Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development.
To conduct a systematic review of evidence surrounding the effects of exercise training on physical fitness, mobility, fatigue, and health-related quality of life in adults with multiple sclerosis (MS). The databases included EMBASE, 1980 to 2011 (wk 12); Ovid MEDLINE and Ovid OLDMEDLINE, 1947 to March (wk 3) 2011; PsycINFO, 1967 to March (wk 4) 2011; CINAHL all-inclusive; SPORTDiscus all-inclusive; Cochrane Library all-inclusive; and Physiotherapy Evidence Database all-inclusive. The review was limited to English-language studies (published before December 2011) of people with MS that evaluated the effects of exercise training on outcomes of physical fitness, mobility, fatigue, and/or health-related quality of life. One research assistant extracted data and rated study quality. A second research assistant verified the extraction and quality assessment. From the 4362 studies identified, 54 studies were included in the review. The extracted data were analyzed using a descriptive approach. There was strong evidence that exercise performed 2 times per week at a moderate intensity increases aerobic capacity and muscular strength. The evidence was not consistent regarding the effects of exercise training on other outcomes. Among those with mild to moderate disability from MS, there is sufficient evidence that exercise training is effective for improving both aerobic capacity and muscular strength. Exercise may improve mobility, fatigue, and health-related quality of life.


Effect of inducible nitric oxide synthase on intestinal microcirculation in endotoxic shock.
To investigate the changes of intestinal microcirculation in endotoxic shock and the effect of inducible nitric oxide synthase (iNOS) on intestinal microcirculation, endotoxic shock was induced by intravenous injection of lipopolysaccharide (LPS) in mice. Mean arterial pressure (MAP) was monitored throughout the experimental procedure. The velocity and flux of red blood cell (RBC) in villus tip arteriole and capillaries were measured by FITC-labeled erythrocytes and intravital microscopy. The effect of iNOS was determined by targeted disruption of mice iNOS-gene and administration of S-methylthiourea sulfate (SMT), a selective inhibitor of iNOS, before LPS injection. No significant differences in MAP, RBC velocity and flux at baseline were found among wild type mice, SMT pretreated mice and iNOS-gene knockout mice. LPS induced a dramatic fall of MAP in wild type mice. The decrease of MAP was significantly restored in iNOS-gene knockout mice and in wild type mice received SMT before LPS injection. The velocity and flux of RBC in villus tip arteriole and capillaries decreased markedly after LPS injection in wild type mice, while significantly higher velocity and flux of RBC were found in iNOS-gene knockout mice and SMT-pretreated mice both 60 and 120 min after LPS injection. The results demonstrate that iNOS plays an essential role in the intestinal microcirculation disturbance which occurs in endotoxic shock.


Outcomes following childhood arterial ischaemic stroke: a Delphi Consensus on what parents want from future research.
Currently there are few population-based data on the outcomes of stroke in childhood, and no data on what parents want from such research. We conducted a Delphi Consensus Process among parents of children (n = 26) who had suffered an arterial ischaemic stroke to investigate which research outcomes they think are most important to follow up, and what methods of assessment they would find most acceptable. A postal Delphi Consensus Process was conducted. The Delphi panel reached consensus that motor, cognitive and communication outcomes are the most important outcome domains to assess. They strongly preferred home visits over hospital visits or telephone interview. The majority were happy with assessment visits lasting up to 1.5 h. Ongoing concerns for panel members related to the cause of the original stroke, the risk of recurrence and the long term outcome for their child. Future outcome studies should preferably assess outcomes at home and focus on children's motor, cognitive and communication abilities. There is an ongoing need to clarify issues with regards to the likely cause of children's strokes and their risk of recurrence.


Price: a market signal of quality in health care insurance policies?
Choosing a good quality health insurance policy is important for most individuals in this country. The choice task is however, made quite complicated by the existence of many alternative policies which are each characterized by multiple attributes. This paper examines whether the price (i.e., premium) of a health insurance plan can give a reliable signal about the objective quality level of the plan. Empirical analysis of real-world data shows that overall, price is positively correlated with such quality. Statistical significance tests are conducted to separately evaluate such correlations for different categories of health insurances. Finally, the empirical results are used to indicate implications for consumer decision making.


A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression.
High-frequency left-side repetitive transcranial magnetic stimulation (rTMS) and low-frequency stimulation to the right prefrontal cortex have both been shown to have antidepressant effects, but doubts remain about the magnitude of previously demonstrated treatment effects. The authors evaluated sequentially combined high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex for treatment-resistant depression. The authors conducted a 6-week double-blind, randomized, sham-controlled trial in 50 patients with treatment-resistant depression. Three trains of low-frequency rTMS to the right prefrontal cortex of 140 seconds' duration at 1 Hz were applied daily, followed immediately by 15 trains of 5 seconds' duration of high-frequency left-side rTMS at 10 Hz. Sham stimulation was applied with the coil angled at 45 degrees from the scalp, resting on the side of one wing of the coil. The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale. There was a significantly greater response to active than sham stimulation at 2 weeks and across the full duration of the study. A significant proportion of the study group receiving active treatment met response (11 of 25 [44%]) or remission (nine of 25 [36%]) criteria by study end compared to the sham stimulation group (two of 25 [8%] and none of 25 respectively). Sequentially applying both high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex, has substantial treatment efficacy in patients with treatment-resistant major depression. The treatment response accumulates to a clinically meaningful level over 4 to 6 weeks of active treatment.


Control of insulin secretion by GLP-1.
Stimulation of insulin secretion by glucagon-like peptide-1 (GLP-1) and other gut-derived peptides is central to the incretin response to ingesting nutriments. Analogues of GLP-1, and inhibitors of its breakdown, have found widespread clinical use for the treatment of type 2 diabetes (T2D) and obesity. The release of these peptides underlies the improvements in glycaemic control and disease remission after bariatric surgery. Given therapeutically, GLP-1 analogues can lead to side effects including nausea, which limit dosage. Greater understanding of the interactions between the GLP-1 receptor (GLP-1R) and both the endogenous and artificial ligands therefore holds promise to provide more efficacious compounds. Here, we discuss recent findings concerning the signalling and trafficking of the GLP-1R in pancreatic beta cells. Leveraging "bias" at the receptor towards cAMP generation versus the recruitment of β-arrestins and extracellular signal-regulated kinases (ERK1/2) activation may allow the development of new analogues with significantly improved clinical efficacy. We describe how, unexpectedly, relatively low-affinity agonists, which prompt less receptor internalisation than the parent compound, provoke greater insulin secretion and consequent improvements in glycaemia.


p-sd Shell gap reduction in neutron-rich systems and cross-shell excitations in 20 O.
Excited states in 20O were populated in the reaction 10Be(14C,alpha) at Florida State University (FSU). Charged particles were detected with a particle telescope consisting of 4 annularly segmented Si surface barrier detectors and gamma radiation was detected with the FSU gamma detector array. Five new states were observed below 6 MeV from the alpha-gamma and alpha-gamma-gamma coincidence data. Shell model calculations suggest that most of the newly observed states are core-excited 1p-1h excitations across the N=Z=8 shell gap. Comparisons between experimental data and calculations for the neutron-rich O and F isotopes imply a steady reduction of the p-sd shell gap as neutrons are added.


Persistently positive gliadin antibodies without transglutaminase antibodies in the elderly: gluten intolerance beyond coeliac disease.
The specificity of the conventional gliadin antibody test is considered low. We explored whether gliadin antibody(AGA)-positivity without tissue transglutaminase antibodies (tTGA) is persistent in the elderly population and whether such positivity indicates overt or potential coeliac disease in genetically predisposed individuals. AGA and tissue transglutaminase antibody were measured in 2089 elderly individuals twice with a three-year interval. AGA-positive but tissue transglutaminase antibody-negative subjects with coeliac-type human leucocyte antigen (HLA) were examined and underwent gastroduodenal endoscopy (cases). Small-bowel mucosal villous morphology and densities of CD3+ and γδ+ intraepithelial lymphocytes and the occurrence of tissue transglutaminase-specific IgA deposits were analysed. Randomly selected persistently AGA-negative age- and sex-matched subjects served as controls. AGA-positivity was persistent in 81% of those initially positive. Amongst the 49 clinically studied and 36 endoscopied cases only one (2.8%) had coeliac disease. Many (54%) showed signs of inflammation in the biopsy, without villous atrophy. Coeliac-type HLA was not over-represented in the persistently AGA-positive compared to the general population. Persistently AGA-positive coeliac-type HLA-positive subjects had more gastrointestinal symptoms than AGA-negative controls. AGA-positivity is often persistent. Overt coeliac disease is seldom found behind persistent AGA-positivity, but this characteristic is associated with mucosal inflammation and gastrointestinal symptoms at least in HLA-positive individuals.


