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Quality assurance of item writing: during the introduction of multiple choice questions in medicine for high stakes examinations.
One Norwegian medical school introduced A-type MCQs (best one of five) to replace more traditional assessment formats (e.g. essays) in an undergraduate medical curriculum. Quality assurance criteria were introduced to measure the success of the intervention. Data collection from the first four year-end examinations included item analysis, frequency of item writing flaws (IWF) and proportion of items testing at a higher cognitive level (K2). All examinations were reviewed before after delivery and no items were removed. Overall pass rates were similar to previous cohorts examined with traditional assessment formats. Across 389 items, the proportion of items with >or=5% of candidates marking two or more functioning distracters was >or=47.5%. Removal of items with high p-values (>or=85%), this item distracter proportion became >75%. With each successive year in the curriculum the proportion of K2 items used rose steadily to almost 50%. 31/389 (7%) items had IWFs. 65% items had a discriminatory power, >or=0.15. Five item quality criteria are recommended: (1) adherence to an in-house style, (2) item proportion testing at K2 level, (3) functioning distracter proportion, (4) overall discrimination ratio and (5) IWF frequency.
18,825,568
Associations between social capital and health status in an Australian population.
This study investigated the association between social capital and health related quality of life in a sample of Australian adults. Information was collected from a sample of adults in Queensland, Australia relating to health status, health related quality of life and related social determinants of health by computer-assisted-telephone-interview survey. Significant associations were observed between social capital and physical health when adjusting for selected demographic measures. No significant association was observed between social capital and mental health. The research produced equivocal results regarding the associations between social capital and the selected measures of health-related quality of life. Evidence is presented in support of the association between social capital and physical health status, whereas no associations were observed between mental health status and social capital. The role and relationship between health and social capital remains elusive. More work is required to clearly support social capital's role in physical and mental health and well-being.
18,825,585
Predictors of fatigue over 1 year among people with rheumatoid arthritis.
Fatigue is a systemic feeling of exhaustion that is a common symptom of many chronic illnesses, including the autoimmune inflammatory disease rheumatoid arthritis (RA). We examined predictors of levels of fatigue among people with RA using Leventhal's Common-Sense Model (CSM), which states that cognitive representations of an illness spur (or halt) people's efforts to cope and thereby influence outcomes of the illness. Our use of the CSM was designed in the light of evidence in the literature specific to fatigue in RA. Current fatigue was reported on a 100 mm visual analogue scale (with anchors "No fatigue" and "Unbearable fatigue") by 114 people (73.7% women) with RA at baseline and 1 year later. Baseline employment status, pain, impact of disability, sleep disruption frequency, depressed mood, perceptions of consequences, arthritis self-efficacy and attempts to cope by praying/hoping were also self-reported. Duration of RA and a haematological measure of systemic inflammation (erythrocyte sedimentation rate; ESR) were obtained from hospital records. Unexpectedly, RA duration did not predict fatigue after 1 year, although lower baseline inflammation did (controlling for baseline fatigue and other disease impact variables). This may be due to sampling flares of RA at baseline. Baseline perceptions that RA has severe consequences and is uncontrollable also predicted greater fatigue after 1 year but this relationship was not mediated by praying/hoping. Targeted psychological care to modify perceptions of severe consequences may therefore improve later fatigue for people with RA even when the condition is longstanding, but the mechanisms of any benefit require further investigation.
18,825,587
Diversity of mucosa-associated microbiota in active and inactive ulcerative colitis.
Recent findings indicate that bacteria play an important role in the pathogenesis of inflammatory bowel disease (IBD). However, the exact role of bacteria in ulcerative colitis (UC) has still to be elucidated. The objective of the study was to investigate the potential differences in the intestinal microbiota between patients with UC and control subjects, using terminal restriction fragment length polymorphism (T-RFLP) analysis of the mucosa-associated microbiota from UC patients and non-IBD controls. Nine active UC patients and 11 non-IBD controls were included in the study. Seven patients with active UC who entered into the inactive phase after antibiotic combination treatment were also classified as patients with inactive UC. Mucosa-associated microbiota was compared between non-IBD controls and UC patients using T-RFLP analysis. Microbiota in both the active and inactive phase was also analyzed in UC patients receiving antibiotic treatment. T-RFLP patterns of mucosa-associated microbiota differed between active UC patients and non-IBD controls. Microbial compositions of active UC patients were significantly less diverse. The difference resulted from loss of commensals. From the viewpoint of disease activity before and after antibiotic combination treatment, T-RFLP patterns were also different between the active and inactive phases in the identical patients. Inactive UC patients possessed more diverse microbial compositions. No specific terminal restriction fragments were observed in UC patients. T-RFLP analysis showed that the mucosa-associated microbiota of patients with active UC differed from that of non-IBD controls. Active UC patients possessed significantly fewer diverse microbial compositions.
18,825,588
Comparison of the quick drinking screen and the alcohol timeline followback with outpatient alcohol abusers.
A recent study comparing the Quick Drinking Screen (QDS) with the Timeline Followback (TLFB) found that in a nonclinical population of problem drinkers both measures produced reliable summary measures of drinking. The current study was designed to replicate these findings with a clinical population of alcohol abusers. The data were collected over three years (2004-2006). Participants were 124 alcohol abusers who voluntarily enrolled for outpatient treatment. Over half (52.4%) were female with an average age of almost 40 years. About a third were married, had completed university, and a quarter were unemployed and nonwhite. Participants reported having a drinking problem for an average of 8.3 years, and reported drinking on about 5 days per week, averaging six drinks per drinking day. On two different occasions, they responded to two different sets of questions about their alcohol use. The instruments were: (a) the Quick Drinking Screen (QDS), a summary drinking measure, administered by telephone prior to the assessment; and (2) the TLFB self-administered by computer at the assessment. As in a previous study, this study found that the QDS and the TLFB, two very different drinking measures, collected similar aggregate drinking data for four drinking variables in a clinical sample of alcohol abusers. When it is not necessary or not possible to gather detailed drinking data, the QDS produces reliable brief summary measures of drinking for problem drinkers. Generalization to nonclinical samples awaits further research.
18,825,590
Modulation of insulin concentrations and metabolic parameters in obese patients by -55CT polymorphism of the UCP3 gene secondary to two hypocaloric diets.
Decreased expression or function of UCP3 could reduce energy expenditure and increase the storage of energy. The aim of our study was to investigate the influence of -55CT polymorphism of the UCP3 gene on insulin concentrations and metabolic parameters secondary to two hypocaloric diets in obese patients. A population of 131 obese (body mass index >30), nondiabetic outpatients was analyzed in a prospective way. Before and after 2 months on two different hypocaloric diets, bipolar electrical bioimpedance, blood pressure measurement, serial assessment of nutritional intake with 3 d of written food records, and biochemical analysis were performed. The statistical analysis was performed based on a dominant model. With diet type I (low fat) and diet type II (low carbohydrate) in probands with both wild-type alleles, we observed decreases in BMI, weight, fat mass, systolic blood pressure, leptin levels, and insulin concentrations. In addition, with diet type II, a decrease in diastolic blood pressure, total cholesterol, and triglyceride levels was detected. Secondary to diet type I, a decrease in waist circumference and TNF-alpha was observed. Carriers of the T variant experienced decreases in BMI, weight, and fat mass on both diets, without statistical changes in biochemical parameters. In probands with both C alleles, both diets decreased insulin concentrations, blood pressure, and leptin concentrations. Weight reduction was similar with C and T alleles, independent of macronutrient distribution.
18,825,612
Effect of thymoquinone on ethylene glycol-induced kidney calculi in rats.
The aim of this study was to investigate the effects of thymoquinone, a major component of Nigella Sativa seeds on ethylene glycol-induced kidney calculi in rats. Sixty male Wistar rats were randomly divided into 6 groups (intact control, ethylene glycol control, and 4 experimental groups) and treated for 28 days according to the protocol of the study. The rats in experimental groups received ethylene glycol and intraperitoneal injection of thymoquinone either from the first day of the study or the 15th day, with either doses of 5 mg/kg or 10 mg/kg. Blood and 24-hour urine samples were collected at baseline and on day 28. Urine oxalate and citrate and serum electrolytes were also measured. On day 29, all rats were decapitated and their kidney specimens were studied. On day 28, urine oxalate concentration significantly decreased in the experimental groups compared to the ethylene glycol group (P < .001). Also, serum calcium levels were significantly higher in the experimental groups (P = .001). Calcium oxalate deposits were smaller in the experimental groups than the ethylene glycol group. The mean number of deposits was lower in these groups, too (P < .001). Treatment with the lower dose of thymoquinone was associated with fewer deposits. Thymoquinone significantly decreased the number and size of calcium oxalate deposits in the renal tubules. The dose and duration of treatment, however, does not have a linear relation with the outcomes. Further studies on thymoquinone as a preventive and therapeutic drug for kidney calculi are suggested.
18,825,620
Influence of hypernatremia and polyuria of brain-dead donors before organ procurement on kidney allograft function.
Polyuria and hypernatremia are common problems during the pretransplant care of brain-dead donors. They have not only important role in hemodynamic stability, but also may influence organ transplantation outcomes. The influence of donor hypernatremia in liver transplantation was reported. This study aimed to determine these effects on kidney allograft. We retrospectively studied on 57 transplanted kidney allografts from cadaveric donors. The effects of the urine output volume and serum level of sodium of the donors were on the recipients' serum creatinine levels 1 week after transplantation and at the last follow-up visit were assessed. Of the donors, 58% had polyuria and 45% had hypernatremia. The median pretransplant urine output of the donors was 130 mL/h (range, 35 mL/h to 450 mL/h), and their mean serum sodium level was 152.0 +/- 13.0 mEq/L. Serum creatinine concentrations in the recipients at the 1st posttransplant week correlated significantly with the recipients' age (r = 0.355, P = .02) and the donors' urine output volume (r = 0.329, P = .04). The serum creatinine measured in the last follow-up visit significantly correlated only with the donors' serum sodium levels (r = 0.316, P = .02) and the donors' age (r = 0.306, P = .02). Multivariate regression analysis showed that the donors' serum levels of sodium and potassium were the predictors of the last measured serum creatinine level. Polyuria and hypernatremia in brain-dead donors are frequent. Elevated serum level of sodium and polyuria in the donor can have adverse effects on kidney allograft function.
18,825,624
Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk.
Hereditary diffuse gastric cancer (HDGC) is caused by germline E-cadherin (CDH1) mutations in 25-40% of tested families. Management options for asymptomatic mutation carriers are fraught, since endoscopic surveillance can miss cancer foci and prophylactic gastrectomy has profound clinical sequelae. The aims of this study were to evaluate the impact of current surveillance practices on pre-operative diagnosis and to characterize the microscopic lesions in gastrectomy specimens to better inform clinical practice. Histological assessment and mapping of endoscopic surveillance and gastrectomy specimens were performed for eight asymptomatic CDH1 mutation carriers. E-cadherin expression and proliferation were analysed and evidence of epithelial-mesenchymal transition (EMT) was sought by immunohistochemistry for vimentin and cytokeratin 8/18. Four of eight patients had lesions detected at endoscopic surveillance. A median of 20.5 (range 0-66) signet ring foci were identified per gastrectomy (including in situ lesions and pagetoid spread). Foci were predominantly identified in the fundus and body (90% endoscopic biopsies and 85% in gastrectomy). The likelihood of detecting foci pre-operatively was positively correlated with the number of biopsies taken and the number of lesions in the gastrectomy specimen. E-cadherin expression in gastrectomy specimens was reduced or absent in all of the foci compared with the intervening gastric tissue, suggesting that these lesions are polyclonal. The foci had a low proliferative index (<2%) and there was no evidence for EMT. Multiple endoscopic biopsy sampling of the gastric mucosa increases the yield of microscopic cancer foci. The low proliferative index and lack of EMT suggests that these foci may represent an indolent stage of HDGC.
18,825,658
Developmental impact of a familial GABAA receptor epilepsy mutation.
A major goal of epilepsy research is to understand the molecular and functional basis of seizure genesis. A human GABA(A) gamma2 gene mutation (R43Q) is associated with generalized epilepsy. Introduction of this mutation into a mouse by gene targeting recapitulates the human phenotype demonstrating a strong genotype to phenotype link. GABA(A) receptors play a role in the moment-to-moment control of brain function and also on the long-term wiring of the brain by directing neuronal development. Our objective was to determine whether developmental expression of the mutation alters seizure susceptibility later in life. A tetracycline-based conditional model for activation of a hypomorphic Q43 disease allele was created and validated. Seizure susceptibility was assessed using the subcutaneous pentylenetetrazole model. Seizure susceptibility was significantly reduced in mice where the Q43 allele was suppressed during development. These results demonstrate that a human epilepsy-causing mutation impacts network stability during a critical developmental period. These data suggest that identification of presymptomatic children may provide a window for therapeutic intervention before overt symptoms are observed, potentially altering the course of epileptogenesis.
18,825,662
Enhanced circadian phase resetting in R192Q Cav2.1 calcium channel migraine mice.
