Differences in skin carcinogenesis by methylnitrosourea between mice of several strains.
To compare the susceptibilities of the skin of different strains of mice to the carcinogenic effect of a directly acting alkylating agent, groups of 20 mice were treated twice a week with 25 microliters of a solution of methylnitrosourea in methanol. The solution was 0.04M and was applied to the shaved back of female BALB/c, Sencar, CD-1 and Swiss mice for 25 weeks. Four groups of 20 mice of each strain were 8 weeks old at the beginning of treatment. Another four groups were 58 weeks old when treatment began. More of the BALB/c mice developed skin tumors than the other three strains, the Sencar mice somewhat less. Few CD-1 mice developed skin tumors and about one third of the Swiss mice. In all four strains, there were fewer animals with skin tumors among those begun at 58 weeks than in the young mice, but the difference was small. Survival was poor among CD-1 mice, but there was not a large difference between the strains in time of appearance of first tumor, or in average latent period of skin tumors, almost all of which were carcinomas. The Sencar mice were not outstandingly more sensitive to skin carcinogenesis by MNU, as they were to UV radiation-induced skin carcinogenesis. In a comparable study in Swiss mice neither dimethylnitrosourea nor diethylnitrosourea induced skin tumors by painting and both showed only a weak systemic carcinogenic effect in the lungs, although they are directly acting mutagens.


Imaging of cancer predisposition syndromes.
Pediatric cancer predisposition syndromes comprise a group of diseases characterized by specific tumors or a concomitance of tumors in infants, children and adolescents, suggesting a genetic cancer susceptibility condition. Most but not all have germline pathogenic variants on genetic testing. For some children with cancer predisposition syndromes, this diagnosis is based on their own or a family history of related neoplasms, or associated clinical manifestations. These tumors have variable incidence and age of onset. Imaging encompasses investigation in symptomatic children for diagnosis, staging and monitoring for treatment response and metastatic disease, as well as surveillance for primary tumors in asymptomatic children. In this review the author focuses on the role of surveillance imaging in childhood cancer predisposition syndromes, whole-body magnetic resonance imaging (whole-body MRI) in particular. Diagnosis and staging of specific tumors are addressed elsewhere in this series. The benefits of surveillance imaging include early detection and improved outcomes and are still being established for a number of cancer predisposition syndromes. The benefits must be weighed against risks including potential technique-related issues relating to sedation or contrast agents, false-positive imaging findings, and cost - both financial and psychosocial. The author discusses general principles for whole-body MRI interpretation along with findings in specific syndromes where whole-body MRI screening is recommended, such as Li-Fraumeni syndrome.


Pulse pressure as a prognostic marker in patients receiving extracorporeal life support.
It is not easy to predict the prognosis of patients receiving extracorporeal life support (ECLS) because of the highly variable situation around its implementation. We evaluated the role of pulse pressure (PP), which is available on real-time basis, as a hemodynamic prognostic marker during ECLS. From January 2009 to August 2011, data from 69 patients who were treated with ECLS for at least 6h in a single center for any cause was collected. We calculated the mean PP over the first 6h after ECLS implantation and examined if there was any correlation between mean PP and the study endpoints, in-hospital death and ECLS weaning failure. The causes of ECLS were of cardiac origin in 36 patients (52%). 27 patients (39.1%) weaned off ELCS and 13 patients (18.8%) survived to discharge. In Cox regression analysis (with age, Killip class ≥3, ECLS implementation during cardiopulmonary resuscitation (CPR), CPR duration, out-of-hospital arrest, initial laboratory results including blood gas analysis, initial systolic blood pressure (SBP), mean SBP over the first 6h after ECLS implantation, mean PP over the first 6h after ECLS implantation as independent variables), mean PP over the first 6h after ECLS implantation (hazard ratio [95% confidence interval]=0.96[0.94-0.98], P<0.001) and out-of-hospital arrest (HR[95%CI]=2.04[1.14-3.62], P=0.02) were independent predictors of in-hospital mortality and mean PP over the first 6h after ECLS implantation (HR[95% CI]=0.95[0.93-0.98], P<0.001) was the sole independent predictor of weaning failure. Higher mean PP over the initial 6h after ECLS implementation independently predicted successful weaning and survival. Our findings may help better predict and analyze prognosis in patients receiving ECLS.


19F NMR of trifluoroacetyl-labeled cysteine mutants of myoglobin: structural probes of nitric oxide bound to the H93G cavity mutant.
Nitric oxide (NO) binds to the myoglobin (Mb) cavity mutant, H93G, forming either a 5- or 6-coordinate Fe--NO heme complex. The H93G mutation replaces the proximal histidine of Mb with glycine, allowing exogenous ligands to occupy the proximal binding site. In the absence of the covalently attached proximal ligand, NO could bind to H93G from the proximal side of the heme rather than the typical diatomic binding pocket on the distal side when the 5-coordinate complex forms. The question of whether NO binds on the distal or proximal side was addressed by (19)F NMR. Site-directed mutagenesis was used to introduce unique cysteine residues at the protein surface on either the distal (S58C) or proximal (L149C) side, approximately equidistant from and perpendicular to the heme plane of both wild-type and H93G Mb. The cysteine thiols were alkylated with 3-bromo-1,1,1-trifluoroacetone to attach a trifluoroacetyl group at the mutation site. (19)F NMR spectra of 5-coordinate, NO bound S58C/H93G and L149C/H93G double mutants depict peaks with line widths of 100 and 23 Hz, respectively. As fluorine peaks broaden with increasing proximity to paramagnetic centers, such as 5-coordinate Fe--NO, the (19)F NMR data are consistent with NO binding in the distal heme pocket of H93G, even in the absence of a sixth axial ligand. Additionally, (19)F NMR spectra are reported for deoxy, oxy, CO, met CN, and met H(2)O forms of the labeled cysteine mutants. These results demonstrate that the fluorine probes are sensitive to subtle conformational changes in the protein structure due to ligation and oxidation state changes of the heme iron in Mb.