Separation and preconcentration of inorganic arsenic species in natural water samples with 3-(2-aminoethylamino) propyltrimethoxysilane modified ordered mesoporous silica micro-column and their determination by inductively coupled plasma optical emission spectrometry.
A simple and sensitive method using micro-column packed with 3-(2-aminoethylamino) propyltrimethoxysilane (AAPTS) modified ordered mesoporous silica combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for the speciation of inorganic arsenic (As(III) and As(V)) has been developed. The adsorption behaviors of As(III) and As(V) on AAPTS modified ordered mesoporous silica were investigated. It was found that As(V) can be selectively adsorbed on the micro-column within pH of 3-9, while As(III) could not be retained in the studied pH range and passed through the micro-column directly. Total inorganic arsenic was extracted after the oxidation of As(III) to As(V) with 50.0 micromol L(-1) KMnO(4). The assay of As(III) was based on subtracting As(V) from total As. The effect of various parameters on the separation/preconcentration of As(III) and As(V) have been investigated and the optimal experimental conditions were established. The adsorption capacity of AAPTS modified ordered mesoporous silica for As(V) was found to be 10.3 mg g(-1). The detection limit of the method for As(V) was 0.05 microg L(-1) with an enrichment factor of 100, and the relative standard deviation (R.S.D.) was 5.7% (n=7, C=1.0 microg L(-1)). In order to validate the developed method, a certified reference material GSBZ50004-88 environmental water sample was analyzed and the determined values were in good agreement with the certified values. The proposed method was successfully applied to the speciation analysis of inorganic arsenic in natural water samples.


AIDS defining conditions in Africans resident in the United Kingdom.
A retrospective study of 55 HIV-1 seropositive African patients living in the UK, seen between January 1986 and November 1993, showed a total of 26 (47%) patients with AIDS. Thirty-one (56%) had symptomatic HIV disease at the time of presentation of whom 19 (34.5%) had an AIDS defining condition. Tuberculosis was the most common AIDS defining illness, accounting for 27% of all initial AIDS diagnoses, followed by by Pneumocystis carinii pneumonia and oesophageal candidiasis in 19% each and chronic mucocutaneous genital herpes in 15%. The mean CD4 count at the time of the first AIDS defining event was 91 x 10/mm3 (range 4-320 x 10/mm3). The profile of AIDS defining illnesses was different to published data of homosexual men and injecting drug users in the UK. This has practical implications when considering differential diagnoses and screening as well as prophylaxis for opportunistic infections in this group of patients.


Multiple insertions of fimbrial operons correlate with the evolution of Salmonella serovars responsible for human disease.
On centisome 7, Salmonella spp. contain a large region not present in the corresponding region of Escherichia coli. This region is flanked by sequences with significant homology to the E. coli tRNA gene aspV and the hypothetical E. coli open reading frame yafV. The locus consists of a mosaic of differentially acquired inserts forming a dynamic cs7 region of horizontally transferred inserts. Salmonella enterica subspecies I, responsible for most Salmonella infections in warm-blooded animals, carries a fimbrial gene cluster (saf) in this region as well as a regulatory gene (sinR). These genes are flanked by inverted repeats and are inserted in another laterally transferred region present in most members of Salmonella spp. encoding a putative invasin (pagN ). S. enterica subspecies I serovar Typhi, the Salmonella serovar that causes the most severe form of human salmonellosis, contains an additional insert of at least 8 kb in the sinR-pagN intergenic region harbouring a novel fimbrial operon (tcf ) similar to the coo operon encoding the CS1 fimbrial adhesin expressed by human-specific enterotoxigenic E. coli. It is suggested that the multiple insertions of fimbrial genes that have occurred in the cs7 region have contributed to phylogenetic diversity and host adaptation of Salmonella spp.


Pathogenicity analysis of variations and prenatal diagnosis in a hereditary coagulation factor XIII deficiency family.
Prenatal diagnosis (PND) procedure is urgent to be established for timely management and fatal consequence prevention of factor XIII deficiency (FXIIID), and variations data among Chinese are very scanty. We aimed to find a novel mutation among Chinese and establish a rapid and precise PND procedure with pathogenicity analysis to contribute to the prevention of postpartum hemorrhage in pregnant women and central nervous system bleeding in newborns. FXIIID was diagnosed by qualitative and quantitative tests of clot solubility test and enzyme-linked immunosorbent assay, respectively. Variations were detected by direct sequencing of F13A and F13B genes in the pedigree and the unborn fetus. Pathogenicity assessment of variations was based on American College of Medical Genetics and Genomics Guidelines. Ten variants in the F13A gene including a novel missense mutation in exon 10, a nonsense mutation in exon 4, a missense mutation in exon 12, 2 missense mutations in exon 14, 3 polymorphisms in intron 10, 2 polymorphisms in intron 14 were detected. Two variants in the F13B gene including a polymorphism in 3'UTR and a synonymous mutation were detected. The compound heterozygous mutations of the nonsense mutation and a novel missense mutation of the F13A gene caused the deficiency in proband, and the fetus which was evaluated to be unaffected by PND was born successfully and the results were verified by follow-up visits. We first established the PND procedure with pathogenicity assessment in FXIIID patients. The F13A gene mutations' spectrum of the Chinese Han population was enriched.


When approved is not enough: development of a supervision consultation model.
The dramatic increase in the literature that addresses family therapy training and supervision over the last decade has been predominantly in the area of theory, rather than practice. This article describes the development of a meta-supervisory learning context for approved supervisors and provides examples of interactions between supervisors that subsequently influenced both therapy and supervision. We delineate the assumptions that inform our work and offer specific guidelines for supervisors who wish to implement a similar model in their own contexts. We provide suggestions for a proactive refiguring of supervision that may have profound effects and benefits for supervisors and supervisees alike.


Mouse embryonic stem (ES) cell culture.
Mouse embryonic stem (ES) cells are used to generate mouse mutants by gene targeting and blastocyst-mediated transgenesis. ES cells must be cultured under conditions that prevent differentiation to maintain their ability to transmit altered alleles by contributing to the germ line. This unit describes one of the most common methods for culturing ES cells using mouse embryo fibroblast (MEF) feeder layers and recombinant leukemia inhibitory factor (LIF) to prevent differentiation.


Effect of flapless surgery on single-tooth implants in the esthetic zone: a randomized clinical trial.
Implant therapy is a highly predictable treatment option; however, insufficient data exist to show whether flapless implant surgery provides better esthetic outcomes and less bone loss than implant surgery with a flap approach. In this randomized, controlled study comparing the flapless and traditional flap protocol for implant placement, 24 patients received a single implant in the anterior maxillary region. A cone beam computed tomography-aided surgical guide was used for implant placement surgery for both groups. Implants were restored using a one-piece, screw-retained ceramic crown at 3 months. Radiographic and clinical measurements were assessed at baseline (implant placement) and at 3 (crown placement), 6, 9, and 15 months. Clinical parameters evaluated were plaque index, gingival index, papillary index (PPI) (0 = no papilla, 1 = less than half, 2 = more than half but not complete, 3 = complete fill, and 4 = overfill), marginal tissue levels, biotype, width of keratinized tissue, and soft tissue thickness. Implant success rate was 92% in both groups. Mean PPI values for the flap control group and flapless test group were 2.38 ± 0.51 versus 2.31 ± 0.48 at crown placement (P = 0.68) and 2.52 ± 0.52 versus 2.64 ± 0.54 at 15 months (P = 0.42), respectively. PPI increased over time in both groups, although the flapless group had a significantly larger change in PPI from crown placement to 6 and 9 months (P <0.01). Crestal bone levels in the flap group were more apical in relation to the implant platform than those in the flapless group for the duration of the study. No differences among groups were noted for all other measurements. Both flapless and flap implant placement protocols resulted in high success rates. A flapless protocol may provide a better short-term esthetic result, although there appears to be no long-term advantage.


[Effect of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and aortic tension induced by septic shock in rats].
To investigate the effect of three types of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and thoracic aorta tension induced by septic shock in rats. We used cecal ligation and puncture (CLP) method to establish septic shock in rats, and the three types of nitric oxide synthase inhibitors were injected after CLP. The carotid artery was cannulated and connected to a pressure transducer to determine mean arterial blood pressure (MABP). Ventricular dynamic parameters were determined following intraventricular cannulation via the carotid artery, including heart rate (HR), left ventricular developed pressure (LVDP), maximal rise/fall velocity of ventricular pressure (+/- dP/dt(max)). Isolated thoracic rings were mounted on an organ bath and the tension of the vessel was recorded. (1) After using L-NAME, AMG and 7-NI the mortality decreased to 50.0%, 37.5%, and 42.1%, respectively (from 65.2% in septic shock rats); (2) The MABP in septic shock rats partly recovered after using the NOS inhibitors, all ventricular dynamic parameters partly recovered after using the inhibitors; (3) The hyporeactivity of endothelium-denuded aortic rings to vasoconstrictors induced by septic shock was partly recovered by pretreatment with the inhibitors. However, only L-NAME or 7-NI could inhibit the decrease of vasoconstriction induced by septic shock in endothelium-intact aortic rings. The three types of nitric oxide synthase inhibitors can improve the hemodynamic parameters and vasoconstriction responsiveness of endothelium-denuded aorta of septic shock rats. Furthermore, L-NAME and 7-NI improve the responsiveness of endothelium-intact aorta.


Transplantation.
The history of solid organ transplantation is traced from its beginnings in the 19th century to the beginning of the 21st century. Surgical techniques, advances in immunology, and a review of major immunosuppressive milestones are reviewed. Over the last 50 years, transplantation has moved from experimental to accepted clinical therapy. The technology of transplantation has been widely disseminated throughout the United States. This paper reviews the major ethical and social problems that still need to be addressed in regards to transplantation. These include organ supply, organ distribution, access to care, funding, and xenotransplantation.