Mammalian circadian rhythms are driven by the circadian pacemaker of the suprachiasmatic nucleus (SCN) and are synchronized to the external 24-hour light/dark cycle. After advance time zone transitions (eastbound jet lag), overt circadian rhythms require several days to adjust. The retarded adaptation may protect against acute imbalance of different brain systems. Abrupt circadian rhythm changes may trigger migraine attacks, possibly because migraineurs have an inadequate adaptation mechanism. The novel R192Q knock-in migraine mouse model carries mutated Ca(v)2.1 calcium channels, causing increased presynaptic calcium influx and neurotransmitter release. We investigated whether these mice have an abnormal adjustment to phase advance shifts. We examined phase resetting to 6-hour advance shifts of the light/dark cycle with behavioral and electroencephalographic recordings in R192Q and wild-type mice. We recorded excitatory postsynaptic currents in the SCN, and electrical impulse frequency in vitro and in vivo. R192Q mice showed a more than twofold enhanced adjustment of behavioral wheel-running activity and electroencephalographic patterns, as well as enhanced shifts of electrical activity of SCN neurons in vivo. No differences were found for in vitro recordings of the electrical impulse frequency in SCN slices. R192Q migraine mice lack the physiological retardation in circadian adaptation to phase advance shifts. The opposite findings in vivo and in vitro exclude involvement of the retinal input pathway or the phase-shifting capacity of the SCN. Thus, the physiological inhibitory process appears to be mediated by Ca(v)2.1 channel-dependent afferent signaling from extra-SCN brain areas to the SCN.
18,825,664
Application of intensive care medicine principles in the management of the acute liver failure patient.
1. Acute liver failure is a paradigm for multiple system organ failure that develops as a consequence of sepsis. 2. In the United States, systemic inflammatory response, sepsis, and septic shock are common reasons for intensive care unit admission. Intensive care management of these patients serves as a template for the management of patients with acute liver failure. 3. Acute liver failure is attended by high mortality. Although intensive care results in improved survival, the key treatment is liver transplantation. Intensive care unit intervention may open a "window of opportunity" and enable successful liver transplantation in patients who are too ill at presentation. 4. Intracranial hypertension complicates the course for many patients with acute liver failure. Initially, intracranial hypertension results from hyperemia, which is cerebral edema that reduces cerebral blood flow and eventuates in herniation. The precepts of neurocritical care-monitoring cerebral perfusion pressure, cerebral blood flow, and cortical activity-with rapid response to hemodynamic abnormalities, maintenance of normoxia, euglycemia, control of seizures, therapeutic hypothermia, osmotic therapy, and judicious hyperventilation are key to reducing mortality attributable to neurologic failure.
18,825,685
Comparative expression of Hedgehog ligands at different stages of prostate carcinoma progression.
Recent studies have revealed the potential involvement of Hedgehog (Hh) signalling in proliferation and invasive behaviour of prostate carcinoma (PCa). The aim of this study was to specify the role of Sonic Hh (Shh), Desert Hh (Dhh) and Indian Hh (Ihh) in the natural history of PCa. Hh ligands expression was compared in primary hormone-naive PCa (HNPC), hormone-treated PCa (HTPC) and hormone-refractory PCa (HRPC), using immunohistochemistry. Shh and Dhh were expressed by both epithelial and stromal cells of prostate tissues. Ihh was only expressed by stromal cells. For the three ligands, mRNA and immunostaining were not correlated. In HNPC, Shh epithelial expression was significantly associated with high Gleason scores (p = 0.03), metastatic lymph nodes (p = 0.004) and Dhh epithelial staining was associated with high pT stages (p = 0.003), seminal vesicle invasion (p = 0.03) and bladder neck invasion (p = 0.0008). Negative Shh staining in stromal cells was associated with high Gleason scores (p = 0.015), high pT stages (p = 0.01) and bladder neck invasion (p = 0.04). Concomitant absence of Shh and Dhh expression in stromal cells was an independent prognostic parameter for biological recurrence on multivariate analysis (p = 0.01). Epithelial expression of Shh and Dhh was increased in HTPC compared to HNPC (p = 0.02 and p = 0.04). Interestingly, in vitro, transcript analysis also showed increased expression of these 2 Hh ligands when androgen-sensitive LNCaP cells were maintained in androgen-free medium mimicking hormonal therapy. Epithelial expression of Dhh was increased (p < 0.0001) in HRPC compared to HNPC, while stromal expression of Shh and Dhh was decreased (p < 0.0001). In conclusion, the Hh signalling pathway is associated with pejorative pathological parameters in HNPC and is up-regulated in epithelial cells of HTPC and HRPC. Moreover, the lack of Hh molecules in stromal cells seems to be associated with invasive and hormone-refractory behaviours and suggests specific changes in stromal-epithelial crosstalks during PCa progression.
18,825,689
Energetic analyses of chair and boat conformations of maleimide substituted cyclohexane derivatives.
An analysis of the conformational preferences of two maleimide substituted cyclohexane derivatives proposed as scaffolds for HIV-1 fusion inhibitors is presented. Hybrid Low Mode-Monte Carlo (1:1) conformational searches using seven different force fields were performed in combination with the GBSA(water) solvent model. Low energy structures identified in this way were subjected to geometry optimization on the B3LYP/6-31G** surface. Solvent effects were included in the quantum calculation using the self-consistent reaction field model for water. Quantum results indicate that the 1,3,5-maleimide functionalized 1,3,5-methyl cyclohexane is more stable in the boat conformation, whereas 1,3,5-maleimide functionalized cyclohexane adopts the expected chair conformation with equatorial arms. None of the force fields studied was able to predict the unexpected preference for the boat conformation of 1,3,5-maleimide functionalized 1,3,5-methyl cyclohexane. Comparison of low energy and experimental structures was also performed.
18,825,691
Human parechovirus causes encephalitis with white matter injury in neonates.
To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs. Clinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported. Nine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow-up of one infant was only 9 months. HPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion-weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real-time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures.
18,825,694
Hepatitis C therapy before and after liver transplantation.
1. Pretransplant therapy, using a low-accelerating-dose regimen, is an option for patients with mildly decompensated liver disease and low laboratory Model for End-Stage Liver Disease scores. Achievement of an on-treatment virologic response is the goal of therapy. Preliminary data suggest that up to two-thirds of patients who become hepatitis C virus RNA-negative on treatment will be hepatitis C virus infection-free post-transplantation. 2. Effective prophylactic therapies are not available. Hepatitis C antibody therapy has been ineffective in preventing hepatitis C virus infection in studies to date. 3. Preemptive antiviral therapy started within weeks of transplantation is limited by tolerability, particularly in patients with high Model for End-Stage Liver Disease scores pre-transplantation. Rates of sustained virologic response vary from 8% to 39%. Histological benefits in virologic nonresponders have been demonstrated. 4. Posttransplant antiviral therapy in those with evidence of recurrent disease is the mainstay of management. A combination of pegylated interferon and ribavirin is the treatment of choice, and sustained virologic response is achieved with 48 weeks of treatment in approximately 30% of treated patients. Attainment of early loss of hepatitis C virus RNA is highly predictive of sustained virologic response. Histologic improvements are seen in responders. Survival is prolonged among those achieving a sustained virologic response. 5. Posttransplant antiviral therapy is limited by poor tolerability and the frequent need for dose reductions and/or discontinuation. Immunologic complications, including acute rejection, chronic rejection, and autoimmune-like hepatitis, occur in association with therapy, albeit at low rates. 6. Hepatitis C virus-infected liver transplant recipients represent an important patient population in need of new therapeutics options to prevent patient and graft losses due to recurrent hepatitis C virus disease.
18,825,697
High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation.
High mobility group box 1 protein (HMGB1), a cytokine actively secreted by phagocytes and passively released from necrotic cells, is an inflammatory mediator in experimental hepatic ischemia/reperfusion injury. We characterized its expression in human liver transplantation. In 20 patients, in addition to systemic samples, blood was drawn from portal and hepatic veins during and after reperfusion to assess changes within the graft. Plasma HMGB1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured, and HMGB1 immunohistochemistry was performed on biopsies taken before and after reperfusion. Plasma HMGB1 was undetectable before reperfusion, and levels in systemic circulation peaked after graft reperfusion. At portal declamping, HMGB1 levels were substantially higher in the caval effluent [188 (80-371) ng/mL] than in portal venous blood [0 (0-3) ng/mL, P < 0.001]. HMGB1 release from the graft continued thereafter. HMGB1 levels were not related to TNF-alpha or IL-6 levels. HMGB1 expression was up-regulated in biopsies taken after reperfusion (P = 0.020), with intense hepatocyte and weak neutrophil staining. HMGB1 levels in hepatic venous blood correlated with graft steatosis (r = 0.497, P = 0.03) and peak postoperative alanine aminotransferase levels (r = 0.588, P = 0.008). Our results indicate that HMGB1 originates from the graft and is a marker of hepatocellular injury in human liver transplantation.
18,825,712
Management of patients with decompensated hepatitis B virus associated [corrected] cirrhosis.
1. Hepatitis B virus replication is associated with a severe outcome in patients with decompensated cirrhosis. 2. Viral suppression induced by antivirals results in a clinical improvement that allows liver transplantation to be delayed or avoided. 3. Early treatment intervention is mandatory in patients with decompensated cirrhosis because of the delay in the restoration of liver functions. 4. Lamivudine is no longer the drug of choice because the initial enthusiasm has been tempered by the high rate of resistance development. 5. Early add-on therapy with adefovir allows us to rescue lamivudine resistance, but its use may be limited by nephrotoxicity. 6. Studies are ongoing with the newer generation of antivirals (telbivudine, tenofovir, entecavir, and emtricitabine) in monotherapy or in combination to determine the best strategy for achieving rapid and prolonged suppression of viral replication. These improved strategies should enhance treatment success enough to obtain clinical stabilization, to delay or prevent the need for transplantation, and to reduce the risk of hepatitis B virus recurrence on the graft.AASLD.
18,825,719
Liver transplantation for hepatitis B: what is the best hepatitis B immune globulin/antiviral regimen?
1. Prophylaxis using the combination of lamivudine and high-dose intravenous hepatitis B immunoglobulin (approximately 10,000 IU monthly) reduces the long-term risk of recurrence of hepatitis B in hepatitis B surface antigen-positive transplant recipients to 5% to 10%. However, this therapy is expensive and inconvenient for patients. 2. Recent studies have shown that similar results can be obtained, at far less cost, with much lower doses of intramuscular hepatitis B immune globulin (400-800 IU monthly) in combination with pretransplant and posttransplant lamivudine therapy. 3. The development of lamivudine resistance pre-transplant can lead to hepatic decompensation and increases the risk of posttransplant recurrence in patients receiving hepatitis B immune globulin/lamivudine prophylaxis. Newer nucleos(t)ide analogues with lower resistance rates such as entecavir, adefovir, and tenofovir should therefore replace lamivudine in hepatitis B prophylaxis. 4. Combination therapy with these newer agents and low-dose intramuscular hepatitis B immune globulin is likely to be the most cost effective hepatitis B immune globulin-containing regimen for the prevention of hepatitis B recurrence post-transplant. 5. Some form of hepatitis B virus prophylaxis needs be continued indefinitely post-transplant. However, the use of antivirals with very low rates of drug resistance will make it possible to stop hepatitis B immune globulin therapy in many patients currently receiving hepatitis B immune globulin/nucleos(t)ide combination therapy.
18,825,721
The relationships among self-esteem, stress, coping, eating behavior, and depressive mood in adolescents.
The prevalence of adolescent overweight is significant, almost 25% in some minorities, and often is associated with depressive symptoms. Psychological and psychosocial factors as well as poor coping skills have been correlated with unhealthy eating and obesity. The purpose of this study was to examine relationships among self-esteem, stress, social support, and coping; and to test a model of their effects on eating behavior and depressive mood in a sample of 102 high school students (87% minority). Results indicate that (a) stress and low self-esteem were related to avoidant coping and depressive mood, and that (b) low self-esteem and avoidant coping were related to unhealthy eating behavior. Results suggest that teaching adolescents skills to reduce stress, build self-esteem, and use more positive approaches to coping may prevent unhealthy eating and subsequent obesity, and lower risk of depressive symptoms.
18,825,731
DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation.
DNA polymerase eta (POLH) is required for the generation of A:T mutations during the somatic hypermutation of Ig genes in germinal center B cells. It remains unclear, however, whether POLH is a limiting factor for A:T mutations and how the absence of POLH might affect antibody affinity maturation. We found that the heterozygous Polh+/- mice exhibited a significant reduction in the frequency of A:T mutations in Ig genes, with each type of base substitutions at a level intermediate between the Polh+/+ and Polh(-/-) mice. These observations suggest that Polh is haplo-insufficient for the induction of A:T mutations in Ig genes. Intriguingly, there was also a reduction of C to T and G to A transitions in Polh+/- mice as compared with WT mice. Polh(-/-) mice produced decreased serum titers of high-affinity antibodies against a T-dependent antigen, which was associated with a significant reduction in the number of plasma cells secreting high-affinity antibodies. Analysis of the V region revealed that aa substitutions caused by A:T mutations were greatly reduced in Polh(-/-) mice. These results demonstrate that POLH is a limiting factor for A:T mutations and contributes to the efficient diversification of Ig genes and affinity maturation of antibodies.
18,825,746
Plasmodium vivax parasites alter the balance of myeloid and plasmacytoid dendritic cells and the induction of regulatory T cells.