Drug sensitivity of Salmonella paratyphi A isolated from a suspected outbreak of enteric fever in Duliajan.
An outbreak of paratyphoid fever due to Salmonella paratyphi A occurred during June 1991 to March 1992 in Duliajan, Assam. S paratyphi A was isolated from blood, stool, urine and gall bladder content. Most of the strains (92%) were resistant to ampicillin and a few (10%) to chloramphenicol. Most of the strains belonged to phage type I.


[Statins: hepatotoxicity and monitoring].
Statins are among the most widely prescribed drugs throughout the industrialized world. Their benefits in primary and secondary prevention of cardiovascular events are undeniable. An asymptomatic increase in aminotransferase levels, generally less than 3 times the upper limit of normal range, is often observed in patients receiving statins. It is dose-dependent and often regresses even though treatment continues. A significant increase in aminotransferase levels is very rare in patients receiving statins Cases of hepatocellular, cholestatic, and mixed pattern liver injuries have been described, but severe hepatitis is rare. Cases mimicking autoimmune hepatitis have been described. There is usually no cross hepatotoxicity between the different statins. When indicated, statins may be used in patients with nonalcoholic fatty liver, chronic viral hepatitis or compensated cirrhosis. Statins should not be used in patients with decompensated cirrhosis.


Bilateral elastofibroma dorsi: proper positioning for an accurate diagnosis.
Elastofibroma dorsi is a rare, slow-growing, ill-defined soft tissue tumor of the chest wall, most commonly located beneath the rhomboid major and latissimus dorsi muscles. It is usually unilateral, and bilateral involvement occurs in only 10% of patients. We report herein a case of a 56-year-old woman with bilateral elastofibroma dorsi. The patient was found to have bilateral involvement of the tumor following a physical examination with proper positioning. An elastofibroma should be considered in the differential diagnosis of tumors deeply located at the periscapular area. Meticulous physical examination may reveal a nonpalpable coexisting tumor with deep subscapular location and help the accurate diagnosis of bilateral elastofibroma dorsi, hence preventing a secondary operation.


D-Lactate metabolism and the obligate requirement for CO2 during growth on nitrite by the facultative lithoautotroph Nitrobacter hamburgensis.
Nitrobacter hamburgensis X14 is a facultative lithoautotroph that conserves energy from the oxidation of nitrite (NO(-)2) and fixes carbon dioxide (CO(2)) as its sole source of carbon. The availability of the N. hamburgensis X14 genome sequence initiated a re-examination of its mixotrophic and organotrophic potential, as genes encoding three flavin-dependent oxidases were identified that may function to oxidize lactate, providing energy and carbon for growth. The response of N. hamburgensis to D- and L-lactate in the presence (mixotrophy) and absence (organotrophy) of NO(-)2 was examined. L-lactate did not support organotrophic growth or stimulate mixotrophic growth. In contrast, D-lactate enhanced the growth rate and yield of N. hamburgensis in the presence of NO(-)2, and served as the sole carbon and energy source for growth in the absence of NO(-)2 with ammonium as the sole nitrogen source. Lithoautotrophically grown cells immediately consumed D-lactate, suggesting that a lactate metabolic pathway is constitutively expressed. Nevertheless, a physiological adaptation to lactate occurred, as D-lactate-grown cells consumed and assimilated lactate at a faster rate than NO(-)2-grown cells, and the D-lactate-dependent O(2) uptake rate was significantly greater in cells grown either organotrophically or mixotrophically compared with cells grown lithoautotrophically. Although D-lactate was assimilated and metabolized to CO(2) in the presence or absence of NO(-)2, exposure to atmospheric CO(2) or the addition of 0.75 mM sodium carbonate was required for mixotrophic growth and for optimum organotrophic growth on D-lactate.


T1 mapping for detection of left ventricular myocardial fibrosis in hypertrophic cardiomyopathy: a preliminary study.
To investigate the diagnostic value of T1 mapping imaging of evaluating fibrosis in patients with hypertrophic cardiomyopathy (HCM). 21 subjects with HCM and 18 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 mapping imaging. The region of myocardium in HCM is divided into remote area of LGE, peri-LGE, LGE (halo-like LGE and typical patchy LGE). These regions combined with normal volunteers' myocardium were calculated by the reduced percent of T1 value (RPTV). The RPTV in healthy volunteers was no significant comparing with that in the remote area of LGE in HCM subjects (3.98 ± 3.19 vs. 3.34 ± 2.75, P>0.05). There were significant statistical differences in pairwise among the remote area of LGE, peri-LGE, halo-like LGE and typical patchy LGE in the RPTV (P<0.0001). ROC curves indicated that the T1 mapping imaging has a greater area under the curve comparing with that of traditional LGE imaging (0.975 ± 0.07 vs. 0.753 ± 0.26, P<0.0001). HCM has a high prevalence of fibrosis and with varying severity. T1 mapping imaging can be a useful method to evaluate the severity of the fibrosis in HCM.