[Logopedic disorders in children with epilepsy].
Eighty five children with partial epilepsy were studied neuropsychologically, logopedically, neurologically and electrophysiologically. Speech function evaluation was conducted regarding age, mental retardation and severity of the underlying disease. It is shown that 53% children have logopedic disorders, in 35% cases these disorders were severe such as speech delay or general speech underdevelopment. Characteristics of the disorders correlated with severity of mental retardation of the child and the disease severity.


Human and murine B-cells recognize the HBeAg/beta (or HBe2) epitope as a linear determinant.
The complete amino acid (aa) sequence of the hepatitis B virus (HBV) core protein (HBcAg), deduced from the genome of the HBV ayw subtype, was synthesized as decapeptides with five overlapping aas. The peptides were tested for reactivity with monoclonal antibodies (mAbs) to the beta (or HBe2) epitope of hepatitis B e antigen (HBe/b mAbs; 57/8, 78/3, 141/158 and 141/207). Cross-competition between the mAbs with a mAb to the HBe/alpha epitope (or HBe1) and an anti-HBc mAb showed that all the HBe/b mAbs specifically inhibited human anti-HBe/b binding. Screening the HBc/e peptides showed that all anti-HBe/b mAbs recognized a peptide covering the residues 126-135. Three of the mAbs, 78/3, 141/152 and 141/207, had a less restricted reactivity than the other two, suggesting the recognition of the HBe/b as a discontinuous determinant. Fine mapping of the region aa 126-135 was performed by synthesizing decapeptides with nine overlapping aas, covering residues aa 121-140. All mAbs, except 78/3, reacted with the linear sequence TPPAYR, at residues 128-133. An additional set of peptides was synthesized, where the six aas within the epitope 128-133 were substituted in turn by the other 19 possible aas. By this approach, the essential aas for mAb 57/8 were found to be the sequence of PPA at residues 129-131, and for mAb 141/158 the sequence PP-Y, at residues 129, 130 and 132, respectively. Human recognition of the linear HBe/b epitope was investigated by using a peptide covering residues 121-140 (p 33). Thirty-one sera from chronic carriers of HBsAg, of which seven were positive for HBeAg and the remaining 24 for anti-HBe, were investigated. Of the sera with HBeAg, two had low levels of anti/-HBe/b in the p 33 assay. Out of the sera with anti-HBe, eight were positive in the p 33 EIA. Thus, murine monoclonals and human sera may recognize the HBe/b epitope as a linear determinant residing around aa 130.


Obesity, Inflammation, and Cancer.
Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.


Molecular epidemiology: a new perspective for the study of toxic exposures in man. A consideration of the influence of genetic susceptibility factors on risk in different lung cancer histologies.
This data in the aggregate suggests that the 3 best studied genetic susceptibility factors (CYP2D6 extensive metabolizers, GST mu null phenotype, and CYP1A1 "mutant" alleles in Asians only) constitute greater risk factors for the more smoking related histologies of lung cancer, but not for adenocarcinoma. The epidemiologic evidence for a these genetic susceptibility factors in tobacco-related cancer is suggestive but not determinant. A consensus estimate of relative risk for extensive metabolizers of debrisoquine is around 2. Variability in study results depend on a number of factors which include: assay misclassification, non-correspondence of phenotype/genotype in certain subjects, disease heterogeneity, exposure variation, ethnic and racial variation. Future studies should emphasize: a high quality approach to data gathering, careful attention to epidemiologic design, and the use of intermediate markers where feasible. Investigators should consider the use of multiple genetic markers since PCR approaches can make this an efficient approach. A meta-analysis may serve to illuminate points of heterogeneity between studies. New discoveries should provide opportunities to explore for analogous associations in other malignancies. It may be speculated that the "specificity" of the association observed for each of the genetic factors tends to support the general causal nature of the hypothesis. The fact that each shares the histologic preference at least suggests that a common mechanism may be operative. The observation that the tobacco-cancer association, though clearly present, is weaker for adenocarcinoma than for the other lung cancer histologies, suggests that the underlying mechanism involves some interaction of the genetic trait with exposure to tobacco smoking, and suggests further attention to this factor to elucidate differences in risk estimates for genetic susceptibility factors among different studies.


Cardio-Kidney-Damage: a unifying concept.
The perceived global rise in chronic kidney disease (CKD) has been met with apprehension and skepticism. It has been argued by some that we are facing a CKD 'epidemic' and by others that the high prevalence of CKD observed in different communities may be the result of flawed screening methods and tools. Both estimation of glomerular filtration rate and determination of microalbuminuria as markers of CKD have been criticized. Also, many commented that CKD, as currently defined, was primarily a disease of elderly people with reduced kidney function. Some described this as a physiological age-related decline in kidney function while others consider it to be pathological, warranting the label of a disease. In this review, an attempt is made to reconcile different views by examining some of the available evidence and to conclude that the high prevalence of 'CKD' in the elderly population is likely to reflect the underlying high prevalence of overt and subclinical atherosclerosis and cardiovascular disease. This leads to the conclusion that CKD is a reflection of diffuse and age-related Cardio-Kidney-Damage (C-K-D) that may not warrant the label of disease but certainly justifies attention with reduction of lifelong cardiovascular risks and careful evaluation and treatment.


Radionuclides in shoreline waters of the northeast Irish Sea.
The shoreline waters of the Irish Sea along the Cumbrian coast near the British Nuclear Fuels plc works at Sellafield have been sampled at three locations over a 31/2 year period from December 1980. The particulate content was analysed for 238Pu, 239 + 240Pu, 241Am, 137Cs and stable Al. In some cases the radionuclide concentrations in filtered seawater were also determined. The results showed that the suspended particulate loads were high (typically about 100 mg l-1) and variable, and that they contained about 65 mg g-1 of aluminium. The isotopic ratio 238Pu/239 + 240Pu, which can indicate the chronology of the discharge, was about 0.26, which suggested that the Sellafield discharges over at least 5 years contributed to the observed concentrations. The 239 + 240Pu and 241Am annual average concentrations in the particulate material were in the ranges 3.0-5.1 and 3.3-5.2 Bq g-1, respectively. The individual values were very variable in time, but highly correlated with each other. No significant downward trends in the concentrations could be identified over this period. This is consistent with the behaviour of a reservoir (the northeast Irish Sea) where Pu and Am, which are available for suspension in particulate material, are fed by the Sellafield discharges and are subject to a mean removal time of several years. Thus the effects of the large reduction in the Sellafield discharges which occurred over this period should only be observable over a longer time interval. The concentrations in the dissolved fractions in seawater were negligible compared with the particulate fraction concentrations, in sharp contrast with the situation in offshore seawater.(ABSTRACT TRUNCATED AT 250 WORDS)


Dracomyxa pallida gen. et sp. nov.: a new giant freshwater foraminifer, with remarks on the taxon Reticulomyxidae (emend.).
Reticulomyxids are organotrophic freshwater foraminifers typically placed within the radiation of early monothalamous Foraminifera. Though ubiquitous, reticulomyxids are rarely reported, which may be due both to their concealed life style and to inappropriate isolation techniques. Their taxonomic position is largely based on developmental stages of the life cycle. Here, we describe a new freshwater species, Dracomyxa pallida gen. nov. et sp. nov., isolated from submersed plant material. It has two possible life cycles including small cells, large plasmodia and encysted stages. Both types of development occur simultaneously in cultures derived from a single cell as well as in crude cultures. We amplified and sequenced a short sequence fragment of the 18S rRNA gene of the new isolate. Comparative phylogenetic analysis and molecular characterization indicate that it is a new reticulomyxid species, with Reticulomyxa filosa Nauss, Haplomyxa saranae Dellinger and Wobo gigas Hülsmann as the closest relatives. Unique features such as tripodal pediculated cysts and the lack of cleansing process justify the erection of a new genus.


Properdin and complement activation: a fresh perspective.
The C3 convertases are the major proteases of the complement cascade and are assembled at the site of complement activation via several different pathways. Properdin's functional role in stabilizing the alternative pathway convertase has been long established; however, new evidence demonstrates that properdin can also bind to certain microbial surfaces, and provide a platform for de novo convertase assembly. Therefore, properdin participates in two distinct mechanisms for complement activation: the alternative pathway and a properdin-directed pathway. Previous work had implicated the alternative pathway in the initiation and/or progression of several autoimmune diseases and in the host defense against certain bacterial pathogens. Those conclusions were based on evidence that cannot distinguish effects of the alternative pathway from effects of the properdin-directed pathway. With the identification of the new role for properdin in C3 convertase assembly there became a pressing need to reassess the mechanisms of complement activation, determine the specific role of properdin in each of these pathways, and explore the new therapeutic avenues that could arise.


Wound irrigation with tap water.
The study hypothesis was that irrigation with tap water is as efficacious as irrigation with sterile saline in removing bacteria from simple lacerations in preparation for wound closure. The study was conducted in a laboratory rat model previously described in the literature for evaluating wound irrigation techniques. The study used a randomized, blinded crossover design using 10 animals. Two full-thickness skin lacerations were made on each animal and each wound was inoculated with standardized concentrations of a Staphylococcus aureus broth. Wounds were irrigated for 4 minutes with normal saline from a syringe or 4 minutes with tap water from a faucet. Tissue specimens were sampled from each laceration prior to and following irrigation. Bacterial counts per gram of tissue were determined for each specimen and compared pre- and postirrigation. Preirrigation bacterial counts were not significantly different for saline vs tap water specimens. The wounds irrigated with saline had a mean reduction in bacterial count of 54.7% (SD=+/-28%), while the wounds irrigated with tap water had a mean reduction in bacterial count of 80.6% (SD=+/-20%) (p < 0.05, 2-tailed, paired t-test). In this animal model, bacterial decontamination of simple lacerations was not compromised, and was actually improved using tap water irrigation. This is most likely due to the mechanical differences in the types of irrigation. In certain instances, such as with upper-extremity lacerations, tap water irrigation would likely be cheaper and less labor-intensive than irrigation with normal saline from a syringe.