Immunity induced by Plasmodium vivax infections leads to memory T-cell recruitment and activation during subsequent infections. Here, we investigated the role of regulatory T cells (Treg) in coordination with the host immune response during P. vivax infection. Our results showed a significant increase in the percentage of FOXP3+ Treg, IL-10-secreting Type I Treg (Tr1) and IL-10 levels in patients with acute P. vivax infection as compared with those found in either naïve or immune controls. The concurrent increase in the Treg population could also be reproduced in vitro using peripheral blood mononuclear cells from naïve controls stimulated with crude antigens extracted from P. vivax-infected red blood cells. Acute P. vivax infections were associated with a significant decrease in the numbers of DC, indicating a general immunosuppression during P. vivax infections. However, unlike P. falciparum infections, we found that the ratio of myeloid DC (MDC) to plasmacytoid DC (PDC) was significantly lower in acute P. vivax patients than that of naïve and immune controls. Moreover, the reduction in PDC may be partly responsible for the poor antibody responses during P. vivax infections. Taken together, these results suggest that P. vivax parasites interact with DC, which alters the MDC/PDC ratio that potentially leads to Treg activation and IL-10 release.
18,825,754
Microimaging FTIR of head and neck tumors. IV.
On continuing our studies on head and neck neoplasia, specimens from salivary gland tumors have been explored by using infrared microimaging spectroscopy to discern healthy from neoplastic tissues. Samples with Warthin tumor, epithelial displasia, marginal B-cell lymphoma, low-grade adenocarcinoma, and adenoid cystic carcinoma pathologies have been investigated by using conventional light sources. Changes were monitored at the molecular level, probing spectral markers such as Amide I and II, phosphate, nucleic acids, and carbohydrates vibrational modes. In all cases, supervised and unsupervised spectral analyses resulted in satisfactory agreement with histopathological findings.
18,825,780
[Fifth revolution in medicine: on the role of infections in pathogenesis of aging and chronic diseases].
The XXth century is marked by the substantial increase in human life expectancy. Historically, main reasons for that are four achievements of medicine: (1) improvements in common hygiene, such as waste disposal and water purification which led to the significant reduction of communicable diseases; (2) common recognition of Pasteur's Germ Theory followed by improvements in occupational and personal hygiene as well as introduction of antiseptic and aseptic measures; (3) decrease in childhood mortality due to the discovery and widespread application of vaccination; and (4) the discovery and clinical application of antibiotics. An epidemiological transition took place, i.e. the shift from communicable infectious diseases, as a main cause of morbidity and mortality, to chronic degenerative diseases, mainly considered non-infectious. Experimental evidence has been accumulated on a significant number of microorganisms, including viruses (such as a group of herpes viruses, hepatitis viruses, etc.), bacteria (Chlamydia, Helicobacter, periodontal pathogens, etc.), fungi and parasites, as an underlying reason for many of diseases, such as atherosclerosis, various cancers, type 1 and 2 diabetes, neurodegenerative and some psychiatric diseases, osteoporosis, autoimmune diseases and others. On the other hand, most of these diseases have been traditionally associated with age, together with other "age-related" disorders, such as immune system suppression, thymus involution, pathologic calcification, etc. Taken together, these facts suggest that aging, among others, has infectious origins, and that burden of infections may lead to enhanced senescence and premature death. In fact, infections may serve as a trigger of senescence, presumably via the mechanisms of chronic oxidative stress, low-grade inflammation, telomere shortening, and autoimmune processes due to the molecular mimicry. We believe that next step in human longevity increase can be possible by common appreciation of the role of infections as the main trigger of age-related diseases and disorders, and by efforts to cure and/or eradicate these infections.
18,825,837
Intersex mental health and social support options in pediatric endocrinology training programs.
The birth of a child with an intersex condition is often an emotionally stressful event for parents. Preparation and ongoing support systems could be beneficial to both parents and children and would alleviate some of the shame and isolation associated with intersex conditions. To assess the extent to which psychological support is available, a short e-mail survey on this topic was sent to the directors of 50 pediatric endocrinology fellowship training programs (PEFTPs), who are most likely to evaluate and treat intersex children and their parents. Of the 29 PEFTPs that responded, 69% offer psychological support and 58% have a mental health specialist on staff. However, only 19% of patients or families receive emotional support during diagnosis and only 15% receive support after diagnosis. We found two barriers that prevent patients and families from receiving psychological help from their intersex care team. First, there is a lack of training for mental health professionals regarding the needs of intersex patients and families. Second, some families refuse help even though it is offered. This study reveals that further research is needed to overcome these two barriers regarding mental health treatment of intersex patients and families.
18,825,861
Professional regulation in nursing. Part 2: Political change.
The current Government came to power in 1997. In their manifesto, changes in ideology towards the provision of health and the place of those who provided health care were evident. As well as the issue of acceptable standards of healthcare provision, the issue of the regulation of nurses and other health workers was perused. This article reviews the political manifestos of 1997 and 2001, and reflects on the changes averred to in the context of the effects to the nursing profession in respect of professional regulation and central control by the Government of the profession as a whole. A conclusion is reached that political changes, not based on theoretical models of care, but rather on reports commissioned by Government, have resulted in far reaching consequences for nursing. This includes the replacement of the regulatory body (United Kingdom Central Council for Nursing, Midwifery and Health Visiting) with a new body (Nursing and Midwifery Council) and the inclusion of public persons into the management of nurses to the extent that for the first time, lay persons would have an influence in the outcomes of professional disciplinary hearings and sanctions.
18,825,855
Study of glucose profiles with continuous glucose monitoring in adolescents with poorly controlled type 2 diabetes mellitus.
To evaluate glycemic excursions in adolescents with poorly controlled type 2 diabetes mellitus (DM2). Seventeen adolescents (12 F/5 M) underwent glucose monitoring for 3 days using a continuous glucose monitoring system (CGMS). Glucose measurements were divided into periods of euglycemia, hyperglycemia, and hypoglycemia. The percentage of each period, average glucose concentration per 24 h, day and night, the number of excursions, and area under the curve (AUC) of glucose >150 mg/dl and <70 mg/dl were calculated. On average, patients remained in euglycemia for 28.5%, hyperglycemia for 70%, and hypoglycemia 1.3% of the total day. Hyperglycemic excursions were more frequent during the day. Hypoglycemic events were more frequent during the night. 24-h average glucose, duration of glucose >150 mg/dl, and AUC >150 mg/dl correlate with HbA1c and fructosamine to varying degrees. Continuous glucose monitoring provide valuable information on glucose excursions in adolescents with poorly controlled DM2 and may be helpful in improving metabolic control of poorly controlled adolescents with DM2.
18,825,872
[Value of basic and intensive management of patients with heart failure; results of a randomised controlled clinical trial].
To determine the efficacy of 2 nurse-directed programmes of different intensity for the counselling and follow-up of patients hospitalised for heart failure, compared with standard care by a cardiologist. Multicentre randomised clinical trial (www.trialregister.nl: NCT 98675639). A total of 1023 patients were randomized after hospitalisation for heart failure to 1 of 3 treatment strategies: standard care provided by a cardiologist, follow-up care from a cardiologist with basic counselling and support by a nurse specialising in heart failure, or follow-up care from a cardiologist with intensive counselling and support by a nurse specialising in heart failure. Primary end points were the time to rehospitalisation due to heart failure or death and the number of days lost to rehospitalisation or death during the 18-month study period. Data were analysed on an intent-to-treat basis. Mean patient age was 71 years, 38% were women, 50% had mild heart failure and 50% had severe heart failure. During the study, 411 patients (40%) were rehospitalised due to heart failure or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (differences not significant). The time to rehospitalisation or death was similar in the 3 groups: hazard ratios for the basic and intensive support groups versus the control group were 0.96 (95% CI: 0.76-1.21; p = 0.73) and 0.93 (95% CI: 0.73-1.17; p = 0.53), respectively. The number of days lost to rehospitalisation or death was 39,960 in the control group; this number was 15% less in the intervention groups, but the difference was not significant. However, there was a trend toward lower mortality in the intervention groups. In all 3 groups, more visits occurred than planned, which may have had a considerable effect on care, notably in the control group. The results of this study indicated that the provision of additional counselling and support by a nurse specialising in heart failure as an adjuvant to intensive follow-up care provided by a cardiologist does not always lead to a reduction in rehospitalisation frequency.
18,825,890
Screening for retinopathy of prematurity in a tertiary care newborn unit in Turkey: frequency, outcomes, and risk factor analysis.
To report the frequency, risk factors, and outcomes of screening for retinopathy of prematurity (ROP). Data of neonates with a gestational age of 34 weeks or less were analyzed and the predictors on the development of ROP were determined by using logistic regression analysis. Of the 318 neonates, the frequency of ROP was 37.1% for any stage and 7.2% for stage 3 or greater. Treatment was needed in 16.1% of neonates with ROP. No treatment was required in neonates with a gestational age of greater than 32 weeks. Oxygen therapy, sepsis, gestational age of 32 weeks or less, and birth weight of less than 1,250 g were determined as the independent risk factors. Although frequency of ROP in Turkey is similar to that in the United States, the rate of severe ROP necessitating treatment seems to be higher in Turkey. Neonates with a gestational age of 32 weeks or less, a birth weight of less than 1,250 g, sepsis, and oxygen therapy may have a greater risk of developing ROP and screening should be intensified in the presence of these risk factors.
18,825,902
Periorbital cellulitis in the era of Haemophilus influenzae type B vaccine: predisposing factors and etiologic agents in hospitalized children.
The incidence of Haemophilus influenzae type B (HIB) infection, once the most common cause of periorbital cellulitis, declined dramatically after the introduction of HIB vaccine in 1990. The aim of the current study was to determine the predisposing factors and agents in the pathogenesis of periorbital cellulitis in hospitalized children in the post-HIB vaccination era. Children with clinical findings of periorbital inflammation who were hospitalized in a tertiary pediatric hospital in Israel in 2000-2001 were observed prospectively. Special attention was directed to the predisposing medical condition in each case. One hundred sixty-three patients had a final discharge diagnosis of periorbital cellulitis. Mean age was 34 months (median = 24 months). The predisposing conditions were conjunctivitis (42.9%), infected wound or trauma (20.9%), insect bites (9.8%), sinusitis (8%), dacryostenosis (4.9%), and Streptococcus pneumoniae bacteremia (0.6%). Children with conjunctivitis and sinusitis had the most severe inflammatory signs. None of the cultures was positive for HIB, although only 71% of the children had complete immunization. The epidemiology of periorbital cellulitis in children has changed in the post-HIB vaccine era. The most common predisposing medical conditions are conjunctivitis or an infected wound in the vicinity of the eye. Bacteremia is rarely a source of the disease. These findings have important clinical implications in terms of choice of treatment.
18,825,903
Agmatine inhibits hypoxia-induced TNF-alpha release from cultured retinal ganglion cells.
The effect of hypoxia on the release of tumor necrosis factor-alpha (TNF-alpha) in transformed rat retinal ganglion cells (RGCs) and the effect of agmatine on the hypoxia-induced production of TNF-alpha in RGCs were evaluated. RGCs were cultured under hypoxic conditions with 5% oxygen, with or without 100 microM agmatine. The expression levels of TNF-alpha and its receptor-1 (TNF-R1) were investigated by Western blot analysis. After 6 hours of hypoxia, we noted an increase in TNF-alpha production in RGCs. Agmatine significantly reduced TNF-alpha level after 12 hours of hypoxic treatment. The expression of TNF-R1 was not affected by the hypoxia or agmatine treatment. Our results show that agmatine inhibits the TNF-alpha production of RGCs in hypoxic condition. These results demonstrate a possible neuroprotective mechanism for agmatine against hypoxic damage in RGCs.
18,825,914
[Characteristic features of the ranks genus and subgenus, and an intercalary rank "species complex" in ixodid ticks (Acari: Ixodidae)].
The work was carries our from the standpoint of the morphological conception of species. Vast collections of the Zoological Institute of the Russian Academy of Science testify to the existence of hiatuses in both genera and subgenera of Palearctic ixodids at all active phases of their ontogenesis. The fact that the subgenera of Palearctic genera have been well studies is notes, and composition of the subgenera is presented. The question of a taxonomic intercalary rank "species complex" is considered in detail in the context of the coevolution between some complexes of closely related species of ixodid ticks and some closely related species (genospecies, strains) of pathogens. The question of the taxonomic rank "species complex" in ixodid ticks as a phyletic species association is postulated on the basis of comparative ontogenetic data. Nomenclature status of the intercalary association "species complex" is specified in conformity with the fourth edition of the International Code of Zoological Nomenclature. Species composition of most studied complexes is presented. Some variants of morphological differentiation between species complexes within subgenus are considered. Significance of the taxonomic concept "species complex" for zoological. parasitological, and medical aspects of the ixodid ticks study was evaluated. Prognostic significance of the rank "species complex" for the study of the relationships between ixodid ticks and pathogens is discussed.
18,825,916
[Component parasite communities in the minnow Phoxinus phoxinus (L.) from ecologically safe and polluted reservoirs].