[A case of adult onset Still's disease complicated with adult respiratory distress syndrome and disseminated intravascular coagulation].
A 71 year-old man with adult onset Still's disease was admitted to our hospital because of fever, sore throat, myalgia and macular nonpruritic salmon pink eruption. He was treated with prednisolone, 40 mg daily and these symptoms disappeared. When the dose of prednisolone was reduced to 30 mg daily, he began to notice fever. 5 days later he developed adult respiratory distress syndrome (ARDS). The dose of prednisolone was increased to 50 mg daily and oxygen administration was started. All symptoms began to improve immediately and the dose of prednisolone was decreased to 40 mg daily. 10 days later he noticed fever and skin rash. Laboratory investigation showed platelet counts of 69,000/mm3, a ferritin of 37,000 ng/ml, and increased fibrinogen degradation product, indicating increased activity of adult onset Still's disease associated with disseminated intravascular coagulation (DIC). The dose of prednisolone was again increased to 60 mg daily, and 100 mg of nafamostat mesilate was administrated intravenously. All above symptoms associated with adult onset Still's disease and DIC disappeared. The dose of prednisolone was gradually decreased and the clinical course was uneventful with daily administration of 10 mg of prednisolone. Although there are a couple of case report which described the association of adult onset Still's disease with either ARDS or DIC, the association of adult onset Still's disease with both ARDS and DIC have not been reported yet.


Foetal craniopharyngioma diagnosed by prenatal ultrasonography and confirmed by histopathological examination.
Craniopharyngioma is an intracranial tumour, which usually develops in children and young adults and rarely occurs in intrauterine life. In foetal life, ultrasonography and later computed tomography (CT) and magnetic resonance imaging (MRI) are regarded to be the most effective tools of diagnosis. In the seven cases published earlier, tumour size was below our finding of 96 x 80 x 65 mm(3). In relation to the current case report, we aimed at surveying the available information on prenatal craniopharyngioma. Although the tumour is benign, the neurological and ophthalmologic complications, arising due to its expansive growth, are suggestive of a poor prognosis. Despite the high mortality and morbidity rates, neurosurgical treatment appears to be the sole option.


Enhancement of stochastic resonance in distributed systems due to a selective coupling
Recent massive numerical simulations have shown that the response of a "stochastic resonator" is enhanced as a consequence of spatial coupling. Similar results have been analytically obtained in a reaction-diffusion model, using nonequilibrium potential techniques. We now consider a field-dependent diffusivity and show that the selectivity of the coupling is more efficient for achieving stochastic-resonance enhancement than its overall value in the constant-diffusivity case.


Midkine and pleiotrophin in neural development and cancer.
The midkine (MK) family consists of only two members, namely heparin-binding growth factors MK and pleiotrophin (PTN). During embryogenesis, MK is highly expressed in the mid-gestational period, whereas PTN expression reaches the maximum level around birth. Both proteins are localized in the radial glial processes of the embryonic brain, along which neural stem cells migrate and differentiate. Zebrafish and Xenopus MK can induce neural tissues. In addition, deposits of MK and/or PTN are found in neurodegenerative diseases, such as Alzheimer's disease and multiple system atrophy. Both molecules are induced in reactive astrocytes by ischemic insults. In this context, it is interesting that LDL receptor-related protein is a receptor for MK and PTN, and this receptor has been implicated in the pathogenesis of Alzheimer's disease. MK and PTN share receptors, and show similar biological activities that include fibrinolytic, anti-apoptotic, mitogenic, transforming, angiogenic, and chemotactic ones. These activities explain how these molecules are involved in carcinogenesis. MK is detected in human carcinoma specimens from pre-cancerous stages to advanced stages. Strong expression of PTN is also detected in several carcinomas, although, in general, MK is expressed more intensely and in a wide range of carcinomas than PTN. The blood MK level is frequently elevated in advanced human carcinomas, decreases after surgical removal of the tumors, and is correlated with prognostic factors. Thus, it is a good market for evaluating the progress of carcinomas. Furthermore, antisense oligonucleotides for MK and ribozymes for PTN show anti-tumor activity. Therefore, MK and PTN are candidate molecular targets for therapy for human carcinomas.


An occupational therapy Internet school.
Four centres in the UK, Belgium, the Netherlands and Sweden have collaborated to provide Internet-based courses for student and professional occupational therapists. The basis of the occupational Therapy Internet School (OTIS) is the concept of the 'virtual college'. This comprises the design and implementation of a sophisticated Internet-based system through which courses can be managed, prepared and delivered on line, and through which students can communicate both with the staff and their peers. The aim is to support and facilitate the whole range of educational activities within a remote electronic environment.


Open reduction of nasal fractures.
Open reduction of nasal fractures has been defined and discussed from a clinical standpoint. Specific advantages of the procedure are mentioned with the suggestion that perhaps more of these procedures should be performed. Reference is made to the authors' series of 788 cases, with analysis of type of injury, age group, and procedure performed.


Thermoactive β-N-acetylhexosaminidase production by a soil isolate of Penicillium monoverticillium CFR 2 under solid state fermentation: parameter optimization and application for N-acetyl chitooligosaccharides preparation from chitin.
Two fungal strains were evaluated for β-N-acetylhexosaminidase production by solid state fermentation using different agro-industrial residues such as commercial wheat bran (CWB) and shrimp shell chitin waste (SSCW), of which Penicillium monoverticillium CFR 2 a local soil isolate showed significantly (P ≤ 0.001) higher β-N-acetylhexosaminidase activity on CWB medium as compared with the activity of Fusarium oxysporum CFR 8. Fermentation parameters such as incubation temperature, incubation time, initial moisture content and inoculum concentration were optimized by statistically designed experiments, using 3**(4-1) fractional factorial design of Response Surface Methodology. The high R(2) (0.9512) observed during validation experiment showed the usefulness of the model. Highest level of enzyme activity (311.84 U/g IDS) was predicted at 75% (w/w) initial moisture content, 26 °C incubation temperature, 168 h incubation time and initial inoculum, at the highest concentration tested (2.95 ml spore suspension/5 g substrate). Statistical optimization yielded a 4.5 fold increase in β-N-acetylhexosaminidase activity. The crude β-N-acetylhexosaminidase showed optimum temperature of 57 ± 1 °C and pH of 3.6 and retained 50% activity after 1 h of incubation at 57 ± 1 °C. SDS-PAGE zymogram revealed crude enzyme was a monomer with an apparent molecular weight ~110 kDa. The crude enzyme formed 6.81 ± 0.03 mM/l of N-acetyl chitooligosaccharides from colloidal chitin in 24 h of incubation. HPLC analysis revealed hydrolysate contained 37.57% N-acetyl chitotriose and 62.43% N-acetyl chitohexose, indicating its potential for specific N-acetyl chitooligosaccharides production.