Differential diagnosis of choroidal neoplasms.
Experienced ophthalmologists who appropriately employ ancillary diagnostic testing, including fluorescein angiography, ocular ultrasonography, MRI, and fine needle aspiration biopsy, are remarkably accurate in the diagnosis of intraocular neoplasms. Recognizing the classic clinical features of the more commonly encountered lesions, such as choroidal melanoma, choroidal nevus, metastatic carcinoma to choroid, lymphoid tumors, and circumscribed choroidal hemangioma, and understanding the applicability and limitations of the various diagnostic tests are the keys to accurate detection.


[A1 and A2 blood group substances: are there structural differences?].
Blood group substances were extracted from erythrocytes of blood groups A1 and A2 and separated using HPTLC. Identification of blood group A was carried out on the chromatogramm using the PAP-technique. The specific demonstration of the serologically active glycosphingolipids allowed a comparison of the A1 and A2 blood group substance bands. The difference between the A1 and A2 Substances appears to be only a quantitative one.


A personal perspective on the needs of the weight loss surgery patient.
Weight loss surgery (WLS) patients, such as those undergoing bileopancreatic diversions and other Roux-en-Y gastric bypass procedures, present a relatively new population for the health care system. WLS creates special needs for this population that health care providers may not be fully aware of. The author, a former WLS patient and health care quality assurance professional, presents observations from his unique personal perspective. He feels that WLS patients, and post-WLS patients receiving other health care services, can be inadvertently jeopardized by the lack of awareness of their special needs. These needs are the result of the permanent postsurgical malnutrition and malabsorption syndrome occurring after the Roux-en-Y gastric bypass. These needs include nutrition, management of electrolytes during surgery, and pain management. Additionally, the morbidly obese patients may possess low self-esteem to the degree that they may not actively and appropriately participate in their own care. The author also offers personal observations concerning his belief that there is discrimination against morbidly obese patients in the health care setting. The author presents a personal case study as a tool for better understanding of the WLS patient by caregivers.


Structure-function studies of the human thyrotropin receptor. Inhibition of binding of labeled thyrotropin (TSH) by synthetic human TSH receptor peptides.
We have probed the hormone binding regions of the entire putative extracellular domain of the human thyrotropin (TSH) receptor (hTSHr) using synthetic peptides. A series of 26 overlapping peptides comprising the complete sequence of the extracellular domain of hTSHr was synthesized. Each peptide (20 amino acid residues each) was tested for its ability to interact with TSH, as evidenced by inhibition of binding of labeled hormone to native, membrane bound TSH receptors. Four of the 26 peptides interacted with labeled TSH and inhibited its binding to thyroid membranes. The most potent of these peptides was 256-275, which inhibited 125I-bovine TSH binding with an IC50 of 31.7 +/- 1.3 microM. The remaining peptides were 16-35 (351 +/- 9.4 microM), 106-125 (282 +/- 20.5 microM), and 226-245 (951 +/- 245 microM). An additional peptide, 286-305, showed minimal activity, and the remaining 21 peptides showed no activity. Peptides 256-275, 106-125, and 16-35 also inhibited binding of 125I-human chorionic gonadotropin to ovarian membrane receptors, suggesting that those regions of the receptor are involved in binding of a common glycoprotein hormone structure such as the alpha-subunit. In contrast, peptides 226-245 and 286-305 did not inhibit human chorionic gonadotropin binding, suggesting that these two regions are involved in hormone-specific activity. Of interest is the finding that the latter two peptides are from regions of TSHr that are largely dis-homologous to the lutropin receptor, whereas the former three, with the exception of 16-35, are from regions that are largely homologous between the two receptors. The data suggest that multiple, discontinuous regions of the extracellular domain of hTSHr are involved in the binding of the hormone. Furthermore, the binding regions are localized to TSHr-specific sequences as well as to regions that are highly homologous to LHr. This suggests that homologous regions of the two receptors are likely to perform similar functions in the interaction with their specific hormone, suggesting that those regions may be involved in binding of the glycoprotein hormone common alpha-subunit.


Interleukin 18 gene variation and risk of acute myocardial infarction.
Interleukin 18 is an important mediator of inflammation and has been associated with the development and aggravation of cardiovascular diseases. We report that common variation in the interleukin 18 gene is related to acute myocardial infarction, a frequent clinical manifestation of atherosclerosis and thrombosis in coronary arteries. In a population of European, mainly (90%) German, ancestry (2136 cases with acute myocardial infarction and 1211 controls), the association was based on specific alleles and haplotypes derived from a set of six tagging single nucleotide polymorphisms. The rs1946519-G (located in the 5' upstream region), rs360717-C (exon 1), rs5744241-G (intron 1), rs1834481-C (intron 3), and rs3882891-A (intron 5) alleles (P≤0.039) and a haplotype (GCGCAG haplotype; P=0.0028) containing the GCGCA motif derived from these alleles were associated with an increased risk of AMI. Corresponding with this result, the complementary alleles (rs1946519-T, rs360717-T, rs5744241-A, rs1834481-G, and rs3882891-C) and a haplotype (TTAGCG haplotype; P=0.018) with the TTAGC motif showed protective effects. Haplotypes not including the GCGCA or TTAGC motif were not related to AMI (P≥0.22). These observations suggest that the interleukin 18 gene is a susceptibility locus for acute myocardial infarction, a finding of potential interest in the clinical practice.


Long-term survival of patients with pN2 lung cancer according to the pattern of lymphatic spread.
N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned. The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S). All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8±48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients (p<0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p<0.001). Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients.


Optical transition probabilities in Er3+- and Tm3+-doped LiLa9(SiO4)6O2 crystals.
In this work, Er(3+) and Tm(3+)-doped LiLa(9)(SiO(4))(6)O(2) crystals have been grown from an Li(2)MoO(4) flux in the 1360-940 °C temperature range. Optical absorption spectra have been measured to obtain the experimental oscillator strengths of the transitions from the ground state to the excited levels. Judd-Ofelt calculations have been performed to estimate the Ω(2), Ω(4) and Ω(6) intensity parameters. The dynamics of selected Er(3+) and Tm(3+) manifolds have been investigated under selective pulsed excitation in order to determine the energy gap law by comparing the observed decay rates with the Judd-Ofelt predictions.


The molecular chaperone Hsp90 is required for high osmotic stress response in Saccharomyces cerevisiae.
Exposure of Saccharomyces cerevisiae to high osmotic stress evokes a number of adaptive changes that are necessary for its survival. These adaptive responses are mediated via multiple mitogen-activated protein kinase pathways, of which the high-osmolarity glycerol (HOG) pathway has been studied most extensively. Yeast strains that bear the hsp82T22I or hsp82G81S mutant alleles are osmosensitive. Interestingly, the osmosensitive phenotype is not due to inappropriate functioning of the HOG pathway, as Hog1p phosphorylation and downstream responses including glycerol accumulation are not affected. Rather, the hsp82 mutants display features that are characteristic for cell-wall mutants, i.e. resistance to Zymolyase and sensitivity to Calcofluor White. The osmosensitivity of the hsp82T22I or hsp82G81S strains is suppressed by over-expression of the Hsp90 co-chaperone Cdc37p but not by other co-chaperones. Hsp90 is shown to be required for proper adaptation to high osmolarity via a novel signal transduction pathway that operates parallel to the HOG pathway and requires Cdc37p.


Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin.
Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the influence of both duration and dose of metformin is unclear. Studies using holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We therefore investigated the prevalence of cobalamin deficiency in type 2 diabetes patients using both markers, and its relation with duration and dose of metformin use. This cross-sectional study among 550 type 2 diabetes patients using metformin (mean daily dose 1,306 mg; mean duration 64 months) was conducted in four primary care centers in Utrecht, the Netherlands. Cobalamin and holotranscobalamin concentrations were measured at the annual diabetes check. Detailed information on metformin use and confounding variables was collected from medical records. The prevalence of a cobalamin deficiency was 28.1 %, while a holotranscobalamin deficiency occurred in 3.9 % of the patients. Adjusting for multiple confounders, a 1 mg/day increase in daily metformin dose was associated (p < 0.001) with 0.042 (95 % CI -0.060, -0.023) decrease in cobalamin concentrations. Similarly, a 10 g increase of cumulative metformin dose was associated (p = 0.006) with -0.070 (-0.12, -0.021) lower cobalamin concentrations after adjustment for confounders. Duration of metformin use was not associated with cobalamin concentrations after multivariable adjustment. Similar results were observed for holotranscobalamin. Cobalamin deficiency occurs frequently among diabetes patients using metformin. A higher daily and cumulative doses of metformin were strongly associated with lower cobalamin and holotranscobalamin concentrations, while duration was not. It is thus important to account for metformin dose in recommendations for screening for cobalamin deficiency.