A comparative analysis of the structure of component parasite communities in the minnow from ecologically safe or polluted to variable extent reservoirs was made. The analysis showed that the increase of the reservoir pollution by everyday drains, washings of fertilizers from the fields around and the dacha sections causes the change of dominant parasite species in the minnow, alteration of the sum of errors in the regression equation characterizing the spread of values of biomasses of the species forming the parasite community, and change of the "graphic" structure of the community. It is proved, that the high concentration of biogens has a destructive effect on natural systems, and at the same time causes the process of self-organizing, leading to the alteration of the community structure. As soon as even a small part of biogens is stopped to come into the reservoir, and the quality of environment is restored, the community restores its structure.
18,825,919
[Chitinases in bioengeneering research].
Techniques of introduction of foreign genes into the plant genome have been intensely developed in order to directionally improve properties of crops. One of the key directions in plant bioengineering is searching for and analyzing promising genes, in particular, to construct genotypes with high resistance to pathogens and pests. In this review, the use for this purpose of transgenes coding for chitinase family enzymes is considered. Many of these transgenes have proved to be efficient factors for elevating plant resistance to pathogenic fungi.
18,825,950
[Phylogeography of the Siberian newt (Salamandrella keyserlingii) by mitochondrial DNA sequence analysis].
Differentiation of geographical populations of the Siberian newt Salamandrella keyserlingii throughout the species range was analyzed using a fragment of the cytochrome b gene. The population of the Primorye region (Russian Far East) is separated to the greatest extent; the Japanese and South Kuril populations are the next most separate. These populations are possibly subspecies. Geographical differentiation of populations in the Siberian part of the species range is lower, lacks a clinal variation, and is irregular. The molecular variation of S. keyserlingii supports the hypothesis that several primary vicarious refugia of pre-Pleistocene differentiation of a common ancestor of Salamandrella occurred in the southeastern part of its current distribution range and that northern and western regions were gradually colonized via repeated steps of expansion and retreat in the Siberian part of the modem species range.
18,825,958
[Instability of B-chromosomes in somatic and germline cells of Apodemus peninsulae].
Instability of B-chromosomes was estimated in somatic and germline cells of samples Apodemus peninsulae from different localities of the species range. In 84 out of 188 animals (45%), in cells assessed for B-chromosome mosaicism, bone marrow cells with different B-chromosome number were observed. The numbers of B-chromosomes in spermatocytes at the pachytene stage were estimated in ten males. It was shown that the average number of B-chromosomes and the number of cell clones in germline cells was higher than the corresponding numbers in bone marrow cells. The higher number of B-chromosomes and their higher variability in germline cells than in somatic cells suggest the existence of a mechanism of premeiotic accumulation of B-chromosomes in spermatogenesis of A. peninsulae.
18,825,959
[Effect of vitamin concentration on the synthesis of lactate, ethanol, pyruvate, and ethyl acetate in cells of the yeast Dipodascus magnusii].
In the yeast Dipodascus magnusii, which is auxotrophic for thiamine and biotin, during cultivation on glucose with excessive thiamine concentration, pyruvate metabolism was shown to result in the synthesis of fermentation products, namely, ethanol and, to a lesser extent, lactate. Substantial synthesis of ethyl acetate was also observed under these conditions. Introduction of nicotinic acid (NA) into the medium resulted in time separation of ethanol and lactate production. It was shown that cultivation of the yeast under biotin deficiency resulted in nearly complete suppression of aerobic production of ethanol and cessation of ethyl acetate synthesis, whereas lactate synthesis was activated as early as in the first hours of cultivation. Upon introduction of NA under these conditions, lactate concentration sharply increased. These results show that the combination of thiamine and biotin with other vitamins can stimulate utilization of the pyruvate pool in yeasts towards formation of considerable amounts of lactate, which is typical only of cells of higher eukaryotes and bacteria.
18,825,974
[Growth and biosynthesis of rugulovasines in Penicillium variabile Sopp 1912].
Production of clavine alkaloids rugulovasines by P. variabile did not depend on the habitat of the producers. During submerged cultivation on a simple synthetic medium in early growth stages, microcyclic conidiation was observed in the tested fungi; its presence or absence, as well as the activity of the cultures as to biosynthesis of rugulovasines, depended on the composition of the culture medium. On a complex medium supplemented with peptone, conidiation occurred but was considerably suppressed. Conidia were completely absent in the medium supplemented with yeast extract. In both cases, no appreciable amounts of rugulovasines were detected.
18,825,977
[The structure of micromycete complexes in permafrost and cryopegs of the Arctic].
A comparative study of the structure of micromycete complexes has been performed. The samples of micromycetes were taken by boring from unique habitats: cryopegs (lenses of non-freezing hypersaline water in ancient permafrost horizons) and permafrost Arctic sediments of different age enclosing these cryopegs. The possibility of characterizing the above habitats by the structure of specific complexes of microscopic fungi using qualitative and quantitative indices at extremely low numbers of these organisms was demonstrated.
18,825,982
[The alteration of attractiveness of intact males mice to females chemosignals, subjected of ionizing radiation in sublethal dose].
After irradiation in a dose 4 Gy female mice of CBA and C57Bl/6 (female CBA during 18-23 days, female C57Bl/6 - 4-10 days) secretes with urine volatile components (chemosignals) which possess higher, than secretes intact females, attractiveness for intact males the same strains irrespective of a genotype. When estimation relative attractiveness postradiation secretes female mice CBA and C57Bl/6 intact males prefer chemosignals singenic (genetically identical) females during 1-23 day after irradiation. Observed olfactorial reaction male mice more differ from norm. In which males prefer chemosignals of allogenic (with a strange genotype) females. This disturbances identifed as postradiation reversion attractiving males of chemosignals, dependent on the genotype of females. Typical for norm chemosignalisation at females restored for 43 days after the irradiation. The mechanism and biological advisability of this phenomenon are discussed.
18,825,987
Out-of-school participation patterns in children with high-functioning autism spectrum disorders.
This study examined differences in out-of-school activity participation between typically developing children and those with high-functioning autism spectrum disorders (HFASD). Children with HFASD, ages 6 to 12 (N = 52), and a control group (N = 53) were assessed using the Children's Assessment of Participation and Enjoyment and the Social Responsiveness Scale. Significant differences were seen in participation between typical and HFASD groups in number of activities in which children participate, the numbers of individuals with whom they participate, and the variety of environments in which they participate. These findings indicate that out-of-school participation is significantly different for children with HFASD than for typically developing peers. Findings suggest that social impairment is related to some aspects of participation and that addressing social skills in intervention could contribute to increased participation in out-of-school activities by children with HFASD, which would contribute to their long-term mental and physical health.
18,826,016
Feeding patterns of Haemagogus capricornii and Haemagogus leucocelaenus (Diptera: Culicidae) in two Brazilian states (Rio de Janeiro and Goiás).
We present the identification of bloodfeeding sources of Haemagogus (Haemagogus) capricornii Lutz and Haemagogus (Conopostegus) leucocelaenus (Dyar & Shannon) (Diptera: Culicidae) from different regions of Brazil, as analyzed by precipitin tests. Anti-sera for bird, bovine, equine, human, opossum, and rodent were used. Two hundred one mosquitoes were examined (147 Hg. leucocelaenus and 54 Hg. capricornii), of which 177 reacted for some anti-serum. For Hg. leucocelaenus, 86 (68.3%) reacted to one blood source, 38 (30.2%) to two sources, and two (1.6%) to three sources; the combinations of bird + human (18.4%), bird + rodent (15.8%), and bird + marsupial (15.8%) were the most frequent. For Hg. capricornii, 34 (66.7%) reacted to one blood source; combinations bird + rodent (37.5%) and bird + marsupial (25%) were the most frequent combinations. Mosquito preference for bloodfeeding sources was different in these areas, possibly because of the availability of sources. This diversity of sources can have important epidemiological implications.
18,826,029
Novel arthropod repellent, BioUD, is an efficacious alternative to deet.
For >50 yr, N,N-diethyl-3-methylbenzamide (deet) has been the standard for arthropod repellents and has been an important tool to protect people from disease agents carried by ticks, mosquitoes, and other arthropods. However, some people avoid using deet because of concerns about adverse health effects. In 2007, a new repellent, BioUD, with the active ingredient 7.75% 2-undecanone, originally derived from wild tomato (Lycopersicon hirsutum Dunal f. glabratum C. H. Müll) plants, was registered by the U.S. Environmental Protection Agency. In the current study, repellent efficacy of BioUD was compared using arm-in-cage studies with 7 and 15% deet against the mosquitoes Aedes aegypti (L.) and Aedes albopictus Skuse. No differences were found in mean repellency over 6 h after application between BioUD versus 7 and 15% deet for Ae albopictus. For Ae. aegypti, no differences were found over the same time period for 7% deet. Compared with 15% deet, BioUD mean repellency was lower over the 6-h test period. Human subject field trials were conducted in North Carolina, United States, and Ontario, Canada, comparing the repellency of BioUD to products containing 25 and 30% deet. BioUD provided the same repellency or was more efficacious than 25 and 30% deet, respectively, in these studies. Laboratory trials were conducted to determine the repellent activity of BioUD against the American dog tick, Dermacentor variabilis (Say), on human skin and cloth. BioUD repelled ticks at least 2.5 h after application to human skin. On cloth, no differences in mean repellency were found through 8 d after application between BioUD and 7% deet. In a two-choice test for BioUD versus 15% deet on filter paper, ticks spent significantly more time on the deet-treated surface than the BioUD-treated surface. Based on these studies in toto, BioUD is an efficacious alternative to deet in its repellent activity.
18,826,032
Blood-feeding behavior of vesicular stomatitis virus infected Culicoides sonorensis (Diptera: Ceratopogonidae).
To determine whether vesicular stomatitis virus (VSV) infection of Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae) affects subsequent blood-feeding behavior, midges injected with either virus-infected or virus-free cell lysates were allowed to blood feed for short (10-min) or long (60-min) periods on 2, 3, and 4 d postinoculation (DPI). Generalized linear mixed models were fit to test the effects of infection status, duration of feeding period, and DPI on the percentage of females that blood fed. VSV-infection significantly reduced the percentage of females that blood fed on 2 DPI, the day of peak virus titer. On 3 DPI a significantly greater percentage of midges blood fed when allowed 60 min to feed. This effect was not seen on 2 and 4 DPI and was not dependent on VSV infection status. The impact of changes in blood-feeding behavior by infected insects on virus transmission is discussed.
18,826,036
Host feeding pattern of Japanese encephalitis virus vector mosquitoes (Diptera: Culicidae) from Kuttanadu, Kerala, India.
Identification of blood meals of vector mosquitoes is an important tool in the epidemiological investigations of vector-borne diseases. The blood meals of three mosquito species involved in the transmission of Japanese encephalitis virus (JEV) from the Kuttanadu area, Kerala, were determined using the agarose gel diffusion technique. A total of 4959 blood smears belonging to Culex (Culex) tritaeniorhynchus Giles (3273), Cx. (Culex) gelidus Theobald (64), Mansonia (Mnd.) indiana Edwards (735) ,and Ma. (Mnd.) uniformis (Theobald) (887) were tested. Cx. tritaeniorhynchus had predominantly fed on bovids (46.4%), and a good proportion (29%) had fed on more than one host. Cx. tritaeniorhynchus was highly zoophagic, and human feeding accounted for only 1.5% of those individuals successfully tested. Cx. gelidus showed bovid feeding at 36% and pig feeding at 12.5%. The test results showed 42.3% Ma. indiana and 12.2% Ma. uniformis had fed on humans. Multiple feeding was observed in Ma. indiana and Ma. uniformis, and most of the double feedings were from bovids and ovids (7.9 and 20.1%, respectively). Pig feeding accounted for 4.8% of the feedings by Cx. tritaeniorhynchus, 5.3% of Ma. indiana, and 6.4% of Ma. uniformis. This study is significant because of the role played by these mosquitoes in the transmission of JEV in the Kuttanadu area of Kerala, India.
18,826,037
Mosquito vectors of West Nile Fever in Israel.
West Nile fever (WNF) is endemic in Israel. In 1999, country-wide adult mosquito surveys were initiated and intensified after the 2000 country-wide outbreak of WNF in humans. In 8 consecutive yr, groups of male and female specimens of different species and from different locations were tested for infection with West Nile virus (WNV). Three species made up >87% of the total catch: Culex pipiens L. (52%), with an infection rate (IR) of 0.5; Cx. perexiguus Theobald (20%), with an IR of 2.7; and Aedes caspius Pallas (15%), with an IR of 0.6. The geographical and temporal distribution of WNV-infected mosquitoes was similar but was not parallel to the seasonal abundance of the populations. The seasonal occurrence of human cases is in correlation with the finding of WNV-positive mosquito specimens reaching a peak 1 mo later than the mosquito peak. The relative importance of the mosquito species in the epidemiology of WNF is discussed. Cx. perexiguus is considered the major vector of WNF in Israel.
18,826,039
Prevalence of spotted fever group rickettsiae in Ixodes ricinus (Acari: Ixodidae) in southern Germany.