The glp-1 locus and cellular interactions in early C. elegans embryos.
Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans.


[Effect of parenterally administered protein hydrolysates on the motor function of the stomach and small intestine].
Intravenous administration of proteinic hydrolysates (caseine and aminopeptide hydrolysates) to dogs for a duration of 2 hours debars on active period in the fasting periodic activity of the stomach, this being attended by the stimulation of gastric secretion with pH changing from alkaline or neutral to acid reaction. Introduction of the caseine and aminopeptide hydrolysate did not cancell out the active period of the duodenal motoricity, though the frequency of contractions was somewhat below that in controls.


[Anterior decompression and spinal stabilization in the treatment of dorsolumbar metastatic compression].
The authors report their experience of the postero-lateral approach for the treatment of thoraco-lumbar spinal metastasis with anterior decompression and osteosynthesis. They stress the progress in the surgical technique which is designed to have a direct effect on osseous posterior wall compression with a more effective osteosynthesis to allow an immediate mobilization.


A systematic review of perinatal depression interventions for adolescent mothers.
Poor, adolescent, racial/ethnic minority women are at great risk for developing perinatal depression. However, little research has been conducted evaluating interventions for this population. We conducted a systematic review of preventive and treatment interventions for perinatal depression tested with adolescents, with a focus on low income, minority populations. Nine research-based articles (including one that reported on two studies) were reviewed systematically, and quality ratings were assigned based on a validated measure assessing randomization, double-blinding, and reporting of participant withdrawals. Two treatment studies were identified, both of which were successful in reducing depression. Eight prevention studies were located, of which four were more efficacious than control conditions in preventing depression. Studies sampled mostly minority, low socioeconomic status adolescents. No consistent characteristics across efficacious interventions could be identified. This review underscores the need for researchers to further investigate and build an evidence base.


The effect of carbachol and isoprenaline on cell division in the exocrine pancreas of the rat.
The effect of muscarinic cholinergic receptor stimulation on pancreatic acinar cell division has been investigated. Muscarinic receptor stimulation, in addition to causing a 50% depletion of amylase in the pancreas after 4 h, resulted in a 400% increase in the incorporation of [6(-3)H]thymidine 27 h after drug administration. This increase in incorporation was dose-dependent. Autoradiography showed this increase to be due to an increased acinar cell labelling. Isoprenaline also increased the incorporation of [6(-3)H]thymidine into the pancreas but did not reduce enzyme levels. However, with isoprenaline there was no increase in acinar cell labelling. The possibility of a relationship between secretion and hyperplasia of acinar cells in the rat pancreas is discussed.


[Primary lymphoma of the central nervous system. Apropos of 8 cases].
Eight cases of intracranial primary lymphoma are reported. This condition accounts for 1.6% of all lymphomas. Although diagnosis is only confirmed by cerebral biopsy or surgical excision, it may be suggested by CT scan in multifocal forms. No localizations were demonstrated outside the CNS upon thorough clinical and radiological investigations or postmortem examination. Prognosis is poor: 5 patients died within four months. Tumor size and meningeal invasion are of more prognostic significance than the histological type. The authors advocate conventional radiotherapy delivering 45 000 grays over 5 weeks. Chemotherapy must be added in huge tumors or when meningeal invasion is present.


Synthetic procedure for N-Fmoc amino acyl-N-sulfanylethylaniline linker as crypto-peptide thioester precursor with application to native chemical ligation.
N-sulfanylethylanilide (SEAlide) peptides 1, obtainable using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS), function as crypto-thioesters in native chemical ligation (NCL), yielding a wide variety of peptides/proteins. Their acylating potential with N-terminal cysteinyl peptides 2 can be tuned by the presence or absence of phosphate salts, leading to one-pot/multifragment ligation, operating under kinetically controlled conditions. SEAlide peptides have already been shown to be promising for use in protein synthesis; however, a widely applicable method for the synthesis of N-Fmoc amino acyl-N-sulfanylethylaniline linkers 4, required for the preparation of SEAlide peptides, is unavailable. The present study addresses the development of efficient condensation protocols of 20 naturally occurring amino acid derivatives to the N-sulfanylethylaniline linker 5. N-Fmoc amino acyl aniline linkers 4 of practical use in NCL chemistry, except in the case of the proline- or aspartic acid-containing linker, were successfully synthesized by coupling of POCl(3)- or SOCl(2)-activated Fmoc amino acid derivatives with sodium anilide species 6, without accompanying racemization and loss of side-chain protection. Furthermore, SEAlide peptides 7 possessing various C-terminal amino acids (Gly, His, Phe, Ala, Asn, Ser, Glu, and Val) were shown to be of practical use in NCL chemistry.