Invasive streptococcal infection of the periorbita and forehead.
Recent epidemiological reports suggest an increased frequency of invasive streptococcal infections linked to the appearance of a dominant group A Streptococcus serotype. Necrotizing streptococcal infections involving the skin and soft tissues of the face are uncommon. This case demonstrates the aggressive and invasive nature of these infections. The patient presented with symptoms of angioedema and was treated with corticosteroids. Her condition worsened and plastic surgery was consulted. There was extensive necrosis of the periorbital and forehead soft tissue, requiring extensive debridement to control the invasive process. Multiple reconstructive procedures were performed to close the defects and to preserve function of the facial muscles and eyelids. The literature indicates less than 50 reported cases of necrotizing streptococcal infections limited to the periorbita. This case reflects the importance of rapid diagnosis, and emphasizes the need for prompt and appropriate surgical treatment.


Differences between high- and low-angle subjects in arch form and anterior crowding from 23 to 33 years of age.
The aim of this study was to compare changes in arch width and length in high- and low-angle subjects. The material comprised the cephalograms and study models of 17 males and 15 females with a high-angle and 12 males and 16 low-angle females. The age of the subjects at the first examination (T1) was 22 years 10 months and 22 years 8 months in the high-angle groups, 22 years 5 months and 22 years 8 months in the low-angle subjects, respectively, for males and females. The second assessment (T2) was 10 years and 9 years 10 months later in the high-angle and, 10 years 3 months and 9 years 10 months in the low-angle groups, respectively. Statistical analysis of changes for each group during the observation period T1-T2 was undertaken using a paired t-test, and the differences between the groups with two-sample t-tests. The findings showed a general reduction in upper and lower arch length, an increase of intermolar width, and a decrease of intercanine width in both genders. Anterior perimeter and anterior space in both angles decreased in both males and females. The mean changes were small, but with large individual differences. There were no significant differences between the genders or the high- and low-angle groups in the changes, except that the female high-angle group had a statistically significant (P = 0.05) greater decrease in mandibular arch length than the low-angle female group.


Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party.
The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.


Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells.
The tumor microenvironment of human non-small cell lung cancer (NSCLC) is composed largely of stromal cells, including fibroblasts, yet these cells have been the focus of few studies. In this study, we established stromal cell cultures from primary NSCLC through isolation of adherent cells. Characterization of these cells by flow cytometry demonstrated a population which expressed a human fibroblast-specific 112-kDa surface molecule, Thy1, alpha-smooth muscle actin, and fibroblast activation protein, but failed to express CD45 and CD11b, a phenotype consistent with that of an activated myofibroblast. A subset of the tumor-associated fibroblasts (TAF) was found to express B7H1 (PD-L1) and B7DC (PD-L2) constitutively, and this expression was up-regulated by IFN-gamma. Production of cytokines and chemokines, including IFN-gamma, monokine induced by IFN-gamma, IFN-gamma-inducible protein-10, RANTES, and TGF-beta1 was also demonstrated in these cells. Together, these characteristics provide multiple opportunities for the TAF to influence cellular interactions within the tumor microenvironment. To evaluate the ability of TAF to modulate tumor-associated T cell (TAT) activation, we conducted coculture experiments between autologous TAF and TAT. In five of eight tumors, TAF elicited a contact-dependent enhancement of TAT activation, even in the presence of a TGF-beta1-mediated suppressive effect. In the three other tumors, TAF had a net suppressive effect upon TAT activation, and, in one of these cases, blockade of B7H1 or B7DC was able to completely abrogate the TAF-mediated suppression. We conclude that TAF in human NSCLC are functionally and phenotypically heterogeneous and provide multiple complex regulatory signals that have the potential to enhance or suppress TAT function in the tumor microenvironment.


Cellular internalization and intracellular biotransformation of silver nanoparticles in Chlamydomonas reinhardtii.
It is necessary to elucidate cellular internalization and intracellular biotransformation in order to accurately assess the toxicity and fate of nanoparticles after interaction with organisms. Therefore, this work employed a combination of high resolution imaging and in situ detection spectroscopic techniques to systematically investigate the intracellular localization, morphology and chemical speciation of silver in the cells of Chlamydomonas reinhardtii, a unicellular freshwater green alga, after exposure to AgNPs coated with polyvinylpyrrolidone at a concentration of 2.0 mg/L. High resolution secondary ion mass spectrometry and high-angle annular dark field scanning transmission electron microscopy together with energy dispersive spectroscopy and selected area electron diffraction collectively confirmed that after 48 h of exposure, AgNPs entered the periplasmic space after cellular internalization into the algal cells. Silver was also found to coexist with sulfur inside the cytoplasm in both crystalline and amorphous forms, which were further identified as β-Ag2S and silver thiolates with synchrotron X-ray absorption spectroscopy. In combination, these analyses demonstrated that silver inside algae could be attributed to the uptake and sequestration of Ag(+) ion released from AgNPs, which was further sequestrated into cellular compartments. This study provides solid evidence for particle internalization and biotransformation of AgNPs after interaction with algae.


Comparison of carbamazepine and lithium in the prophylaxis of bipolar disorders. A meta-analysis.
This meta-analysis assessed the equipotency of carbamazepine and lithium prophylaxis in bipolar disorder. We selected only randomised, double-blind, controlled studies comparing carbamazepine with lithium from a manual and computerised search, and subjected them to a quality inventory. Their statistical results were weighted by their quality score and combined. Four studies met our criteria, yielding, overall, P = 0.15. This result is not straightforward because the studies showed significant heterogeneity (P < 0.01). Differences in statistical power and sensitivity of outcome measure explain this heterogeneity and the conflicting results of the studies. Therefore, the prophylactic efficacy of carbamazepine remains questionable.


Obstetric and gynecologic ultrasound curriculum and competency assessment in residency training programs: consensus report.
Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multi-Society Task Force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency-assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at or close to 75% for each, and obtaining a set of five ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the Task Force expects that the criteria set forth in this document will evolve with time. The Task Force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency-assessment process. Incorporating this training curriculum and the competency-assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


The 5 lipoxygenase system in the vasculature: emerging role in health and disease.
Activation of the 5 lipoygenase (5LO) system within the vascular bed requires the presence of several cell types with distinct transcellular cross-talk mechanisms, resulting in the generation of 5LO produced metabolites and increased expression of receptors for these metabolites in vascular cells. The key products in this system, the leukotriens LTB4, LTC4 and LTD4, are potent mediators of vascular inflammation initiated by white blood cells and sustained or propagated thereafter through amplified metabolite generation and direct effects in endothelial and vascular smooth muscle cells. Leukotrienes act to enhance cell permeability and increase oxidative stress, vascular smooth muscle cell migration and arterial tone. 5LO activation is highly regulated, and is apparently both model/species-specific and region-specific. 5LO activation is also linked to plaque progression, plaque stability, activation of matrix metalloproteinases, propensity to coronary and cerebrovascular events and the evolution of aortic aneurysms. Genetic variants in the 5LO activating protein are strongly linked to increased cardiovascular risk and may serve as useful markers for future therapy targeting down regulation of 5LO expression and activity as a means to combat cardiovascular disease.


Environmental fluctuations facilitate species co-existence and increase decomposition in communities of wood decay fungi.
A fluctuating environment may facilitate co-existence of species, and high species richness may be important for maintaining ecosystem processes under changing environmental conditions. A positive relationship has been found between species richness and primary production in many experiments, and there is now an increasing interest whether similar relationships also apply to microorganisms and decomposition. Basidiomycete fungi are the primary decomposers of wood with the functional groups brown and white rot fungi, which differ with respect to decay strategy. In this study, 16 species of boreal wood decay fungi, 8 brown rot fungi and 8 white rot fungi, were assembled in artificial communities. The aims were to study species persistence, wood decomposition and metabolic efficiency in fungal communities of increasing levels of species richness under constant and fluctuating temperature regimes. Species persistence was generally low, but temperature fluctuations facilitated co-existence of species. Decomposition was highest at intermediate diversity levels under the fluctuating temperature regime. Metabolic efficiency, estimated as the amount of fungal mycelium formed per amount of degraded wood, decreased with increasing community complexity under the fluctuating temperature regime. Brown and white rot fungi differed in decomposition rates and metabolic efficiency, but no synergistic effects were found where the two functional groups were mixed. This study demonstrates how niche differentiation in a variable environment may act to maintain diversity and function. In our experiment, differences in functional responses to the varying temperature rather than resource partitioning between brown and white rot fungi had significant effects. Niche differentiation is likely to be particularly important in maintaining species diversity in communities of wood decaying fungi, which are known from previous studies to be characterised by intense competition, and where otherwise metabolically costly interactions lead to species exclusion and dominance by highly competitive species.


Weak synchronization and large-scale collective oscillation in dense bacterial suspensions.
Collective oscillatory behaviour is ubiquitous in nature, having a vital role in many biological processes from embryogenesis and organ development to pace-making in neuron networks. Elucidating the mechanisms that give rise to synchronization is essential to the understanding of biological self-organization. Collective oscillations in biological multicellular systems often arise from long-range coupling mediated by diffusive chemicals, by electrochemical mechanisms, or by biomechanical interaction between cells and their physical environment. In these examples, the phase of some oscillatory intracellular degree of freedom is synchronized. Here, in contrast, we report the discovery of a weak synchronization mechanism that does not require long-range coupling or inherent oscillation of individual cells. We find that millions of motile cells in dense bacterial suspensions can self-organize into highly robust collective oscillatory motion, while individual cells move in an erratic manner, without obvious periodic motion but with frequent, abrupt and random directional changes. So erratic are individual trajectories that uncovering the collective oscillations of our micrometre-sized cells requires individual velocities to be averaged over tens or hundreds of micrometres. On such large scales, the oscillations appear to be in phase and the mean position of cells typically describes a regular elliptic trajectory. We found that the phase of the oscillations is organized into a centimetre-scale travelling wave. We present a model of noisy self-propelled particles with strictly local interactions that accounts faithfully for our observations, suggesting that self-organized collective oscillatory motion results from spontaneous chiral and rotational symmetry breaking. These findings reveal a previously unseen type of long-range order in active matter systems (those in which energy is spent locally to produce non-random motion). This mechanism of collective oscillation may inspire new strategies to control the self-organization of active matter and swarming robots.


