The impact of urine on the microbial biomass, activity and community structure was compared in the soil beneath two pastures in the Scottish uplands; Fasset, a natural Agrostis capillaris-Festuca ...ovina-Galium saxatile grassland and Strathfinella, a semi-natural grassland, improved with fertiliser addition. Community level physiological profiles (CLPP) were used to characterise the microbial communities. The utilisation of sugars, oligosaccharides, alcohols, carboxylic acids, long chain aliphatic acids, acidic, basic and neutral amino acids, amide N, phenolic acids and long chain aliphatic acids was used to compare the soils and the impact of synthetic urine addition. In the untreated soils, the utilisation of all the substrates decreased from the first week in May through to October. Averaged over all times and urine treatment, the potential utilisation of all substrates except for phenolic acids, long chain aliphatic acids and carboxylic acids was greater in the improved and more intensively grazed Strathfinella site. When averaged over all sample times, urine increased the utilisation of sugars, oligosaccharides, basic amino acids and amide N and the increases were greater in the unimproved, less intensively grazed, Fasset soil than that at Strathfinella. The effect of urine tended to be greatest during the period between 2 and 5 weeks after urine addition when utilisation of alcohols, acidic and neutral amino acids was also increased. Microbial biomass C in the control soils was 155.9 and 112.7 g C m⁻² at Fasset and Strathfinella, respectively. Values did not change significantly with time and were unchanged by the addition of urine. However, urine addition significantly increased basal respiration rates at Fasset and decreased them at Strathfinella. Urine also increased bacterial numbers in both soils, but had no consistent effect on fungi or yeasts. The significance of these findings for studies of soil microbial community structure and activity in grazed upland grasslands is discussed.
Recently there has been an increase in the number of deaths in the United States caused due to overdose of nonpharmaceutical Fentanyl among illicit drug users. To try and prevent this, public health ...agencies have formed task forces and intensified community outreach to drug users.
We examined the C-reactive protein (CRP) response after spontaneous intracerebral hemorrhage (sICH) and its relationship to outcome. We additionally characterized early brain localization of CRP.
In ...this prospective, multicenter, international, collaborative, longitudinal study with cross-sectional immunohistochemical analysis of brain tissue, 223 patients (M/F: 132/91) were recruited during the 2010 calendar year. CRP was evaluated at admission (median 93 minutes from symptom onset), 24 hours, 48 hours, and 72 hours after sICH. Brains of 5 subjects with sICH were compared to brains of 2 aged controls without evidence of brain pathology and 7 patients with ischemic stroke. Plasma CRP was measured over 72 hours following sICH and its relationship to 30-day mortality and functional outcome at 30 days (Glasgow Outcome Scale) was determined. CRP immunostaining patterns were analyzed in samples of sICH autopsy brains.
Plasma CRP increased over the 48 hours from admission and was significantly (p < 0.001) related to hematoma volume at later time points. The predictive utility of CRP for morbidity and mortality were maintained when adjusted for other risk factors and improved at 48 hours and 72 hours when compared with admission values. Although an early CRP localization was present in both ischemic and hemorrhagic lesions, an intense and diffuse neuropil staining was only present in sICH patients and particularly evident proximal to the hemorrhagic areas.
Plasma CRP production increases markedly over the 48 hours to 72 hours period following sICH and is related to outcome. CRP is also present in large amounts around the hemorrhagic lesion and within neurons and glia of patients who died within 12 hours of sICH.
Abstract only
2004
Background: Vorinostat is a histone deacetylase inhibitor that represents a rational therapeutic target in GBM. Methods: Recurrent GBM patients (pts) having received = 1 prior ...chemo regimen for progressive disease were eligible. Vorinostat dose was 200 mg bid x 14 days q 3 weeks. We applied a phase II design which had 90% power to declare the regimen active if the study PFS6 rate was 25%, a 15% rate increase over PFS6 in historical controls (10%). Results: 68 patients were treated. Grade 3+ non-hematologic toxicity consisting mainly of fatigue, diarrhea and dehydration occurred in 23% of pts; Grade 3+ hematologic toxicity consisting mainly of thrombocytopenia occurred in 25% of pts. Intra-patient dose escalation to 300 mg bid resulted in higher incidence of grade 3+ thrombocytopenia (45%) and was aborted. Pts receiving enzyme-inducing anticonvulsants (EIAC) had significantly less grade 3 + non-hematologic toxicity (p=0.01) and grade 3/4 thrombocytopenia (p=0.04). Pharmacokinetic analysis showed lower vorninostat C-max and AUC (0–24h) values and higher vorinostat-glucuronide C-max and AUC (0–24h) values in EIAC pts, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy endpoint at the planned interim analysis with 5 of the first 22 patients (23%) being progression-free at 6 mo. RNA array analysis, performed in paired baseline and post-vorinostat treatment samples in a separate subgroup of 5 surgical recurrent GBM pts, who received vorinostat for 6 doses prior to surgery, showed upregulation of E-cadherin (p=0.02), thus indicating a biologic effect of the HDAC inhibitor on the glioblastoma tumors. Histone acetylation, Akt, phospho-Akt, P21
Waf1/Cip1
and P27
Kip1
expression analysis in all patients and correlation with outcome is ongoing. Conclusions: Vorinostat is well tolerated in recurrent GBM patients. EIAC patients have less toxicity, likely due to increased vorinostat metabolism via glucuronidation. Interim efficacy analysis is indicative of antitumor activity. Final efficacy analysis, RNA array data and correlative tissue analysis will be reported.