Effects of a modified ambulance night shift system on fatigue and physiological function among ambulance paramedics.
In the present study, we modified a night shift system for an ambulance service so that ambulance paramedics were assured of taking a nap, and examined the effects of this new system on the fatigue and physiological function of ambulance paramedics. Ten ambulance paramedics at a fire station in the center of a large city in Japan voluntarily enrolled as subjects in this field study. They worked a 24-h shift system. There were two teams of 5 ambulance paramedics in the fire station. Three ambulance paramedics per shift usually provided the emergency services. In the traditional system, the ambulance paramedics had to deal with all emergency calls throughout a 24-h shift (T-shift). In the modified system, 2 ambulance paramedics were allotted time for naps in the 21:00-3:00 (C-shift) or 3:00-8:30 (B-shift) shift by the addition of another a firefighter (D-shift). There were fewer emergency dispatches and nap time was longer in the B- and C-shifts than in the T-shift. Parasympathetic nerve activities during naps in B- and C-shifts were higher than in the T-shift. The results of critical flicker fusion frequency and 3-choice reaction time in the B-shift at 7:30 tended to be higher and shorter than that in T-shift. The results of this study suggest that the modified night shift which ensured time for ambulance paramedics to take long, restful power naps alleviated subjective fatigue, and improved physiological functions which are often adversely affected by night workload.


Impact of substance disorders on medical expenditures for medicaid beneficiaries with behavioral health disorders.
This study measured the impact of substance use disorders on Medicaid expenditures for behavioral and physical health care among beneficiaries with behavioral health disorders. Claims for Medicaid beneficiaries with behavioral health diagnoses in 1999 from Arkansas, Colorado, Georgia, Indiana, New Jersey, and Washington were analyzed. Behavioral health and general medical expenditures for individuals with diagnoses of substance use disorders were compared with expenditures for those without such diagnoses. States were analyzed separately with adjustment for confounders. A total of 148,457 beneficiaries met selection criteria, and 43,457 (29.3%) had a substance use diagnosis. Compared with other beneficiaries with behavioral health disorders, individuals with diagnoses of substance use disorders had significantly higher expenditures for physical health problems in five of six states. Approximately half of the additional care and expenditures were for treatment of physical conditions. Differences declined but remained statistically significant after adjustment for higher overall disease burden among beneficiaries with addictions. Medical expenditures for individuals with diagnoses of substance use disorders increased significantly with age in five of six states, whereas behavioral health expenditures were stable or declined. Hospital admissions for psychiatric and general medical reasons were higher for those with diagnoses of substance use disorders. The impact of addiction on Medicaid populations with behavioral health disorders is greater than the direct cost of mental health and addictions treatment. Higher medical expenditures can be partly attributed to greater prevalence of co-occurring physical disorders, but expenditures remained higher after adjustment for disease burden. Spending estimates based only on behavioral health diagnoses may significantly underestimate addictions-related costs, particularly for older adults.


The rapid detection of methyl tert-butyl ether (MtBE) in water using a prototype gas sensor system.
The gasoline additive Methyl-tertiary-Butyl Ether (MtBE) is the second most common contaminant of groundwater in the USA and represents an important soil contaminant. This compound has been detected in the groundwater in at least 27 states as a result of leaking underground storage facilities (gasoline storage tanks and pipelines). Since the health effects of MtBE are unclear the potential threat to drinking water supplies is serious. Therefore, the ability to detect MtBE at low levels (ppb) and on-line at high-risk groundwater sites would be highly desirable. This paper reports the use of 'commercial' and metal oxide sensor arrays for the detection of MtBE in drinking and surface waters at low ppb level (microg.L(-1) range). The output responses from some of the sensors were found to correlate well with MtBE concentrations under laboratory conditions.


Utilization of mouse models in the discovery of human disease genes.
The mouse is a powerful model organism for studying human disease. By the use of various breeding strategies in combination with positional cloning and positional candidates, many genes underlying human disease have been and will continue to be discovered through the use of mouse genetics. The author illustrates how the mouse can be used to discover human disease genes underlying simple mendelian and complex polygenic diseases and genes involved in the modification of disease.


[Adductor muscle pyomyositis simulating acute appendicitis: CT and MR imaging findings].
Pyomyositis is a primary bacterial infection of skeletal muscle. This infection tends to occur in the large muscles of the lower extremity. Pyomyositis of the proximal muscles of the thigh can simulate acute abdominal disease. Early diagnosis improves the outcome. Delayed diagnosis may lead to septicemia and shock. We report the CT and MRI findings in a patient with pyomyositis of the proximal muscles of the thigh.


Social stressors, social supports, and self-esteem as predictors of morbidity in adults with chronic lung disease.
Psychosocial correlates of morbidity and functional status were examined in 44 white adults with chronic lung disease. Demographic characteristics, functional status, stressful life changes, social supports, and self-esteem were assessed at baseline by a self-administered questionnaire. Hospital days, bed-disability days, restricted-activity days, and physician visits were then measured prospectively by mailed questionnaire over the next 6 months. There were no cross-sectional associations of psychosocial variables with demographic characteristics. Better functional status (measured by the Sickness Impact Profile) was associated with a lower 12-month life-change score (measured by the Social Readjustment Rating Scale), with stronger social supports (measured by a 13-item index), and with higher self-esteem (measured by the Rosenberg Scale). On bivariate analysis, higher life-change score predicted higher levels of all four morbidity variables; low social supports predicted increased bed days, restricted-activity days, and physician visits; and low self-esteem predicted high restricted-activity. After controlling for demographic characteristics and baseline function by multivariate analysis, low social supports continued to predict higher rates of physician visits, but the other associations of psychosocial variables with morbidity were no longer statistically significant. The results suggest that patients with weak social supports have increased use of physician services.