Type III effector proteins: doppelgangers of bacterial virulence.
Bacterial pathogens have co-evolved with their hosts in their ongoing quest for advantage in the resulting interaction. These intimate associations have resulted in remarkable adaptations of prokaryotic virulence proteins and their eukaryotic molecular targets. An important strategy used by microbial pathogens of animals to manipulate host cellular functions is structural mimicry of eukaryotic proteins. Recent evidence demonstrates that plant pathogens also use structural mimicry of host factors as a virulence strategy. Nearly all virulence proteins from phytopathogenic bacteria have eluded functional annotation on the basis of primary amino-acid sequence. Recent efforts to determine their three-dimensional structures are, however, revealing important clues about the mechanisms of bacterial virulence in plants.


Daytime sleepiness in young adults.
The daytime sleepiness of a large sample (n = 129) of healthy, young (age 18-29) adults with no sleep-wake complaints was measured and compared with that of a sample (n = 47) of older (age 30-80) healthy, normal sleeping, subjects. Each spent 8 h in the laboratory on 1 night and received the Multiple Sleep Latency Test (MSLT) the following day. Sleep latency was measured at 1000, 1200, 1400, and 1600 h. Mean sleep latency ranged from 2 to 20 min within each group, but the shape of the distribution of latency between groups was different. The mean latency of young subjects (particularly college students) was shorter than that of the older subjects, with the differences occurring between the sleepiest 80% of each distribution. Among the college students, those with higher nocturnal sleep efficiencies (the previous night) were sleepier the following day than those with lower sleep efficiencies. The relation between nocturnal sleep efficiency and daytime sleepiness suggests that the increased sleepiness of average young adults is due to mild sleep restriction.


Membrane vesicle formation due to acquired mitoxantrone resistance in human gastric carcinoma cell line EPG85-257.
A newly established gastric carcinoma cell line (EPG85-257P) exhibited a high sensitivity to mitoxantrone (DHAD) as determined by a monolayer proliferation assay. The concentration to inhibit cell growth to 50% of controls (IC50) was 0.0022 micrograms/ml culture medium. The cells were continuously incubated for more than 4 months in the presence of stepwise increased concentrations of DHAD, and the IC50 was increased to 0.41 micrograms/ml, i.e., 186.4-fold. This resistant variant was named EPG85-257RNOV. The EPG85-257RNOV cells became cross-resistant to Adriamycin with enhanced IC50 by 10.5-fold and to daunomycin with enhanced IC50 by 3.9-fold. No distinct resistance was observed to vinblastine, vincristine, and colchicine. Verapamil (10(-6), 4 X 10(-6) and 10(-5) M) and cyclosporin A (10(-6), 3 X 10(-6) and 10(-5) M) did not reverse DHAD resistance. As shown by immunocytochemistry (monoclonal antibodies: C219 and JSB-1) and Northern blot analysis, DHAD resistance was not associated with the appearance of the multidrug resistance (MDR)-associated (Mr 170,000) P-glycoprotein or the overexpression of P-glycoprotein mRNA. The data indicate a chemoresistance pattern unlike typical MDR (often called "atypical" MDR). The phenotypes of parent and resistant EPG85-257 cells were compared using interference contrast microscopy, electron microscopy, and immunocytochemistry. After DHAD application the following structural characteristics were found to be associated with emergence of resistance: (a) intensive formation of surface vesicles in the resistant variant. Such vesicles were almost absent in sensitive cells; (b) the vesicles contained the selecting DHAD which was visualized by its blue color; and (c) in electron microscopy the vesicles were formed by an inner and an outer double membrane, presumably derived from the plasmalemma. These observations suggest a complex cellular mechanism responsible for DHAD resistance which includes formation of membrane vesicles, vesicular drug binding, and drug compartmentalization.


Superficial fungal infections seen at a tertiary health centre: clinical and mycological studies.
Superficial fungal infections are common in the tropics, partly due to the climate, relatively poor hygiene, and lifestyle of the people. To determine the clinical forms and aetiological agents of superficial fungal infections as seen among skin cases in the north- central part of Nigeria. All consecutive new patients seen at the skin clinic of the General Out-patient Department of the Federal Medical Centre, Bida from July 2006 to December 2007 were included in this prospective study. Participants were examined for superficial fungal lesions. Samples of skin scrapings for microbiological investigations were obtained from suspicious lesions. A total of 381 patients attended the Skin Clinic during the period of study. Superficial fungal infections constituted 89(23.4%) of all skin cases seen. The commonest clinical type of fungal infection was Tinea corporis, followed by Tinea unguium. Male to female ratio of clinical lesions was 1: 1.5. A total of 41 samples grew fungal organisms on Sabouraud Dextrose Agar culture, of which dermatophytes were the isolates in 22(53.7%), while non-dermatophytes accounted for the rest. Seven species of dermatophytes, dominated by Trichophyton spp. 15 (68.2%), followed by Microsporum gypseum 4(18.2%), and Epidermophyton floccosum 3(13.6%) were the main isolates. The most commonly recovered species were T. mentagrophytes (36.4%). These data show the continued predominance of dermatophytes as the principal pathogen in superficial fungal infection. Trichophyton spp. is the predominant class of which T. mentagrophyte is the most prevalent.


Delayed therapy of experimental ischemia with competitive N-methyl-D-aspartate antagonists in rabbits.
N-methyl-D-aspartate antagonists are effective in limiting ischemic damage to the brain and spinal cord if treatment is begun at time of ischemic injury. More clinically relevant delayed therapy has not been adequately investigated. We report the temporal profile of efficacy for two competitive N-methyl-D-aspartate antagonists in therapy of central nervous system ischemia. CGS-19755 (30 mg/kg) or LY233053 (100 mg/kg) was administered 5, 30, or 60 minutes after reversible spinal cord ischemia in rabbits, induced by temporary occlusion of the infrarenal aorta. Duration of occlusion for individual animals was varied to provide a range of ischemia for each experimental group. The P50 represents the duration (in minutes) associated with a 50% probability of resultant permanent paraplegia. Neuroprotection is demonstrated if a drug prolongs the P50. CGS-19755 significantly prolonged the P50 (t test, P = .003) when given 5 minutes after ischemia, but not if delayed by 30 or 60 minutes (P50: control, 24.1; 5 minutes, 31.4; 30 minutes, 30.1; 60 minutes, 26.6). LY233053 was efficacious at 5 (P = .0008) and 30 (P = .002) minutes, but not at 60 minutes (P50: control, 26.8; 5 minutes, 39.4; 30 minutes, 36.0; 60 minutes, 25.6). These competitive N-methyl-D-aspartate antagonists are effective in limiting ischemic damage, but protection is lost if therapy is not initiated within 60 minutes of injury.


Pregnancy among Hispanic teenagers: is good parental communication a deterrent?
Effective communication between Hispanic parents and teens about sexual issues may deter adolescent pregnancy, yet little is known about the prevalence or impact of such communication. The study examined this potential relationship in a cohort of urban Hispanic adolescents. A questionnaire was administered to a non-random sample of pregnant and non-pregnant Hispanic women aged 12-18 years attending inner city schools in Los Angeles to obtain demographic, sexual activity and communication information. Logistic regression analysis was used to evaluate the independent contribution of risk factors to teenage pregnancy. Good communication with one's mother was inversely related to pregnancy; the adjusted odds ratio of pregnancy if the mother told the daughter about sex was 0.3 (95% CI 0.2-0.6). Friends' love was also inversely related to pregnancy (odds ratio 0.7; 95% CI 0.6-0.8). In order of increasing strength, alcohol and drug use, favorable attitude toward premarital sex, receipt of welfare, older age at menarche, and older age were all significantly related to pregnancy. Pregnant Hispanic teenagers have poorer communication with their parents than do other Hispanic teens. Efforts to reduce the incidence of adolescent pregnancy among Hispanics may need to address not only family communication but also issues outside the home such as alcohol and recreational drugs.


Forensic application of epidermal AQP3 expression to determination of wound vitality in human compressed neck skin.
In forensic practices, it is often difficult to determine wound vitality in compression marks of the neck with naked eyes. AQP1 and AQP3 are the major water channels associated with skin. Thus, we immunohistochemically examined the expression of AQP1 and AQP3 in neck skin samples to discuss their forensic applicability to determination of the wound vitality. Skin samples were obtained from 56 neck compression cases (hanging, 35 cases; strangulation, 21 cases). The intact skin from the same individual was taken as a control. Although AQP1 was immnunostained in dermal capillaries in both the neck compression marks and intact skin samples, there was no significant difference in the magnitude of AQP1 expression between both groups. On the contrary, AQP3-positive signals could be faintly detected in uninjured skin samples, and the positive signals seemed more intense in the keratinocytes in compression regions. Morphometrical analyses revealed that the ratio of AQP3-expressed keratinocytes was significantly enhanced in neck compression regions, compared with control groups. From the viewpoints of forensic pathology, immunohistochemical detection of AQP3 in the neck skin can be considered a valuable marker to diagnose the trace of antemortem compression.