Host-seeking Ixodes ricinus (L.) (Acari: Ixodidae) ticks were collected systematically, from May to September 2006, at selected sites in southern Germany, including a large city park in Munich. Polymerase chain reactions for amplification of genes of the rickettsial citrate synthase (gltA), the outer membrane proteins A and B (ompA and ompB), and the 16S rDNA were used to investigate 2,861 specimens (adults and nymphs). GltA sequences of spotted fever group rickettsiae were detected in 151 of all samples (5.3%; 95% CI = 4.3-6.2%). Sequencing revealed Rickettsia helvetica in 91.4% of the samples and R. monacensis in 8.6%. Amplification of ompA was not possible for R. helvetica, but in all except one of the R. monacensis. The results were analyzed statistically to test the effects of season, location, developmental stage, and gender of the tick on prevalence of Rickettsia spp. Although rickettsial DNA was detected in all investigated sites, sites in natural forest areas had significantly higher prevalences than sites in landscaped city parks. Adult female and male ticks had a similar prevalence and were significantly more often infected than nymphs. Monthly differences were not statistically significant. These results clearly show that R. helvetica is widespread throughout the study region and could result in a threat to public health in areas of high prevalence.
18,826,040
Methods for the purification of HQ-tagged proteins.
The HQ (H = histidine, Q = glutamine) tag is a small fusion tag that can be isolated using immobilized metal affinity columns. HQ-tagged proteins can be expressed and purified from bacterial cells under native and denaturing conditions, mammalian cells, insect cells, wheat germ and rabbit reticulocyte. Furthermore, HQ-tagged proteins can be purified using magnetic or non-magnetic resins in multiple formats from small to large-scale and manual or automated. In this chapter, we have described various protocols for the purification of HQ-tagged proteins.
18,826,054
Amylose affinity chromatography of maltose-binding protein: purification by both native and novel matrix-assisted dialysis refolding methods.
Maltose-binding protein (MBP) is a carrier protein for high level recombinant protein and peptide production from either the cytoplasm or periplasm of Escherichia coli. The affinity matrix for purifying MBP-passenger proteins utilizes amylose covalently attached to magnetic beads, agarose, or a chemically inert fast protein liquid chromatography (FPLC) matrix--exploiting the natural affinity of MBP for alpha-(1-->4)-maltodextrins in the stationary phase. A fundamental problem is the expression and purification failure of as much as 30% of all constructs, which is limiting for one of the best solubilizing carrier proteins available for recombinant expression. In this chapter, we have discussed aspects of MBP biology that can impact upon binding to the amylose affinity matrix including cloning considerations, structural complications, hydrophobic buffer additives and the presence of cellular biomolecules that bind or modify the matrix during purification. Chromatography conditions are presented for purification at very small scales of less than 0.5 mL using amylose magnetic beads, a batch and semi-batch method for small to moderate scale purifications up to approximately 35 mg and larger scale FPLC methods. A novel matrix-assisted dialysis refolding method is also described whereby MBP-passenger proteins can be refolded in the presence of amylose matrix in instances where native purification methods fail to bind the amylose matrix.
18,826,055
[Amputation as a treatment for complications on a traumatic dislocations of the knee. Case report].
Vascular lesion associated with knee dislocation represents a common and potentially devastating complication. A delay in revascularization that exceeds 8 hours can lead to amputation of the extremity. Therefore it is mandatory to do an immediate examination and an effective diagnosis to rule out this complication. A 19-year-old male was struck by a motor vehicle and caused traumatic dislocation of the left knee as observed on X-rays. The knee was reduced immediately. At 12 hours, the patient presented edema on the extremity and was then stabilized with external fixators. On the third day the patient developed a compartmental syndrome and artery obstruction, and required fasciotomies and revascularization of the popliteal artery. Twenty four hours later, again the artery was obstructed, conducing to supracondylar amputation. The purpose of this article is to show that a knee dislocation, with vascular complications, may lead to extremity amputation as a drastic treatment. It is important to emphasize that vigilance of vascular permeability has to be followed every 2-3 hours, for at least 72 hours after the injury, and assisted with Doppler study. And if needed, at the moment when a pulse abnormality is detected an arteriography study must be realized.
18,826,085
[Cochlear implantation in the ossified cochlear].
To explore the problems and describe clinical experiences associated with multichannel cochlear implantation in patients with cochlear ossification. Seven cochlear implant cases with bilateral cochlear ossification from 1996 to 2006 in Beijing Tongren Hospital were retrospectively reviewed, 4 of which were the consequence of meningitis. Three patients' cochlear were completely ossified, 1 patient's tympanic scala was completely ossified, 1 patient's cochlear was partially ossified, and 2 patients' cochlear were partially fibrotic. This article addressed the components of the preoperative evaluation, surgical decision-making, and specific techniques for cochlear implant array insertion in all kinds of ossified cochlea. Gusher was found in 1 case but less serious than that with inner ear malformations. The electrodes were inserted in the cochleostomy in full length in 4 cases, 1 case gave up, and the cochlear implant array were partially inserted in the remains. No serious complications occurred after implantation. All patients had auditory sensations. The impedance of the electrodes, the T level, C level and the hearing threshold were slightly higher than that of the normal cochlear implantation. The key influencing factor of ossified cochlear patients were the degree of the disease and whether the electrode implanted completely or not. So, the profound sensorineural hearing loss patients after meningitis should be paid more attention. Patients with ossified cochlear could be benefit from cochlear implantation.
18,826,119
[Mass spectrometric analysis of quinazoline alkaloid and limonin from Fructus Evodiae].
To study Mass spectrometry of quinazoline alkaloid and limonin from Fructus Evodiae by an electrospray ionization (ESI) tandem mass spectrometry. The ESI source was set at the positive ionization mode, and the MS1 and MS2 spectra of quinazoline alkaloid and limonin were acquired. The main fragments of quinazoline alkaloid and limonin from Fructus Evodiae were analyzed. The profiles of fragments will be usefull to set quality criteria and to study chemical composition of Fructus Evodiae.
18,826,141
[The study of dynamic acccumulation of camptothecin in Camptotheca acuminata fruit by TLCS].
To establish TLC scanning method for the determination of camptothecin in Camptotheca acuminata fruit, and analysis the dynamic accumulation of camptothecin in Camptotheca acuminata fruit to find out the best collection period. Silica gel H-CMC-Na thin layer plate was adopted in the determination with chloroform-acetone (7 : 3) used as deeloper, Single-wavelength and linear scanning of TLC was used, and the detection wavelength was 360 nm. There was a good linear relationship for Comptothecin within the range of 0.0542 - 0.3252 microg, the average recovery was 97.13%, RSD was 1.76%. The method is accurate, simple and reliable, and can be used for the determination of camptothecin in Camptotheca acuminata fruit and dynamic accumulation research.
18,826,145
[Study on deproteinization and decoloration in extraction of polysaccharides from Rabdosia rubescens].
To screen the method on deproteinization and decoloration in extraction of of polysaccharides from Rabdosia rubescens. The effect of deproteinization with different methods was evaluated in terms of the ratio of protein removing and polysaccharide removing, the decoloration effect was also calculated. The deproteinization effect was optimal with TCA method and activated carbon also achieved a high decoloration rate. The result can establish foundation for the further study of the polysaccharides from Rabdosia rubescens.
18,826,154
Multidimensional LC separations in shotgun proteomics.
Two modes of separation coupled with MS enable researchers to study complicated biological structures.
18,826,178
Design, synthesis, and biological evaluation of novel constrained meta-substituted phenyl propanoic acids as peroxisome proliferator-activated receptor alpha and gamma dual agonists.
In an effort to develop dual PPARalpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPARgamma activators than the lead PPARalpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPARgamma (EC 50 = 0.028 microM) over PPARalpha (EC 50 = 7.22 microM) in vitro and lower blood glucose in db/ db mice more than muraglitazar after oral treatment for 11 days.
18,826,205
Differences between high- and low-affinity complexes of enzymes and nonenzymes.
Physical differences in small molecule binding between enzymes and nonenzymes were found through mining the protein-ligand database, Binding MOAD (Mother of All Databases). The data suggest that divergent approaches may be more productive for improving the affinity of ligands for the two classes of proteins. High-affinity ligands of enzymes are much larger than those with low affinity, indicating that the addition of complementary functional groups is likely to improve the affinity of an enzyme inhibitor. However, this process may not be as fruitful for ligands of nonenzymes. High- and low-affinity ligands of nonenzymes are nearly the same size, so modest modifications and isosteric replacement might be most productive. The inherent differences between enzymes and nonenzymes have significant ramifications for scoring functions and structure-based drug design. In particular, nonenzymes were found to have greater ligand efficiencies than enzymes. Ligand efficiencies are often used to indicate druggability of a target, and this finding supports the feasibility of nonenzymes as drug targets. The differences in ligand efficiencies do not appear to come from the ligands; instead, the pockets yield different amino acid compositions despite very similar distributions of amino acids in the overall protein sequences.
18,826,206
Selective photochemical functionalization of surfactant-dispersed single wall carbon nanotubes in water.
Ultraviolet (UV) irradiation of single wall carbon nanotubes (SWCNTs) individually dispersed in surfactants leads to diameter and type-selective photohydroxylation of the nanotubes. Photohydroxylation of first semiconductor and then small diameter metallic SWCNTs was confirmed after 254 nm UV irradiation in acidic, neutral, and basic aqueous solutions at ambient and elevated temperatures. The increased oxygen content of the SWCNTs after UV irradiation, as detected by X-ray photoelectron spectroscopy, suggests that SWCNTs were hydroxylated by reaction with water. Attenuated total reflectance Fourier transform infrared analysis provides evidence of hydroxyl functional groups on their surface. This photochemical reaction is impeded by molecular oxygen and appears to involve a reactive intermediate generated in the vicinity of semiconducting SWCNTs. This represents a noncontaminating selective reaction in the liquid phase that uses an intrinsic property of the tubes.
18,826,225
Studies on the stereoselective synthesis of C-allyl glycosides.
An investigation was carried out to explore the use of sulfoxide donors as common precursors to stereoisomeric C-glycoconjugates of glycoprotein and glycolipid tumor antigens. A study focusing on the effects of reaction conditions and substrate structure on the stereoselectivity of allylation was carried out. Although conditions were realized to selectively afford alpha-allylation products in good to excellent yields, the search for conditions favoring beta-selectivity proved less successful.
18,826,234
Metalation states versus enzyme activities of Cu, Zn-superoxide dismutase probed by electrospray ionization mass spectrometry.
Cu, Zn-superoxide dismutase (SOD-1), an enzyme that catalyzes the disproportionation reaction of superoxide to produce oxygen and hydrogen peroxide, thereby protecting cells from oxidative stress, is a homodimer that coordinates one copper and one zinc ion per monomer. Cu (2+) and Zn (2+) ions play important roles in enzyme activity and structural stability, respectively. In addition, dimer formation is also essential for fulfilling the function of SOD-1. We here report on the reconstitution and enzyme activities of several metalation states of SOD-1 (Cu 4-, Cu 3Zn-, and Cu 2Zn 2-homodimers). Each metalation state of the reconstituted SOD-1 could be unambiguously differentiated by electrospray ionization mass spectrometry, the metal ions of which had been completely replaced by 99 atom % (63)Cu and (68)Zn stable isotopes. It was found that (1) the Cu 4-dimer possessed 84% of the activity of the native enzyme, (2) the Cu-site resisted being coordinated with Zn (2+) ions while the Zn-site could be bound with Cu (2+) ions, and (3) the simultaneous addition of the Cu (2+) and Zn (2+) ions to generate a fully metalated form produced the multiply metalated SOD-1 (Cu 4-, Cu 3Zn-, and Cu 2Zn 2-dimers), which were clearly distinguishable from one another by the use of the stable isotopes, while the sequential addition of Zn (2+) followed by the Cu (2+) ion predominantly produced a Cu 2Zn 2-dimer comparable to the native enzyme.
18,826,240
Giant magenetoresistive sensors. 2. Detection of biorecognition events at self-referencing and magnetically tagged arrays.
Microfabricated devices formed from alternating layers of magnetic and nonmagnetic materials at combined thicknesses of a few hundred nanometers exhibit a phenomenon known as the giant magnetoresistance effect. Devices based on this effect are known as giant magnetoresistive (GMR) sensors. The resistance of a GMR is dependent on the strength of an external magnetic field, which has resulted in the widespread usage of such platforms in high-speed, high-data density storage drives. The same attributes (i.e., sensitivity, small size, and speed) are also important embodiments of many types of bioanalytical sensors, pointing to an intriguing opportunity via an integration of GMR technology, magnetic labeling strategies, and biorecognition elements (e.g., antibodies). This paper describes the utilization of GMRs for the detection of streptavidin-coated magnetic particles that are selectively captured by biotinylated gold addresses on a 2 x 0.3 cm sample stick. A GMR sensor network reads the addresses on a sample stick in a manner that begins to emulate that of a "card-swipe" system. This study also takes advantage of on-sample magnetic addresses that function as references for internal calibration of the GMR response and as a facile means to account for small variations in the gap between the sample stick and sensor. The magnetic particle surface coverage at the limit of detection was determined to be approximately 2%, which corresponds to approximately 800 binding events over the 200 x 200 microm capture address. These findings, along with the potential use of streptavidin-coated magnetic particles as a universal label for antigen detection in, for example, heterogeneous assays, are discussed.
18,826,241
Mechanistic diversity in the RuBisCO superfamily: a novel isomerization reaction catalyzed by the RuBisCO-like protein from Rhodospirillum rubrum.