Intraoperative behavior of arterial grafts in the elderly and the young: a flowmetric systematic analysis.
Extensive arterial grafting (Art-CABG) in the elderly is still questioned due to the reduced life expectancy and the supposed higher periprocedural risk. Reports further demonstrated accelerated atherosclerosis of arterial grafts in the elderly, with hampered short-term and long-term results. We reviewed our experience of patients undergoing Art-CABG between January 2003 and January 2007, divided into two groups: the elderly (238 patients > or = 70 years; Group A) and the young (195 patients < or = 60 years; Group B). Transit time flowmetric (TTF) maximum and mean flow, pulsatility index (PI), and graft flow reserve (GFR) were compared. Hospital outcome was analyzed. Hospital mortality, need for intra-aortic balloon pump, troponin I, and echocardiographic segmental kinetics were comparable between the two groups (P = not significant [NS]). Stratifying patients for target vessels and type of arterial CABG, no differences in TTF results were recorded between the two groups either on-pump (P = NS) and off-pump (P = NS), both for the two internal mammary arteries (P = NS irrespective of the target vessel) and the radial artery conduits (P = NS irrespective of the target vessel). Although graft flow reserve was significantly recruited in all patients (P < 0.05 in young and elderly, either on-pump and off-pump, irrespective of the arterial conduit and the grafted vessel), GFR of all arterial grafts was comparable between elderly and young patients, either on-pump (P = NS) or off-pump (P = NS). Art-CABG showed similar TTF results in elderly and young patients, regardless of the arterial conduit, target vessel, or surgical technique employed. These functional results supported the reported survival benefit of arterial revascularization in the elderly.


Effects of diversity and procrastination in priority queuing theory: the different power law regimes.
Empirical analyses show that after the update of a browser, or the publication of the vulnerability of a software, or the discovery of a cyber worm, the fraction of computers still using the older browser or software version, or not yet patched, or exhibiting worm activity decays as a power law approximately 1/t(alpha) with 0<alpha<or=1 over a time scale of years. We present a simple model for this persistence phenomenon, framed within the standard priority queuing theory, of a target task which has the lowest priority compared to all other tasks that flow on the computer of an individual. We identify a "time deficit" control parameter beta and a bifurcation to a regime where there is a nonzero probability for the target task to never be completed. The distribution of waiting time T until the completion of the target task has the power law tail approximately 1/t(1/2), resulting from a first-passage solution of an equivalent Wiener process. Taking into account a diversity of time deficit parameters in a population of individuals, the power law tail is changed into 1/t(alpha), with alpha is an element of (0.5,infinity), including the well-known case 1/t. We also study the effect of "procrastination," defined as the situation in which the target task may be postponed or delayed even after the individual has solved all other pending tasks. This regime provides an explanation for even slower apparent decay and longer persistence.


Effects of Oral Chondroitin Sulfate on Osteoarthritis-Related Pain and Joint Structural Changes: Systematic Review and Meta-Analysis.
Osteoarthritis (OA) is a disorder involving the deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. In military personnel, the incidence of OA has increased between 2000 and 2012 and was the first or second leading cause of medical separations in this period. It has been suggested that consumption of chondroitin sulfate (CS) may reduce the pain and joint deterioration associated with OA. This article reports on a systematic review and meta-analysis of the effectiveness of CS on reducing OA-related pain and joint deterioration. PubMed and Ovid Embase databases and other sources were searched to find randomized, double-blind, placebo-controlled trials on the effects of orally consumed CS on pain and/or joint structure. The outcome measure was the standardized mean difference (SMD) which was the improvement in the placebo groups minus the improvement in the CS groups divided by the pooled standard deviation. There were 18 trials meeting the review criteria for pain with SMD -0.41, 95% confidence interval (95% CI) -0.57 to -0.25 (negative SMD favors CS). Six studies met the review criteria for joint space narrowing with SMD -0.30, 95% CI -0.61 to +0.00. Two studies meet the review criteria for cartilage volume with SMD -0.11, 95% CI -0.48 to +0.26. Larger dosages (1200mg/d) had greater pain reduction efficacy than lower dosages (≤ 1000mg/d). These data suggest that CS has small to moderate effectiveness in reducing OA-related pain but minimal effects on joint space narrowing and no effect on cartilage volume. It is important that clinicians recommend pharmaceutical-grade CS to their patients due to the variability in the amount of CS in dietary supplements purporting to contain CS.


Intracranial arterial wall imaging using three-dimensional high isotropic resolution black blood MRI at 3.0 Tesla.
To develop a high isotropic-resolution sequence to evaluate intracranial vessels at 3.0 Tesla (T). Thirteen healthy volunteers and 4 patients with intracranial stenosis were imaged at 3.0T using 0.5-mm isotropic-resolution three-dimensional (3D) Volumetric ISotropic TSE Acquisition (VISTA; TSE, turbo spin echo), with conventional 2D-TSE for comparison. VISTA was repeated for 6 volunteers and 4 patients at 0.4-mm isotropic-resolution to explore the trade-off between SNR and voxel volume. Wall signal-to-noise-ratio (SNR(wall) ), wall-lumen contrast-to-noise-ratio (CNR(wall-lumen) ), lumen area (LA), wall area (WA), mean wall thickness (MWT), and maximum wall thickness (maxWT) were compared between 3D-VISTA and 2D-TSE sequences, as well as 3D images acquired at both resolutions. Reliability was assessed by intraclass correlations (ICC). Compared with 2D-TSE measurements, 3D-VISTA provided 58% and 74% improvement in SNR(wall) and CNR(wall-lumen) , respectively. LA, WA, MWT and maxWT from 3D and 2D techniques highly correlated (ICCs of 0.96, 0.95, 0.96, and 0.91, respectively). CNR(wall-lumen) using 0.4-mm resolution VISTA decreased by 27%, compared with 0.5-mm VISTA but with reduced partial-volume-based overestimation of wall thickness. Reliability for 3D measurements was good to excellent. The 3D-VISTA provides SNR-efficient, highly reliable measurements of intracranial vessels at high isotropic-resolution, enabling broad coverage in a clinically acceptable time.