[Pharmacodynamic study of myocardial contraction using ultrasonic echography during isoproterenol perfusion in the normal subject].
An echographic study, both before and under isoproterenol infusion, was performed on 50 normal subjects. The movements of the posterior wass of the left ventricle were found to be averagely increased of 62% as regards the amplitude, 114% for the mean speed and 124% for the maximum speed of contraction. The transcerse diameter of the left ventricular cavity decreased by 5.25%. The circumferential fibres shortening speed expressed in circumference by second increased by 128%. An uninvasive method, echography, as cineangiography, makes it possible to assess the myocardial contractility on the basis of measurement of the average speed of circumferential fibres and of the diameter of the left ventricle.


Isolated parotid acinar cells from DL-isoproterenol-treated rats. A cellular model for cystic fibrosis.
The morphology and composition of isolated acinar cells from the enlarged parotid glands of rats treated chronically with DL-isoproterenol were investigated and compared with isolated acinar cells from parotids of control untreated rats. Changes similar to those observed in parotid acinar cells from patients with cystic fibrosis were demonstrated.


Kinin B2 receptor deletion and blockage ameliorates cisplatin-induced acute renal injury.
Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1β and TNF-α). The kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy.


Stressful intensive care unit medical crises: How individual responses impact on team performance.
Intensive care units (ICUs) are recognized as stressful environments. However, the conditions in which stressors may affect health professionals' performance and well-being and the conditions that potentially lead to impaired performance and staff psychological distress are not well understood. The purpose of this study was to determine healthcare professionals' perceptions regarding the factors that lead to stress responses and performance impairments during ICU medical crises. A qualitative study in a university-affiliated ICU in Canada. We conducted 32 individual semistructured interviews of ICU nurses, staff physicians, residents, and respiratory therapists in a university-affiliated hospital. The transcripts of the audiotaped interviews were analyzed using an inductive thematic methodology. Increased workload, high stakes, and heavy weight of responsibility were recognized as common stressors during ICU crises. However, a high level of individual and team resources available to face such demands was also reported. When the patient's condition was changing or deteriorating unpredictably or when the expected resources were unavailable, crises were assessed by some team members as threatening, leading to individual distress. Once manifested, this emotional distress was strongly contagious to other team members. The ensuing collective anxiety was perceived as disruptive for teamwork and deleterious for individual and collective performance. Individual distress reactions to ICU crises occurred in the presence of unexpectedly high demands unmatched by appropriate resources and were contagious among other team members. Given the high uncertainty surrounding many ICU medical crises, strategies aimed at preventing distress contagion among ICU health professionals may improve team performance and individual well-being.


A new examination method for detecting renovascular hypertension: functional DTPA renal scintigraphy sensitized by captopril.
DTPA functional renal camera scintigraphy (DTPA-FS) was performed in 220 patients with moderately severe and severe hypertension after an initial 7-14-day Captopril + thiazide-type diuretic treatment. If, comparing it with the DTPA-FS prior to treatment, appearance or increase of a side difference were observed and it was also indicated by the clinical picture, nephroangiography was performed. Using this method, 15 cases of unilateral, 3 bilateral renal arterial stenoses were recognized, and in one case restenosis was diagnosed, in all cases of positive DTPA-FS with Captopril. In negative case of DTPA-FS sensitized with Captopril, there was no positive angiographic finding. The method of DTPA-FS performed under Captopril effect is considered to be a simple, harmless, specific out-patient examination for screening genuine renovascular hypertension. To perform several angiographies likely to be negative can be avoided by this method. The hypotensive effect of Captopril may, at the same time, be a useful guide in differentiating patients with renovascular hypertension being suitable most of all for surgical intervention or angioplasty.


Cognitive impairment associated with chemotherapy for cancer: report of a workshop.
Cognitive dysfunction may occur in some patients who receive chemotherapy. We provide a summary of an April 2003 workshop on this topic, that included medical oncologists, radiologists, clinical and experimental psychologists, and patient advocates. Current studies indicate that cognitive deficits are often subtle, although they are observed consistently in a proportion of patients, may be durable, and can be disabling. Deficits have been observed in a range of cognitive functions. Underlying mechanisms are unknown, although preliminary studies suggest there may be genetic predisposition and that cognitive impairment may be accompanied by changes in the brain detectable by neuroimaging. The following priorities were established for future research: (1) large-scale clinical studies that use both a longitudinal design and concurrent evaluation of patients with cancer who do not receive chemotherapy-such studies should address the probability and magnitude of cognitive deficits, factors that predict them, and underlying mechanisms; (2) exploration of discrepancies between subjective reports of cognitive dysfunction and the objective results of cognitive testing; (3) studies of cognitive function in patients receiving treatment for diseases other than breast cancer, and in both men and women, to address the hypothesis that underlying mechanisms relate to changes in serum levels of sex hormones and/or to chemotherapy-induced menopause; (4) development of interventions to alleviate these problems; and (5) development of animal models and the use of imaging techniques to address mechanisms that might cause cognitive impairment associated with chemotherapy.


Fatal Cardiac Arrest in 2 Children: Possible Role of Ondansetron.
Ondansetron is commonly used to treat vomiting in gastroenteritis, but has a United States Food and Drug Administration black box warning for risk of Q wave to T wave time interval (QT) prolongation. We report 2 pediatric cases of fatal refractory cardiac arrest after administration of ondansetron. A 10-year-old previously healthy boy presented to the emergency room with gastroenteritis symptoms. After intravenous fluids, morphine, antibiotics, and 2 doses of ondansetron, the patient became unresponsive with agonal respirations and a wide complex tachycardia consistent with ventricular tachycardia. In a second case, an 86-day-old infant with previously unidentified congenital cardiomyopathy presented to our emergency department with gastroenteritis symptoms. The patient received ondansetron and subsequently experienced repeated bouts of supraventricular tachycardia which progressed to ventricular fibrillation. Resuscitation efforts failed in each case, and both patients expired. Ondansetron can cause dose-dependent QT prolongation effects, which are more clinically relevant when other proarrhythmic elements are present. There is very limited published experience on use of ondansetron in children younger than 2 years. Our 2 cases join 2 previous case reports of death after ondansetron administration for gastroenteritis. The pharmacology of ondansetron's cardiac effects and drug-induced QT prolongation is discussed. Patients may have hidden risk factors that, together with ondansetron, could result in a proarrhythmic state that could lead to adverse effects, such as arrhythmias. Administration of ondansetron should be individualized and used cautiously in patients with risk factors for arrhythmia.


Molecular identification of Corni Fructus and its adulterants by ITS/ITS2 sequences.
The DNA barcoding method was used to accurately and rapidly identify Corni Fructus and its adulterants. Genomic DNA extracted from Corni Fructus and its adulterants were used as templates. The ITS (internal trascribed spacer) regions were amplified using polymerase chain reaction. Sequence assembly was performed using CodonCode Aligner V 3.5.4. Genetic distances were computed using MEGA V 5.0. Species identification was conducted using neighbor-joining (NJ) trees. The ITS sequence length of Corni Fructus was 659 bp. The average intra-specific genetic distance of Corni Fructus was 0.005, markedly lower than the inter-specific genetic distance between Corni Fructus and its adulterants (0.357). The ITS2 sequence length of Corni Fructus was 250 bp. No variation was found among the different samples. The interspecific genetic distance of ITS2 between Corni Fructus and its adulterants was 0.571. NJ trees and BLAST results indicated that Corni Fructus and its adulterants can be easily differentiated with monophyly. ITS/ITS2 regions can accurately and efficiently distinguish Corni Fructus and its adulterants. In addition, the results not only established the foundation for the clinical safety in the utilization of Corni Fructus, but also provided reference for molecular identification of other Chinese herbal medicine and Chinese herbal pieces.


Testing theoretical explanations of mammography use.
The theory of care-seeking behavior was tested in the context of mammography use among midwestern women (N = 178). In multivariate logistic regressions, mammography adherence in the past 5 years was related to habit, the interaction of anxiety and barriers, belief in one's risk of breast cancer, age, and family history of breast cancer. Recent use of mammograms (i.e., in the past 1 or 2 years, depending on age) was related to norm and habit. Intention was related to utility beliefs regarding mammography, norm, habit, and belief in one's risk of breast cancer. As proposed from theory, anxiety and barriers interacted to influence adherence, the variables of habit, utility beliefs, and norm were related to either recent use or intention. Contrary to theory, belief in one's risk of breast cancer, age, and family history of breast cancer were related to adherence or intention after controlling for theoretically derived variables. The explanatory variables for each outcome were not identical, indicating that these mammography-related outcomes are characteristically different.