Some homologues of D-ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) do not catalyze carboxylation and are designated RuBisCO-like proteins (RLPs). The RLP from Rhodospirillum rubrum (gi:83593333) catalyzes a novel isomerization reaction (overall 1,3-proton transfer reaction; likely, two 1,2-proton transfer reactions) that converts 5-methylthio-D-ribulose 1-phosphate to a 3:1 mixture of 1-methylthioxylulose 5-phosphate and 1-methylthioribulose 5-phosphate. Disruption of the gene encoding the RLP abolishes the ability of R. rubrum to utilize 5'-methylthioadenosine as a sole sulfur source, implicating a new, as-yet-uncharacterized, pathway for sulfur salvage.
18,826,254
Mechanism of H2 production by the [FeFe]H subcluster of di-iron hydrogenases: implications for abiotic catalysts.
To explore the possibility that the active center of the di-iron hydrogenases, the [FeFe] H subcluster, can serve by itself as an efficient hydrogen-producing catalyst, we perform comprehensive calculations of the catalytic properties of the subcluster in vacuo using first principles density functional theory. For completeness, we examine all nine possible geometrical isomers of the Fe(II)Fe(I) active-ready state and report in detail on the relevant ones that lead to the production of H 2. These calculations, carried out at the generalized gradient approximation level, indicate that the most efficient catalytic site in the isolated [FeFe] H subcluster is the Fe d center distal (d) to the [4Fe-4S] H cluster; the other iron center site, the proximal Fe p, also considered in this study, has much higher energy barriers. The pathways with the most favorable kinetics (lowest energy barrier to reaction) proceed along configurations with a CO ligand in a bridging position. The most favorable of these CO-bridging pathways start from isomers where the distal CN (-) ligand is in up position, the vacancy V in down position, and the remaining distal CO is either cis or trans with respect to the proximal CO. These isomers, not observed in the available enzyme X-ray structures, are only marginally less stable than the most stable nonbridging Fe d-CO-terminal isomer. Our calculations indicate that this CO-bridging CN-up isomer has a small barrier to production of H 2 that is compatible with the observed rate for the enzyme. These results suggest that catalysis of H 2 production could proceed on this stereochemically modified [FeFe] H subcluster alone, thus offering a promising target for functional bioinspired catalyst design.
18,826,265
Raman spectroscopic study on the coordination behavior of rare earth ions in N-methylacetamide.
The coordination behavior of rare earth (Ln (3+)) ions in N-methylacetamide (NMA) solution has been investigated at room temperature by Raman spectroscopy. The behavior of the symmetric Raman Ln-Cl stretching (nu Ln-Cl) band, and amide I (nu AI), and III (nu AIII) bands of NMA with the rare earth series is discussed in conjunction with the change in the coordination structure occurring in the middle of the rare earth series. A competition for a coordination equilibria between a Cl (-) ion and an NMA molecule from the rare earth chloride-NMA complex might occur in the middle rare earth region. It is demonstrated that the change in the coordination structure of Ln (3+) ions in NMA is due to an elimination of an NMA molecule.
18,826,268
Synthesis and structure-activity relationship studies of highly potent novel oxazolidinone antibacterials.
Novel antibacterial biaryl oxazolidinones bearing an aza-, an oxa-, or a thiabicyclo[3.1.0]hex-6-yl ring system were synthesized, and their in vitro antibacterial activity and structure-activity relationships (SAR) were evaluated. Most of the synthesized biaryl bicyclo[3.1.0]hex-6-yl oxazolidinones showed good antibacterial activity against the Gram-positive and -negative bacteria tested. Regarding SAR trends among the C-ring subtypes, the pyridyl ring was preferable to the phenyl ring. The results showed that the structural variety of the C-ring has a greater impact on antibacterial activity than that of the B-ring. A cyano group at the D-ring C-6 position plays an important role in the highly potent antibacterial activity.
18,826,297
Strategy for employing unstabilized nucleophiles in palladium-catalyzed asymmetric allylic alkylations.
We report a strategy for the employment of highly unstabilized anions in palladium-catalyzed asymmetric allylic alkylations (AAA). The "hard" 2-methylpyridyl nucleophiles studied are first reacted in situ with BF3.OEt2; subsequent deprotonation of the resulting complexes with LiHMDS affords "soft" anions that are competent nucleophiles in AAA reactions. The reaction is selective for the 2-position of methylpyridines and tolerates bulky aryl and alkyl substitution at the 3-, 4-, and 5-positions. Investigations into the reaction mechanism demonstrate that the configuration of the allylic stereocenter is retained, consistent with the canonical outer sphere mechanism invoked for palladium-catalyzed allylic substitution processes of stabilized anions.
18,826,305
Relationship of "dose" of intracranial hypertension to outcome in severe traumatic brain injury.
It has recently been suggested that the degree of intracranial pressure (ICP) above the treatment goal can be estimated by the area under the curve (AUC) of ICP versus time in patients with severe traumatic brain injury (TBI). The objective of this study was to determine whether the calculated "ICP dose"-the ICP AUC-is related to mortality rate, outcome, and Marshall CT classification. Of 135 patients (age range 1-82 years) with severe TBI treated during a 5-year period at the authors' institution, 113 patients underwent ICP monitoring (84%). Ninety-three patients with a monitoring time>24 hours were included for analysis of ICP AUC calculated using the trapezoidal method. Computed tomography scans were assessed according to the Marshall TBI classification. Patients with Glasgow Outcome Scale scores at 6 months and >3 years were separated into 2 groups based on outcome. Sixty patients (65%) had ICP values>20 mm Hg, and 12 (13%) developed severe intracranial hypertension and died secondary to herniation. A multiple regression analysis adjusting for Glasgow Coma Scale score, age, pupillary abnormalities and Injury Severity Scale score demonstrated that the ICP AUC was a significant predictor of poor outcome at 6 months (p=0.034) and of death (p=0.035). However, it did not predict long-term outcome (p=0.157). The ICP AUC was significantly higher in patients with Marshall head injury Categories 3 and 4 (24 patients) than in those with Category 2 (23 patients, p=0.025) and Category 5 (46 patients, p=0.021) TBIs using the worst CT scan obtained. The authors found a significant relationship between the dose of ICP, the worst Marshall CT score, and patient outcome, suggesting that the AUC method may be useful in refining and improving the treatment of ICP in patients with TBI.
18,826,355
Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma.
Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague-Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5-2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4-10 hours after TBI (p<0.01), lower levels of lactate 6-10 hours after TBI (p<0.01), and lower levels of pyruvate 7.5-10 hours after TBI (p<0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p<0.05). Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.
18,826,359
Risk factors for neurosurgical site infections: an 18-month prospective survey.
The purpose of this study was to determine the incidence rate and risk factors of surgical site infections (SSIs) in neurosurgery for any type of surgery and any American Society of Anesthesiologists class. The authors undertook an exhaustive 18-month prospective survey including patients who underwent neurosurgery. In particular, a 30-day follow-up was completed in patients whose surgery did not involve placement of a prosthesis or implant, and 1-year follow-up was completed for patients who underwent surgery to place a prosthesis or implant. The Centers for Disease Control definition of SSI was used. Univariate and multivariate analyses were conducted; all dependent variables found in univariate analysis were entered in the multiple regression model. A stepwise multiple logistic regression method was used. Of the 844 patients studied, 35 SSIs were diagnosed, yielding an incidence rate of 4.1% (95% confidence interval 3.6-4.5). Independent predictive risk factors for infection were cerebrospinal fluid leakage, external shunt, Altemeier class, and further neurosurgery. A lack of antibiotic prophylaxis was not found to be a risk factor. Infection risk factors occur mainly during the postoperative period.
18,826,362
Reduction of the immune response to factor VIII mediated through tolerogenic factor VIII presentation by immature dendritic cells.
The development of neutralizing antibodies to factor FVIII (FVIII) represents the most serious complication in the treatment of hemophilia A. We have explored the potential of using immature dendritic cells (iDCs) to present FVIII in a tolerogenic manner to T cells. The iDCs were isolated from hemophilic murine bone marrow and pulsed with canine cFVIII (cFVIII-iDCs) in the presence or absence of the NFkappaB pathway blocking compound Andrographolide (Andro-cFVIII-iDCs). Three weekly intravenous infusions of one million cFVIII pulsed-iDCs were administered to a group of five hemophilic Balb/c mice. Anti-FVIII antibody levels were monitored by functional Bethesda assay after four weekly intravenous challenges with 2 IU of cFVIII. We have shown that cFVIII in the presence or absence of Andro is efficiently taken up by iDCs and that this process does not result in the maturation of DCs or the activation of co-cultured T cells. Following repeated infusion of the cFVIII-iDCs and Andro-cFVIII-iDCs into hemophilic mice, which were subsequently challenged with cFVIII, long-term reductions of FVIII inhibitors of 25% and 40%, respectively, were documented. Studies of cytokine release and T-cell phenotypes indicate that the mechanisms responsible for reducing immunologic responsiveness to cFVIII appear to involve an expansion of Foxp3 T regulatory cells in the case of cFVIII-iDC infusion and the elaboration of the immunosuppressive cytokines IL-10 and TGF-beta following andrographolide-treated cFVIII-iDCs. This study shows that tolerogenic presentation of cFVIII to the immune system can significantly reduce immunogenicity of the protein.
18,826,393
Ferritins control interaction between iron homeostasis and oxidative stress in Arabidopsis.
Ferritin protein nanocages are the main iron store in mammals. They have been predicted to fulfil the same function in plants but direct evidence was lacking. To address this, a loss-of-function approach was developed in Arabidopsis. We present evidence that ferritins do not constitute the major iron pool either in seeds for seedling development or in leaves for proper functioning of the photosynthetic apparatus. Loss of ferritins in vegetative and reproductive organs resulted in sensitivity to excess iron, as shown by reduced growth and strong defects in flower development. Furthermore, the absence of ferritin led to a strong deregulation of expression of several metal transporters genes in the stalk, over-accumulation of iron in reproductive organs, and a decrease in fertility. Finally, we show that, in the absence of ferritin, plants have higher levels of reactive oxygen species, and increased activity of enzymes involved in their detoxification. Seed germination also showed higher sensitivity to pro-oxidant treatments. Arabidopsis ferritins are therefore essential to protect cells against oxidative damage.
18,826,427
Reverse dissimilatory sulfite reductase as phylogenetic marker for a subgroup of sulfur-oxidizing prokaryotes.
Sulfur-oxidizing prokaryotes (SOP) catalyse a central step in the global S-cycle and are of major functional importance for a variety of natural and engineered systems, but our knowledge on their actual diversity and environmental distribution patterns is still rather limited. In this study we developed a specific PCR assay for the detection of dsrAB that encode the reversely operating sirohaem dissimilatory sulfite reductase (rDSR) and are present in many but not all published genomes of SOP. The PCR assay was used to screen 42 strains of SOP (most without published genome sequence) representing the recognized diversity of this guild. For 13 of these strains dsrAB was detected and the respective PCR product was sequenced. Interestingly, most dsrAB-encoding SOP are capable of forming sulfur storage compounds. Phylogenetic analysis demonstrated largely congruent rDSR and 16S rRNA consensus tree topologies, indicating that lateral transfer events did not play an important role in the evolutionary history of known rDSR. Thus, this enzyme represents a suitable phylogenetic marker for diversity analyses of sulfur storage compound-exploiting SOP in the environment. The potential of this new functional gene approach was demonstrated by comparative sequence analyses of all dsrAB present in published metagenomes and by applying it for a SOP census in selected marine worms and an alkaline lake sediment.
18,826,437
Should glycemic index and glycemic load be considered in dietary recommendations?
High glycemic index (GI) and glycemic load (GL) have been proposed to be associated with increased risk of lifestyle diseases. Since protein intake varies little in humans, adherence to the common recommendation to reduce fat intake probably leads to increases in carbohydrate intake, which emphasizes the need to investigate the effects of carbohydrate on diet-related conditions and diseases. This review examines the epidemiological literature linking GI and GL to heart disease, insulin sensitivity, type 2 diabetes, dyslipidemia, and obesity among initially healthy people. The evidence for associations between GI and particularly GL and health among free-living populations is mixed. Only the positive association between GI and development of type 2 diabetes was consistent across cross-sectional and longitudinal studies for both sexes. Low GI/GL may protect against heart disease in women, and cross-sectional studies indicate low GI/GL may reduce high-density-lipoprotein cholesterol and triacylglycerol levels in both sexes. Based on the evidence found in this review, it seems premature to include GI/GL in dietary recommendations.
18,826,453
Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases.
Studies show that the plant polyphenol resveratrol can extend the life span of yeast, worms, flies, and fish. It also mitigates the metabolic dysfunction of mice fed high-fat diets. Resveratrol appears to mediate these effects partly by activating SIRT1, a deacetylase enzyme that regulates the activity of several transcriptional factors and enzymes responsive to nutrient availability. However, few foods contain resveratrol and humans metabolize it extensively, resulting in very low systemic bioavailability. Substantial research effort now focuses on identifying and testing more bioavailable and potent activators of SIRT1 for use as pharmacologic interventions in aging and age-related disorders.
18,826,454
Comparability between telephone and face-to-face structured clinical interview for DSM-IV in assessing social anxiety disorder.