Removal of polybrominated diphenyl ethers by biomass carbon-supported nanoscale zerovalent iron particles: influencing factors, kinetics, and mechanism.
In this study, nanoscale zerovalent iron (NZVI) immobilized on biomass carbon was used for the high efficient removal of BDE 209. NZVI supported on biomass carbon minimized the aggregation of NZVI particles resulting in the increased reaction performance. The proposed removal mechanism included the adsorption of BDE 209 on the surface or interior of the biomass carbon NZVI (BC-NZVI) particles and the subsequent debromination of BDE 209 by NZVI while biomass carbon served as an electron shuttle. BC-NZVI particles and the interaction between BC-NZVI particles and BDE 209 were characterized by TEM, XRD, and XPS. The removal reaction followed a pseudo-first-order rate expression under different reaction conditions, and the k obs was higher than that of other NZVI-supported materials. The debromination of BDE 209 by BC-NZVI was a stepwise process from nona-BDE to DE. A proposed pathway suggested that supporting NZVI on biomass carbon has potential as a promising technique for in situ organic-contaminated groundwater remediation.


Contrast sensitivity and appearance in briefly presented illusory figures.
We examined the contributions of brightness enhancement, illusory figure formation and figural completion to changes in contrast sensitivity in contour gaps. The brightness on the border of a Kanizsa-square and an outline square was measured as the point of subjective equality with the background (PSE) for small line targets. Increment and decrement thresholds were measured at the same location. We found that contrast thresholds were lower than in a control condition without inducers, and that the threshold reduction was independent of the contrast polarity of the inducers. This reduction cannot be explained by a simple summation of stimulus contrast and induced brightness. In a second experiment the inducers that define the contour of the Kanizsa and the outline square were changed so that the figure was no longer closed, keeping the local stimulus surround constant. Thresholds were equally reduced for all conditions, independently of whether the figure was completed or not, or whether an illusory contour was perceived or not. The results suggest that the reduction of contrast threshold in contour gaps is independent of the brightness perceived in these gaps and of the formation of an illusory figure. Processes that cause contrast threshold reduction in contour gaps also seem to operate independently of figural completion.


Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism?
There are still controversies concerning the role of immunological mechanisms engaged both in recurrent abortions (RA) and pre-eclampsia (PE). According to some opinions, recurrent miscarriage is comparable to organ-specific autoimmune disease. Analysis of immune reactions shows that graft rejection shares many similar mechanisms with RA and PE. This fact allows us to conclude that rejection of transplanted alloantigenic organs and pregnancy loss have probably the same evolutionary origin. Subsets and functions of immunocompetent cells (T CD4, suppressor gammadeltaT, cytotoxic T CD8, Treg, Tr1, uterine NK cells), over-activation of innate immunity (activation of NK cytotoxic cells, macrophages, neutrophils and complement), changes of Th1/Th2 cytokine balance (IL-2, IL-12, IL-15, IL-18, IFNgamma, TNFalpha vs. IL-4, IL-10, TGFbeta), importance of HLA-G molecule, CD200/CD200R interaction, over-expression of adhesion molecules, fgl2 prothrombinase activation and stimulation of IDO and HO expression, all suggest that RA and PE are syndromes of fetal allograft rejection, and not organ-specific autoimmune diseases. According to that supposition, an analogy might exist between acute graft rejection and recurrent abortion, and between chronic graft rejection and pre-eclampsia.


Urethral plug--a new secondary male sex characteristic in rat and other rodents.
The plug is an eosinophilic mass, partly homogenous and partly porous, filling the proximal urethra in rats and occasionally extending into the bladder. Its average weight in 131 adult rats was 0.063 g. These plugs are normally present in the urethra of adult male rats, and this seems to be the case for all laboratory Muridae and Cavidae. The absence of a plug in an adult male may be a sign of abnormality associated with failing health. There is an interesting similarity between the amino acid composition of the content of seminal vesicles, that of the urethral plug, and that of the copulatory vaginal plug in female rodents.


Molecular modeling of freezing of simple fluids confined within carbon nanotubes.
We report Monte Carlo simulation results for freezing of Lennard-Jones carbon tetrachloride confined within model multiwalled carbon nanotubes of different diameters. The structure and thermodynamic stability of the confined phases, as well as the transition temperatures, were determined from parallel tempering grand canonical Monte Carlo simulations and free-energy calculations. The simulations show that the adsorbate forms concentric molecular layers that solidify into defective quasi-two-dimensional hexagonal crystals. Freezing in such concentric layers occurs via intermediate phases that show remnants of hexatic behavior, similar to the freezing mechanism observed for slit pores in previous works. The adsorbate molecules in the inner regions of the pore also exhibit changes in their properties upon reduction of temperature. The structural changes in the different regions of adsorbate occur at temperatures above or below the bulk freezing point, depending on pore diameter and distance of the adsorbate molecules from the pore wall. The simulations show evidence of a rich phase behavior in confinement; a number of phases, some of them inhomogeneous, were observed for the pore sizes considered. The multiple transition temperatures obtained from the simulations were found to be in good agreement with recent dielectric relaxation spectroscopy experiments for CCl(4) confined within multiwalled carbon nanotubes.


Intravenous immunoglobulin for prophylaxis of infection in preterm infants.
Immunodeficiency, particularly antibody deficiency, is a crucial contributory factor to the increased susceptibility to infections in preterm infants. Availability of the recent preparation of intravenous immunoglobulin (ivIgG) led several authors to evaluate the safety and effectiveness of ivIgG for prophylaxis of infection in preterm infants. The results of these studies, although controversial, have pointed out two common findings: (1) ivIgG prophylaxis seems to be effective only in the very preterm infants, with mean birth weight below about 1,300 g: (2) ivIgG seems to be well tolerated by newborn infants.