No significant financial relationships to disclose.
A large-scale trial of the effect of different commercial diets on the incidence of preclinical spinal deformation, as assessed by radiography, and the influence of two contrasting rearing systems ...was carried out. Two sets of three populations of Atlantic salmon, each of 20 000 first feeding fry of identical hatchery origin, created from equal numbers of eggs from 15 different families, were reared under commercial conditions on two different farms. Three commercial (closed formula) extruded fish meal-based diets were used in this study (diets A, B & C). Each diet was fed to one population of 20 000 fish at each site. Fish were fed a percentage of their body weight per day, with feeding rates set at commercial levels, based on water temperature, day length and fish biomass. Additional hand feeding was used to ensure satiation in all tanks. Fish in each tank were bulk-weighed and counted at the beginning and at 2-week intervals throughout the study. The fish were grown for 30 weeks. In addition, phosphorus (P) digestibility was evaluated by in-feed absorption testing in rainbow trout. The morphology of the radiographic lesions conformed to those described previously. Statistical analysis using multivariate regression analysis showed that date of sampling, site and diet were all statistically significant (P < 0.001) on univariable analysis. Farm A had significantly more affected fish than farm B (P < 0.001), which may have been attributable to variation in dissolved oxygen levels. The available dietary P levels were low in each diet. The number of fish affected in the group of fish being fed diet B was significantly lower than in the groups being fed diets A or C (P < 0.001). It appears most likely that the occurrence of preclinical radiographically apparent defects in parr which are believed to lead to the condition known as 'spinal deformity' is predominantly caused by a deficiency of available dietary P in first-feeding fry. The availability of dietary P may also vary considerably between diets formulated using different ingredients. Phytate-P associated with plant ingredients may affect the availability of P as well as other essential dietary nutrients. Additionally, diets for the production of salmonids in fresh water are currently formulated to keep P effluent to a minimum compatible with healthy spinal development. These various factors combine to make it crucial that small Atlantic salmon, especially first-feeding fry, are provided with carefully formulated diets fortified to an adequate level with a high quality source of available P.
Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ...ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0·026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range SIR) circulating six-hour post-pill total T4 (53·6 27·9 nmol/litre) and cTSH (0·03 0 μg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29·3 (12·7) nmol/litre and 0·15 (0·62) μg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.
Objectives: To examine older persons' willingness to participate in exercise and relaxation programs for managing chronic pain, to identify characteristics associated with willingness to participate, ...and to ascertain their barriers to participation.
Design: Cross‐sectional survey.
Setting:
A geriatric ambulatory care practice located in New York, New York, and the General Clinical Research Center of Weill Cornell Medical College.
Participants: Sixty‐eight English‐speaking patients aged 70 and older with chronic pain.
Measurements: Participants' level of willingness to participate in the programs was assessed using 5‐point Likert scales, and information regarding their demographic, clinical, psychological, and pain status was obtained. Qualitative methods were used to ascertain participants' perceived barriers to participation.
Results: Participants had a mean age±standard deviation of 81.9±7.0 and were mostly white (85%) and female (68%). Although only 16% of participants reported current use of exercise as a pain‐management strategy, 73% reported a willingness to try the exercise program. Four percent reported current use of relaxation methods; 70% reported an interest in learning these techniques. Moderate correlations were found between increasing days of restricted activity due to pain and greater willingness to participate. Seventeen unique barriers were identified; the mean number of barriers reported per person was 2.9±1.8 for exercise and 2.2±1.4 for relaxation. Commonly reported barriers to participating in either program included time conflicts, transportation, treatment efficacy concerns, and fear of pain or injury.
Conclusion: Older primary care patients with chronic pain are willing to try exercise and relaxation therapies to help manage pain but report a substantial number of barriers to participating in these programs. Addressing patient‐level barriers could improve engagement in and adherence to exercise and relaxation therapies for managing pain in older persons.
Electrical measurements on shallow Si n/sup +/-p junction diodes with a 30-nm TiSi/sub 2/ contacting layer demonstrate that an 80-nm-thick amorphous Ta/sub 36/Si/sub 14/N/sub 50/ film prepared by ...reactive RF sputtering of a Ta/sub 5/Si/sub 3/ target in an Ar N/sub 2/ plasma very effectively prevents the interaction between the Si substrate with the TiSi/sub 2/ contacting layer and a 500-nm Cu overlayer. The Ta/sub 36/Si/sub 14/N/sub 50/ diffusion barrier maintains the integrity of the I-V characteristics up to 900 C for 30-min annealing in vacuum. It is concluded that the amorphous Ta/sub 36/Si/sub 14/N/sub 50/ alloy is not only a material with a very low reactivity for copper, titanium, and silicon, but must have a small diffusivity for copper as well.< >
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