This article evaluates the comparability of the telephone and in-person Structured Clinical Interview for DSM-IV (SCID) interviews in assessing patients with social anxiety disorder (SAD) as an independent anxiety diagnosis. One hundred subjects were randomly selected and interviewed with the SCID, once by telephone and once in person (1-3 months later). The prevalence of SAD assessed with the telephone interviews was 56%, whereas the in-person prevalence was 52%, with no statistically significant difference. The test-retest kappa for the 200 interviews was .84, indication of excellent agreement. These findings, along with the existing evidence of their validity, should encourage the use of SCID by telephone for SAD diagnostic interviews.
18,826,462
Cytokines and their role in depression.
This study aims to review the cytokines that mediate the inflammatory process, the interleukins and the interferons, and the interaction of cytokines with serotonin as causative factors in the role of depression. Administration of proinflammatory cytokines to treat medical diseases induces depressive symptoms in humans. Patients diagnosed with depression tend to have high levels of cytokine activity and impaired immune response, as well as those patients suffering from inflammatory processes. Proinflammatory cytokines interfere with the body's feedback loop to reduce circulating corticosteroids during the stress response. Serotonin levels, integrally associated with depression, are lowered when levels of circulating cytokines are high when the precursor tryptophan is reduced.
18,826,467
Infants' use of lexical-category-to-meaning links in object individuation.
Infants watched an experimenter retrieve a stuffed animal from an opaque box and then return it. This happened twice, consistent with either 1 animal appearing on 2 occasions or 2 identical-looking animals each appearing once. The experimenter labeled each object appearance with a different novel label. After infants retrieved 1 object from the box, their subsequent search behavior was recorded. Twenty-month-olds, but not 16-month-olds, searched significantly longer for a second object inside the box when the labels were both proper names than when they were 1 count noun followed by 1 proper name. The effect was not significant when proper names were replaced by adjectives. Twenty-month-olds' understanding of meaning distinctions among several word categories guided their object individuation.
18,826,534
Perception of dynamic and static audiovisual sequences in 3- and 4-month-old infants.
This study investigated perception of audiovisual sequences in 3- and 4-month-old infants. Infants were habituated to sequences consisting of moving/sounding or looming/sounding objects and then tested for their ability to detect changes in the order of the objects, sounds, or both. Results showed that 3-month-olds perceived the order of 3-element sequences and that 4-month-olds perceived the order of 3- and 4-element sequences. In addition, results indicated that perception of moving sequences was more robust than of looming ones and that detection of order differences was not based on primacy cues. The current results show that perception of multisensory sequences and their structure emerges early in development, and a preliminary model of the development of sequence perception is offered.
18,826,541
Low grade papillary transitional cell carcinoma pelvic recurrence masquerading as high grade invasive carcinoma, ten years after radical cystectomy.
Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not been reported previously. We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up. A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed.
18,826,578
Harnessing the wealth of Chinese scientific literature: schistosomiasis research and control in China.
The economy of China continues to boom and so have its biomedical research and related publishing activities. Several so-called neglected tropical diseases that are most common in the developing world are still rampant or even emerging in some parts of China. The purpose of this article is to document the significant research potential from the Chinese biomedical bibliographic databases. The research contributions from China in the epidemiology and control of schistosomiasis provide an excellent illustration. We searched two widely used databases, namely China National Knowledge Infrastructure (CNKI) and VIP Information (VIP). Employing the keyword "Schistosoma" and covering the period 1990-2006, we obtained 10,244 hits in the CNKI database and 5,975 in VIP. We examined 10 Chinese biomedical journals that published the highest number of original research articles on schistosomiasis for issues including languages and open access. Although most of the journals are published in Chinese, English abstracts are usually available. Open access to full articles was available in China Tropical Medicine in 2005/2006 and is granted by the Chinese Journal of Parasitology and Parasitic Diseases since 2003; none of the other journals examined offered open access. We reviewed (i) the discovery and development of antischistosomal drugs, (ii) the progress made with molluscicides and (iii) environmental management for schistosomiasis control in China over the past 20 years. In conclusion, significant research is published in the Chinese literature, which is relevant for local control measures and global scientific knowledge. Open access should be encouraged and language barriers removed so the wealth of Chinese research can be more fully appreciated by the scientific community.
18,826,598
The relationship between depressive symptoms, health service consumption, and prognosis after acute myocardial infarction: a prospective cohort study.
The use of cardiovascular health services is greater among patients with depressive symptoms than among patients without. However, the extent to which such associations between depressive symptoms and health service utilization are attributable to variations in comorbidity and prognostic disease severity is unknown. This paper explores the relationship between depressive symptoms, health service cardiovascular consumption, and prognosis following acute myocardial infarction (AMI). The study design was a prospective cohort study with follow-up telephone interviews of 1,941 patients 30 days following AMI discharged from 53 hospitals across Ontario, Canada between December 1999 and February, 2003. Outcome measures were post discharge use of cardiac and non-cardiac health care services. The service utilization outcomes were adjusted for age, sex, income, comorbidity, two validated measures of prognosis (cardiac functional capacity and risk adjustment severity index), cardiac procedures (CABG or PTCA) and drugs prescribed at discharge. Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19-1.30, P < 0.001), 9% (Adjusted RR:1.09; 95% CI:1.02-1.16, P = 0.007) and 43% (Adjusted RR: 1.43; 95% CI:1.34-1.52, P < 0.001) increase in total, cardiac, and non-cardiac hospitalization days post-AMI respectively, after adjusting for baseline patient and hospital characteristics. Depressive-associated increases in cardiac health service consumption were significantly more pronounced among patients of lower than higher cardiac risk severity. Depressive symptoms were not associated with increased mortality after adjusting for baseline patient characteristics. Depressive symptoms are associated with significantly higher cardiac and non-cardiac health service consumption following AMI despite adjustments for comorbidity and prognostic severity. The disproportionately higher cardiac health service consumption among lower-risk AMI depressive patients may suggest that health seeking behaviors are mediated by psychosocial factors more so than by objective measures of cardiovascular risk or necessity.
18,826,611
Posterior mediastinal melanoma causing severe dysphagia: a case report.
We describe an original case of progressive severe dysphagia caused by a posterior mediastinal metastatic melanoma of unknown origin. To the best of our knowledge, such an event has never been described before in the literature. A progressive severe dysphagia case is reported induced by a melanoma of unknown origin (metastatic to a posterior mediastinal lymph node). At the time of diagnosis, the lesion appeared as a large posterior mediastinal mass mimicking a neurogenic tumour with oesophageal involvement. After complete resection, pathological assessment of the tumour by immunohistochemistry was consistent with nodal metastatic melanoma. This report of a posterior mediastinal lymph node melanoma is unique. The nodal origin is definitely unusual: a primary melanoma should always be carefully ruled out. In fact no other evidence, a part from the absence of the tumour elsewhere, can support the diagnosis of a primary nodal melanoma.
18,826,613
Carbon fluxes resulting from land-use changes in the Tamaulipan thornscrub of northeastern Mexico.
Information on carbon stock and flux resulting from land-use changes in subtropical, semi-arid ecosystems are important to understand global carbon flux, yet little data is available. In the Tamaulipan thornscrub forests of northeastern Mexico, biomass components of standing vegetation were estimated from 56 quadrats (200 m2 each). Regional land-use changes and present forest cover, as well as estimates of soil organic carbon from chronosequences, were used to predict carbon stocks and fluxes in this ecosystem.For the period of 1980-1996, the Tamaulipan thornscrub is presenting an annual deforestation rate of 2.27% indicating that approximately 600 km2 of this plant community are lost every year and that 60% of the original Mexican Tamaulipan thornscrub vegetation has been lost since the 1950's. On the other hand, intensive agriculture, including introduced grasslands increased (4,000 km2) from 32 to 42% of the total studied area, largely at the expense of the Tamaulipan thornscrub forests. Land-use changes from Tamaulipan thornscrub forest to agriculture contribute 2.2 Tg to current annual carbon emissions and standing biomass averages 0.24 +/- 0.06 Tg, root biomass averages 0.17 +/- 0.03 Tg, and soil organic carbon averages 1.80 +/- 0.27 Tg. Land-use changes from 1950 to 2000 accounted for Carbon emissions of the order of 180.1 Tg. Projected land-use changes will likely contribute to an additional carbon flux of 98.0 Tg by the year 2100. Practices to conserve sequester, and transfer carbon stocks in semi-arid ecosystems are discussed as a means to reduce carbon flux from deforestation practices.
18,826,617
An efficient method for visualization and growth of fluorescent Xanthomonas oryzae pv. oryzae in planta.
Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight disease, is a serious pathogen of rice. Here we describe a fluorescent marker system to study virulence and pathogenicity of X. oryzae pv. oryzae. A fluorescent X. oryzae pv. oryzae Philippine race 6 strain expressing green fluorescent protein (GFP) (PXO99GFP) was generated using the gfp gene under the control of the neomycin promoter in the vector, pPneo-gfp. The PXO99GFPstrain displayed identical virulence and avirulence properties as the wild type control strain, PXO99. Using fluorescent microscopy, bacterial multiplication and colonization were directly observed in rice xylem vessels. Accurate and rapid determination of bacterial growth was assessed using fluoremetry and an Enzyme-Linked ImmunoSorbant Assay (ELISA). Our results indicate that the fluorescent marker system is useful for assessing bacterial infection and monitoring bacterial multiplication in planta.
18,826,644
Linkage disequilibrium compared between five populations of domestic sheep.
The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed. Short range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used. Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.
18,826,649
Ethnomedicinal plant use by Lepcha tribe of Dzongu valley, bordering Khangchendzonga Biosphere Reserve, in North Sikkim, India.
Lepcha is the oldest and the first tribe reported from Sikkim, India; majority of its population inhabiting in Dzongu valley, an officially demarcated reserve for Lepcha community, bordering Khangchendzonga Biosphere Reserve, in north district. Lepchas of Dzongu are known for their retention of rich cultural heritage. In view of the on-going cultural and economic changes brought in by the process of globalization, the immediate need was felt to document in details the under-explored ethnomedicinal practices of Lepchas of Dzongu valley. This paper reports 118 species, belonging to 71 families and 108 genera, under ethnomedicinal utility by the Lepchas for curing approximately 66 ailments, which could be grouped under 14 broad categories. Zingiberaceae appeared as the most used family (8 species and 5 genera). As per use pattern, maximum of 30.50% species are to cure stomach related disorders/ailments, followed by 19.49% for curing cut, wounds, inflammation, sprains and joint pains. Administration of medicine orally is recorded in 75% cases. Root and rhizome harvesting targeted 30 species. The changing scenario over time both at socio-cultural front and passing traditional knowledge interests from older to younger generation and rich ethnomicinal wealth of the oldest tribe of Sikkim are discussed in the light of conservation strategies and techniques to adopt.
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Ultrasound-guided core needle biopsy of parotid gland swellings.
To determine whether ultrasound-guided core needle biopsy is a safe and reliable investigation in cases of parotid swelling in which fine needle aspiration cytology has failed to give a definitive diagnosis. Analysis of 66 ultrasound-guided core biopsy specimens of the parotid gland (the largest series reported thus far) sample number refers to histological samples throughout the paper. All the 184 cases of parotid surgery with a histological diagnosis were included. The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology and ultrasound-guided core needle biopsy, as compared with the final histological analysis. Of a total of 184 patients, 89.1 per cent (164/184) had benign parotid lesions excised. The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology for benign lesions were 76.2, 84.2 and 87.5 per cent, respectively, and those of ultrasound-guided core needle biopsy were 91.7, 98.2 and 96.4 per cent, respectively. Twenty of 184 patients (10.9 per cent) had malignant lesions. The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology for detection of malignant lesions were 60, 75 and 75 per cent, respectively, while those of ultrasound-guided core biopsy were 89, 100 and 100 per cent, respectively. Non-diagnostic rates were 25.8 per cent for fine needle aspiration cytology and 4.5 per cent for ultrasound-guided core biopsy. Only one case of complications (a sub-clinical haematoma) occurred in the ultrasound-guided core biopsy group. We propose ultrasound-guided core needle biopsy as a very safe and effective tool in cases of parotid swelling in which fine needle aspiration cytology has failed to give a definitive diagnosis.
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ALaRMED: adverse events in low-risk chest pain patients receiving continuous ECG monitoring in the emergency department: a survey of Canadian emergency physicians.
Current guidelines suggest that most patients who present to an emergency department (ED) with chest pain should be placed on a continuous electrocardiographic monitoring (CEM) device. We surveyed emergency physicians to determine their perception of current occupancy rates of CEM and to assess their attitudes toward prescribing monitors for low-risk chest pain patients in the ED. We conducted a cross-sectional, self-administered Internet and mail survey of a random sample of 300 members of the Canadian Association of Emergency Physicians. Main outcome measures included the perceived frequency of fully occupied monitors in the ED and physicians' willingness to forgo CEM in certain chest pain patients. The response rate was 66% (199 respondents). The largest group of respondents (43%; 95% confidence interval [CI] 36%-50%) indicated that monitors were fully occupied 90%-100% of the time during their most recent ED shift. When asked how often they were forced to choose a patient for monitor removal because of the limited number of monitors, 52% (95% CI 45%-60%) of respondents selected 1-3 times per shift. Ninety percent (95% CI 84%-93%) of respondents indicated that they would forgo CEM in certain cardiac chest pain patients if there was good evidence that the risk of a monitor-detected adverse event was very low. Emergency physicians report that monitors are often fully occupied in Canadian EDs, and most are willing to forgo CEM in certain chest pain patients. A large prospective study of CEM in low-risk chest pain patients is warranted.
