtained by histopathology. Statistical comparison was made between diffuse astrocytomas, anaplastic astrocytomas, and glioblastomas. rCBF and rCBV measurements obtained with the maximum perfusion method were correlated when normalized to white matter (r = 0.60) and to the cerebellum (r = 0.49). Histogram analyses of rCBF and rCBV showed that mean and median values as well as skewness and peak position were correlated (0.61 < r < 0.93), whereas for kurtosis and peak height, the correlation coefficient was about 0.3 when comparing rCBF and rCBV values for the same reference region. Neither rCBF nor rCBV quantification provided a statistically significant difference between the three types of gliomas. However, both rCBF and rCBV tended to increase with tumor grade and to be lower in patients who had undergone resection/treatment. rCBF measurements normalized to white matter or cerebellum are comparable with the established rCBV measurements used for the clinical evaluation of cerebral gliomas.


Developing a mandate for change: planning as a political process.
The three main questions dealt with in this article are: 'why have community participation in planning?' 'what is community participation?' and 'how can community participation be practised?' Planning in this context should be understood in a strategic sense as social policy development and implementation at a regional level. In answer to the first question, two common approaches to social planning and their shortcomings are briefly discussed, with reference to a taxonomy from Alan Walker's book Social Planning, A Strategy for Socialist Welfare. Community participation in social planning is a key characteristic of an alternative approach which addresses or avoids altogether the fundamental shortcomings of the other two. Issues of the practice of community participation in regional planning are examined through a description and analysis of the planning process undertaken by the Western Metropolitan Region of the Health Department Victoria. Some general conclusions regarding current trends in policy formation and public sector administration are also drawn.


[Analysis and comparison of various quality protocols for radiotherapy linear accelerators].
The main parameters determining the quality of an electron beam produced by a linear accelerator for medical use were considered in this study, particularly: flatness, symmetry and uniformity. We analyzed and compared several protocols issued by national and international associations (such as the AAPM, IPSM, ICRU, NACP), the software protocol developed for the measurement system we used (Multidata) and the measurement instructions recommended by the accelerator manufacturer (Siemens). The above associations issue quality protocols to ensure system performances suitable for medical use, to increase patient safety and to improve the treatment outcome. Radiation therapy safety and improvement depend on correct dose measurements and dose distribution in the treated volume. Once the dose value per monitor unit ratio (Gy/M.U.) is determined, controls are necessary to be sure that the value does not change in time and that the dose distribution has the same effect in the whole treated volume. Our goal is to point out the differences and the affinities in the definition of the parameters, which change slightly in the different protocols, and to study the origin of the differences found when the experimental results were compared. Another important issue is represented by the frequency of quality controls, which are definitely different from the fast checks which are often performed. In conclusion, some suggestions are provided for the choice of the quality protocol to follow.