Intermediate to highly suspicious calcification in breast lesions: a radio-pathologic correlation.
Breast calcification is an important feature in the radiological assessment of breast lesions. There are well established diagnostic criteria basing on the morphology and distribution of the calcifications radiologically with recommendation protocols. Pathologically, calcifications in breast lesions are of dystrophic type, and may occur in either the secretory materials or necrotic debris, with inflammation and osteopontin being plausible mediators. Detection of calcium phosphate (hydroyapaptite) is considerably easier than calcium oxalate. Radiologically amorphous calcification represents a borderline type of calcification, and occurs in both benign and malignant (low grade) lesions, and warrants careful follow up and investigation. Clustering of calcification alone may not be an accurate predictor for malignancy, but when there are associated features like pleomorphism, branching, architectural distortion, and associated mass or density, the predictive value for malignant increases. Adequate sampling of calcification in the biopsy is crucial in the management of patients; in general, needle core biopsy or mammotome biopsy achieve satisfactory calcification retrieval. In a benign biopsy that fails to identify the calcifications visible in the mammography, further evaluation or cutting of the histologic block is recommended to minimize the potential of a false negative investigation.


The future of B-cell lymphoma therapy: the B-cell receptor and its downstream pathways.
It is becoming increasingly apparent that tonic signaling through the B cell receptor provides a growth and survival signal in many types of B cell lymphomas, and that disruption of B cell receptor signaling can be lethal to malignant B cells. Several small molecule tyrosine kinase inhibitors, which block signaling pathways downstream from the B cell receptor, are in active clinical development. Preliminary data suggests impressive activity in relapsed and refractory B cell lymphomas. Among the kinases which have been targeted are Spleen tyrosine kinase (Syk), the Bruton's tyrosine kinase (BTK), and phosphoinositide 3-kinase (PI3K). This article discusses the rationale for targeting these pathways and summarizes the current clinical trial data for agents targeting Syk, BTK, and PI3K.


Levels and correlates of awareness of tobacco promotional activities among adult smokers in Malaysia and Thailand: findings from the International Tobacco Control Southeast Asia (ITC-SEA) Survey.
To examine the impact of tobacco advertising policy on adult smokers' awareness of tobacco promotion in two developing countries--Malaysia and Thailand. Data from 2004 Malaysian and 2000 Thai adult smokers who participated in the baseline wave of the International Tobacco Control Southeast Asia survey (ITC-SEA). Respondents were asked in a face-to-face interview conducted between January and March 2005 to indicate their levels of awareness of tobacco advertising and promotional activities in the last six months. Unprompted awareness of any tobacco marketing activities was very low in Thailand (20%) but significantly higher in Malaysia (53%; OR = 5.6, 95% CI: 3.5 to 8.9, p<0.001). When prompted about specific locations, Thai adult smokers reported very low recall of tobacco advertising where it was banned, being highest around point of sale, particularly street vendors (7.5%). In contrast, Malaysian adult smokers reported significantly higher levels of awareness of tobacco advertising in all locations (range = 17.7% noticing in disco lounges to 59.3% on posters) including where they are notionally banned (for example, billboards). These findings demonstrate that comprehensive tobacco advertising legislation when well implemented can lead to dramatic decline in awareness of tobacco promotion, thus supporting strong implementation of Article 13 of the Framework Convention on Tobacco Control.


A histochemical demonstration of altered cytochrome oxidase activity in the rat brain by neuroleptics.
Regional alterations in neuronal functional activity were examined in the rat brain using cytochrome-c oxidase (COX) histochemistry following chronic neuroleptic treatment. Haloperidol, fluphenazine, and clozapine were administered to animals for 28 days after which profiles of COX activity were generated. Significant increases in COX activity were evident in area 2 of the frontal cortex of all treated animals. Clozapine and fluphenazine, but not haloperidol, caused significant increases in COX activity in the caudate nucleus, nucleus accumbens, septum, and pontine nucleus. Statistically significant increases in COX activity were also observed in hippocampal CA2 and CA3 subfields in clozapine treated animals. Results offer support for the concept that neuroleptics achieve their therapeutic effects primarily via an enhancement of brain function in the frontal cortex, but also point to other brain regions which may be involved in the actions of these drugs.


Effects of tail amputation and treatment with an albendazole controlled-release capsule on the health and productivity of prime lambs.
To assess the effects of tail amputation and treatment with albendazole controlled-release capsule (CRC) on the health and productivity of prime lambs. Field trials on three farms. About 551 Coopworth-Poll Dorset cross, 588 Border Leicester-Merino-Poll Dorset cross and 575 Corriedale-Poll Dorset cross lambs. On three farms, lambs with amputated tails were compared with an equal number of lambs with tails left entire. In both of these groups half the lambs were treated with an albendazole CRC 13 weeks after the start of lambing. Faecal soiling of the breech and flystrike of the breech were recorded. Lambs were weighed and body condition scored at each visit and carcase weights and fat score of each lamb at slaughter. Procedures on the slaughter chain were monitored to determine whether the retention of the tail caused any problems. There were no observed benefits of treatment with an albendazole CRC on the farms in the study. There was no strong evidence that tail amputation had any long-term effect on the growth rate of lambs or carcase traits. No detrimental effects were observed during processing of lambs with long tails in the abattoir. Lambs with entire tails had significantly greater mean dag scores than lambs with amputated tails. On one farm lambs with entire tails were at about twice the risk of requiring crutching and on another farm were at three times the risk of breech strike compared with lambs with amputated tails. This study provides evidence that amputating the tail is not an absolute requirement to maintain the health and welfare of prime lambs, but leaving the tail of prime lambs entire is likely to increase chemical usage to control flystrike, and to increase the frequency of crutching.


Association between social support, functional status, and change in health-related quality of life and changes in anxiety and depression in colorectal cancer patients.
The aim of this study was to explore the association between baseline social support, functional status, and change in health-related quality of life (HRQoL) in colorectal cancer patients and change in anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS) at 1 year after surgery. Consecutive patients who were due to undergo therapeutic surgery for the first time for colon or rectal cancer in 9 hospitals in Spain were eligible for the study. Patients completed the following questionnaires before surgery and 12 months afterward: 1 HRQoL instrument, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire; a social support questionnaire, the Duke-UNC Functional Social Support Questionnaire; the Barthel Index, to assess functional status; the HADS, to assess anxiety and depression; and questions about sociodemographic information. General linear models were built to explore the association between social support, functional status, and change in HRQoL and changes in anxiety and depression 12 months after surgery. A total of 947 colorectal cancer patients took part in the study. Patients' functional status, social support, and change in HRQoL were associated with changes in anxiety and depression. Greater social support and improvements in physical, cognitive, and social functioning and in insomnia resulted in improvements in anxiety and depression. No functionally independent patients were associated with lesser improvements in anxiety and depression. Colorectal cancer patients who have more social support, are functionally independent and have higher improvements in HRQoL may have better results in anxiety and depression at 1 year after surgery, adjusting for age, gender, location, occupation, and baseline HADS scores.


Optimising pre- and postoperative imaging for thoracic aortic pathology.
Thoracic aortic pathology carries significant morbidity and mortality, which requires prompt and accurate clinical and radiological evaluation. Advances in imaging technologies have improved our knowledge of the mechanisms of growth and rupture and our understanding of endovascular repair. Computed tomography has become a crucial component in this process, replacing catheter-based angiography as the most commonly used pre- and postoperative imaging modality for the thoracic aorta. Functional imaging methods such as magnetic resonance and echocardiography are evolving and are able to provide the clinically relevant anatomic, haemodynamic and biomechanical information that is necessary for accurate diagnosis, risk stratification and selection of the appropriate treatment for an individual patient. The availability of advanced image acquisition expertise and equipment is spreading to a growing number of institutions worldwide and will greatly enhance existing imaging strategies for patients with thoracic aortic pathology.


Can the benefits of rtPA treatment for stroke be improved?
Tissue-type plasminogen activator (tPA) is a serine protease well known to promote fibrinolysis. This is why: its recombinant form (rtPA) can be used, either alone or combined with thrombectomy, to promote recanalization/reperfusion following ischemic stroke. However, its overall benefits are counteracted by some of its side-effects, including incomplete lysis of clots, an increased risk of hemorrhagic transformation and the possibility of neurotoxicity. Nevertheless, better understanding of the mechanisms by which tPA influences brain function and promotes its alteration may help in the design of new strategies to improve stroke therapy.


Accumulation of persistent organic pollutants in parasites.
Organisms are simultaneously exposed to various stressors, including parasites and pollutants, that may interact with each other. Research on the accumulation of organic compounds in host-parasite systems is scant compared to studies on parasite-metal interactions and mainly focuses on intestinal endoparasites. We reviewed factors that determine the accumulation of persistent organic pollutants (POPs) in host-parasite systems. The wet/dry weight-based concentration of POPs in these parasites is usually lower than that in host tissues because of lower lipid contents in the parasites. However, the fractionation of the pollutants into parasites and their hosts may vary, depending on developmental stages in the life cycle of the parasites. Developmental stages determine the trophic relationship and the taxon of the parasite in the host-parasite systems because of different feeding strategies between the stages. Lipid-corrected concentrations of organic chemicals in the host are usually higher than those in the endoparasites studied. This phenomenon is attributed to a number of physiological and behavioural processes, such as feeding selectivity and strategy and excretion. Moreover, no significant relationship was found between the accumulation factor (i.e. the ratio between the lipid-corrected concentrations in parasites and in their hosts) for polychlorinated biphenyls and either hydrophobicity or molecular size. At the intermediate hydrophobicity, larger and more lipophilic compounds are accumulated at higher levels in both parasites and the host than smaller and less lipophilic compounds. The bioaccumulation of POPs in parasites is affected by some other abiotic, e.g. temperature, and biotic factors, e.g. the number of host species infected by parasites.