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Matrix metalloproteinases in intracerebral hemorrhage.
The objective of this study is to review the role of matrix metalloproteinases in intracerebral hemorrhage, which is associated with hypertension, head trauma and premature birth. A PubMed search of literature pertaining to this study was conducted in April 2008 using specific keyword search terms pertaining to intracerebral hemorrhage and matrix metalloproteinases. Some papers are not cited here as it is not possible to be all inclusive or due to the space limit from the journal. The prognosis following ICH is more detrimental than that of ischemic strokes. Matrix metalloproteases have been implicated in the pathogenesis of brain damage following ICH. The goal of this review is to bring together recent diverse data concerning the roles of matrix metalloproteinases after intracerebral hemorrhage, which includes the role of matrix metalloproteinases in central nervous system, matrix metalloproteinases in animal models and humans of intracerebral hemorrhage, the relationship between matrix metalloproteinases and neuroinflammation, neuronal death, blood-brain barrier disruption and interaction with other molecules, as well as treatment of intracerebral hemorrhage with anti-matrix metalloproteinases agents. Besides deleterious roles in the acute period of intracerebral hemorrhage, some matrix metalloproteinases function in the later stages following intracerebral hemorrhage may have beneficial remodeling activity. At present, the experimental data support the use of pharmacologic anti-matrix metalloproteinases strategies in the acute periods following intracerebral hemorrhage to alleviate injury.
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New hosts for equine herpesvirus 9.
Equine herpesvirus 9 was detected in a polar bear with progressive encephalitis; the source was traced to 2 members of a potential equid reservoir species, Grevy's zebras. The virus was also found in an aborted Persian onager. Thus, the natural host range is extended to 6 species in 3 mammalian orders.
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Extended sequence typing of Campylobacter spp., United Kingdom.
Supplementing Campylobacter spp. multilocus sequence typing with nucleotide sequence typing of 3 antigen genes increased the discriminatory index achieved from 0.975 to 0.992 among 620 clinical isolates from Oxfordshire, United Kingdom. This enhanced typing scheme enabled identification of clusters and retained data required for long-range epidemiologic comparisons of isolates.
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Effect of HMG CoA reductase inhibitors on low-density lipoprotein cholesterol and C-reactive protein: systematic review and meta-analysis.
HMG CoA reductase inhibitors (statins) have been claimed to decrease C-reactive protein (CRP), independent of their effect on low-density lipoprotein cholesterol (LDL-C). We conducted a systematic review and meta-analysis to investigate whether a relationship between the average effect of statins on LDL-C and CRP exists. The literature search of the Medline and Cochrane databases between 1980 and August 2007 yielded 65 statin intervention studies with 94 treatment arms involving 16,260 patients reporting changes in both LDL-C and CRP. DATA EXTRACTION AND STATISTICAL METHOD: From each study relative changes in LDL-C and CRP were extracted. Random effects meta-analysis was used to obtain pooled summary estimates of the average study specific LDL-C and CRP reductions, in total and stratified by dose and type of statin. Weighted correlation analysis and metaregression analysis was used to investigate the relationship between the LDL-C and CRP changes adjusted for baseline values, type of statin and dose. Pooled summary estimates of statin-induced changes in LDL-C and CRP levels were -34.7% (95% CI: -37.7% to -31.8%) and -30.8% (95% CI: -39.4% to -22.3%), respectively. We found a positive correlation between the average LDL-C and CRP reduction (r = 0.49, p = 0.010) which increased when adjusting for pre-treatment concentrations (r = 0.79, p < 0.001). The effect of statins on CRP were strongly related to the changes in LDL-C and baseline concentrations, independent of the type and dose of statin used. Our meta-analysis shows a strong correlation between statin-induced reductions in LDL-C and CRP, which has not been evident from individual studies. Measuring CRP in addition to LDL-C in the monitoring of statin treatment is currently not warranted.
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Influence of grape juice and orange juice on the pharmacokinetics and pharmacodynamics of diltiazem in healthy human male subjects.
The objective was to study the effect of grape juice and orange juice on the pharmacokinetics (PK) and pharmacodynamics (PD) of diltiazem in healthy human volunteers. The study design was open-label, balanced, randomized, 3-period, single-dose and crossover. A group of 12 healthy, adult, male human volunteers received a single oral dose of diltiazem 180 mg extended release capsule on three different occasions: with 200 ml of water, with 200 ml of grape juice and with 200 ml of orange juice in random order. A washout period of 7 days was kept between each study period. Serial blood samples were collected up to 24 h post dose and assayed for diltiazem using a specific and validated HPLC method. Blood pressure (BP) and ECG measurements were done at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h post dose. Analysis of variance was carried out using logarithmic transformations of AUC and Cmax as well as nontransformed tmax. No significant change was observed in heart rate and BP. The median tmax was identical in all three occasions. The 90% CI of the Cmax ratios for orange juice/water were 104.59 - 114.86 and for grape juice/water were 93.91 - 103.13. Similarly, the 90% CI of the AUC0-inf ratios for orange juice and grape juice vs. water were 103.68 - 119.83 and 88.56 - 104.06, respectively. Since these values fall within the bioequivalence criteria of 80 - 120% limits, our study demonstrates absence of interaction of diltiazem with grape juice or orange juice. There is no significant influence of grape juice or orange juice on the pharmacokinetics and pharmacodynamics of diltiazem.
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Perceptions of Medicare Part D enrollees about pharmacists and their role as providers of medication therapy management.
To explore the awareness of Medicare Part D enrollees regarding medication therapy management (MTM) and to examine their expectations and perceptions of pharmacists in providing MTM. The Internet-based survey consisted of questions on respondent demographics, prescription-related behavior, awareness of MTM, and expectation and perception of pharmacists in usual roles and as MTM providers. Four open-ended questions examined expectations, trust, source of MTM information, and perceived benefit from MTM. The sample of 504 Medicare Part D enrollees from California (mean age 72 years) used an average of 4.3 prescriptions per day. Awareness of MTM was low in this cohort (93% unaware). Trust in the pharmacist was centered on dispensing prescriptions. Expectation of pharmacists also revolved around product (>60%). Approximately 70% of respondents did not believe they needed MTM; however, 58% believed pharmacists were good candidates to provide MTM. Willingness to pay for MTM services was also low (31%). Medicare Part D enrollees' expectation and perception of pharmacists revolves around the dispensing function. The public, payers, and policy makers need to be educated to recognize and use pharmacists as cost-effective providers of MTM.
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Columbus Air Force Base medication profile intervention practice innovation.
To determine whether community pharmacist-initiated interventions containing a recommendation to adjust prescribed medication therapy and delivered via fax are viewed as helpful by prescribers and to what extent prescribers accept those recommendations. Cross-sectional. Columbus Air Force Base (Columbus, MS) during a 3-month period in August through October 2007. 57 patient profiles were reviewed by pharmacy staff. Pharmacy staff evaluated patient profiles with eight or more active medications for drug interactions, therapeutic duplications, ability to simplify complex drug regimens, and opportunities for additional therapy. After reviewing a patient profile, the pharmacist completed a medication management report, noted any recommendations about medication therapy, and faxed the report to the patient's primary care provider. Physicians were asked to return a form detailing their response to the medication management report. Whether pharmacist recommendations were deemed helpful by prescribers in making clinical decisions. Secondary outcome measures included the degree to which prescribers accepted pharmacist recommendations and how quickly providers responded to pharmacist recommendations. The pharmacist-initiated medication management fax had a 64.9% response rate from prescribers and was considered helpful by 97.3% of prescribers who returned the form to the pharmacist. In addition, the majority of prescribers stated via the form that they would address the pharmacist's concerns at the next patient visit or call and schedule an appointment with the patient. As this initiative continues and grows, prescribers will be more aware of the medication management fax form program and, theoretically, will be more likely to respond to pharmacist recommendations.
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Reliability testing of a case-leveling framework for assigning level of difficulty of pharmacist's initial patient medication assessments.
To develop and test the reliability of a case-leveling framework for assigning level of difficulty of the pharmacist's task for initial medication assessments conducted by pharmacists integrated into family physician offices. Descriptive study. Seven family practice sites in Ontario from June 2004 to July 2006. Patients referred by their family physician for pharmacist assessment. Individual medication assessments, monitoring, and follow-up by pharmacists. A case-leveling framework was developed with three levels of complexity (graded as I, II, or III) including specific descriptors and practice-based examples. Reliability was assessed between two standardized assessors and between one assessor and project pharmacists. Project pharmacist feedback was elicited through an e-mail survey. Reliability is reported using the kappa statistic. Reliability of a case-leveling framework and helpfulness of the framework as reported by pharmacists. 53 patient cases were evaluated for interrater reliability between standardized assessors. The mean (+/- SD) case level assigned was 1.8 +/- 0.68, and the kappa was 0.62 (95% CI 0.44-0.79), indicating a substantial strength of agreement between raters. For the second reliability test, 52 cases were rated, with a level of agreement between project pharmacists and the external assessor of 0.46 (95% CI 0.27-0.65), indicating moderate agreement. Feedback resulted in slight revisions to the original framework. The case-leveling framework was a reliable method and can be used to determine the level of difficulty of patient cases in primary care.
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Early differentiation of the Earth and the Moon.
We examine the implications of new 182W and 142Nd data for Mars and the Moon for the early evolution of the Earth. The similarity of 182W in the terrestrial and lunar mantles and their apparently differing Hf/W ratios indicate that the Moon-forming giant impact most probably took place more than 60Ma after the formation of calcium-aluminium-rich inclusions (4.568Gyr). This is not inconsistent with the apparent U-Pb age of the Earth. The new 142Nd data for Martian meteorites show that Mars probably has a super-chondritic Sm/Nd that could coincide with that of the Earth and the Moon. If this is interpreted by an early mantle differentiation event, this requires a buried enriched reservoir for the three objects. This is highly unlikely. For the Earth, we show, based on new mass-balance calculations for Nd isotopes, that the presence of a hidden reservoir is difficult to reconcile with the combined 142Nd-143Nd systematics of the Earth's mantle. We argue that a likely possibility is that the missing component was lost during or prior to accretion. Furthermore, the 142Nd data for the Moon that were used to argue for the solidification of the magma ocean at ca 200Myr are reinterpreted. Cumulate overturn, magma mixing and melting following lunar magma ocean crystallization at 50-100Myr could have yielded the 200Myr model age.
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Accretion of the Earth.
The origin of the Earth and its Moon has been the focus of an enormous body of research. In this paper I review some of the current models of terrestrial planet accretion, and discuss assumptions common to most works that may require re-examination. Density-wave interactions between growing planets and the gas nebula may help to explain the current near-circular orbits of the Earth and Venus, and may result in large-scale radial migration of proto-planetary embryos. Migration would weaken the link between the present locations of the planets and the original provenance of the material that formed them. Fragmentation can potentially lead to faster accretion and could also damp final planet orbital eccentricities. The Moon-forming impact is believed to be the final major event in the Earth's accretion. Successful simulations of lunar-forming impacts involve a differentiated impactor containing between 0.1 and 0.2 Earth masses, an impact angle near 45 degrees and an impact speed within 10 per cent of the Earth's escape velocity. All successful impacts-with or without pre-impact rotation-imply that the Moon formed primarily from material originating from the impactor rather than from the proto-Earth. This must ultimately be reconciled with compositional similarities between the Earth and the Moon.
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Genomic evidence for a large-Z effect.
The 'large-X effect' suggests that sex chromosomes play a disproportionate role in adaptive evolution. Theoretical work indicates that this effect may be most pronounced in genetic systems with female heterogamety under both good-genes and Fisher's runaway models of sexual selection (males ZZ, females ZW). Here, I use a comparative genomic approach (alignments of several thousands of chicken-zebra finch-human-mouse-opossum orthologues) to show that avian Z-linked genes are highly overrepresented among those bird-mammalian orthologues that show evidence of accelerated rate of functional evolution in birds relative to mammals; the data suggest a twofold excess of such genes on the Z chromosome. A reciprocal analysis of genes accelerated in mammals found no evidence for an excess of X-linkage. This would be compatible with theoretical expectations for differential selection on sex-linked genes under male and female heterogamety, although the power in this case was not sufficient to statistically show that 'large-Z' was more pronounced than 'large-X'. Accelerated Z-linked genes include a variety of functional categories and are characterized by higher non-synonymous to synonymous substitution rate ratios than both accelerated autosomal and non-accelerated genes. This points at a genomic 'large-Z effect', which is widespread and of general significance for adaptive divergence in birds.
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Between-group competition and human cooperation.
A distinctive feature of human behaviour is the widespread occurrence of cooperation among unrelated individuals. Explaining the maintenance of costly within-group cooperation is a challenge because the incentive to free ride on the efforts of other group members is expected to lead to decay of cooperation. However, the costs of cooperation can be diminished or overcome when there is competition at a higher level of organizational hierarchy. Here we show that competition between groups resolves the paradigmatic 'public goods' social dilemma and increases within-group cooperation and overall productivity. Further, group competition intensifies the moral emotions of anger and guilt associated with violations of the cooperative norm. The results suggest an important role for group conflict in the evolution of human cooperation and moral emotions.
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