Tumor-Contacted Neutrophils Promote Metastasis by a CD90-TIMP-1 Juxtacrine-Paracrine Loop.
The different prognostic values of tumor-infiltrating neutrophils (TIN) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism.Experimental Design: We evaluated CD66b+ neutrophils in primary tumors from 341 patients with breast cancer from Sun Yat-sen Memorial Hospital by IHC. The association between stromal and parenchymal neutrophil counts and clinical outcomes was assessed in a training set (170 samples), validated in an internal validation set (171 samples), and further confirmed in an external validation set (105 samples). In addition, we isolated TINs from clinical samples and screened the cytokine profile by antibody microarray. The interaction between neutrophils and tumor cells was investigated in transwell and 3D Matrigel coculture systems. The therapeutic potential of indicated cytokines was evaluated in tumor-bearing immunocompetent mice. We observed that the neutrophils in tumor parenchyma, rather than those in stroma, were an independent poor prognostic factor in the training [HR = 5.00, 95% confidence interval (CI): 2.88-8.68, P < 0.001], internal validation (HR = 3.56, 95% CI: 2.07-6.14, P < 0.001), and external validation set (HR = 5.07, 95% CI: 2.27-11.33, P < 0.001). The mechanistic study revealed that neutrophils induced breast cancer epithelial-mesenchymal transition (EMT) via tissue inhibitor of matrix metalloprotease (TIMP-1). Reciprocally, breast cancer cells undergoing EMT enhanced neutrophils' TIMP-1 secretion by CD90 in a cell-contact manner. In vivo, TIMP-1 neutralization or CD90 blockade significantly reduced metastasis. More importantly, TIMP-1 and CD90 were positively correlated in breast cancer (r 2 = 0.6079; P < 0.001) and associated with poor prognosis of patients. Our findings unravel a location-dictated interaction between tumor cells and neutrophils and provide a rationale for new antimetastasis treatments.


The relation of early experienced negative life events and current itch. A longitudinal study among adolescents in Oslo, Norway.
Negative life events have impact on mental health and skin diseases among adults. Itch is a common, disabling skin symptom. The aim was to describe negative life events associated with current itch and to analyze the impact of number of negative life events on symptoms of itch, controlling for possible confounders. This school-based longitudinal survey was conducted among 15 and 18 years old high-school students in Oslo, Norway. From a baseline cohort of 3811 students, 2489 (65%) participants were followed-up after three years later. They completed questionnaires at baseline and follow-up. Current itch was measured with a validated instrument asking for symptoms on a four point Likert scale at follow-up. More girls than boys reported itch. There were no gender differences in number of negative life events. Death among close relative/friend was the most common negative life event among boys and girls. All negative life experiences before 15 years of age were statistically significantly associated with itch, but after 15 years only half of the negative life events were associated with itch. The bivariate association between number of negative life events and itch was statistically significant, and only when adjusting for mental distress at baseline there was a considerable drop in the Odds Ratio. There is a clear association between number of negative life events at baseline and itch at follow-up three years later among adolescents. It is therefore important to discuss possible adverse experiences with adolescents presenting with severe symptoms of itch.


Examination of hypochlorous acid-induced damage to cytosine residues in a CpG dinucleotide in DNA.
Inflammation-mediated, neutrophil-derived hypochlorous acid can damage DNA and result in the chlorination damage products 5-chlorocytosine and 5-chlorouracil as well as the oxidation damage products 5-hydroxycytosine and 5-hydroxyuracil. While 5-chlorocytosine could potentially perturb epigenetic signals if formed at a CpG dinucleotide, the remaining products are miscoding and could result in transition mutations. In this article, we have investigated the reaction of hypochlorous acid with an oligonucleotide site-specifically enriched with 15N to probe the reactivity of cytosine at CpG. These experiments demonstrate directly the formation of 5-chlorocytosine at a CpG dinucleotide in duplex DNA. We observe that chlorination relative to oxidation damage is greater at CpG by a factor of approximately two, whereas similar amounts of 5-chlorocytosine and 5-hydroxycytosine are formed at two non-CpG sites examined. The relative amounts of deamination of the cytosine to uracil derivatives are similar at CpG and non-CpG sites. Overall, we observe that the reactivity of cytosine at CpG and non-CpG sites toward hypochlorous acid induced damage is similar (5-chlorocytosine > 5-hydroxycytosine > 5-hydroxyuracil > 5-chlorouracil), with a greater proportion of chlorination damage at CpG sites. These results are in accord with the potential of inflammation-mediated DNA damage to both induce transition mutations and to perturb epigenetic signals.


Inhibition of growth of mammalian cell cultures by extracts of arginine-utilizing mycoplasmas.
Mechanisms of the inhibition of growth of mammalian cell cultures caused by mycoplasmal infection were investigated by using cell-free extracts of 14 species of mycoplasmas. In four mammalian cell lines tested, the growth of two cell lines, FM3A and MDCK, was inhibited by the extracts of arginine-utilizing mycoplasmas, whereas that of the other two cell lines, Vero and LLC-MK2, was not inhibited by extracts of either arginine- or glucose-utilizing mycoplasmas. These results suggest that there are two types of cell cultures, one susceptible and the other insusceptible to arginine-utilizing mycoplasmas. In a series of experiments using FM3A cells, it was found that the growth inhibition caused by the extracts of arginine-utilizing mycoplasmas was due to removal of arginine from the medium by the action of arginine deiminase present in the extracts and that none of the metabolic products of arginine had any effect on the growth. A highly positive correlation (r = 0.96, P less than 0.01) was observed between the activity of arginine deiminase and the growth-inhibiting activity of extracts of arginine-utilizing mycoplasmas.


Multiple types of spontaneous excitatory synaptic currents in salamander retinal ganglion cells.
Spontaneous and light-evoked excitatory postsynaptic currents (sEPSCs and leEPSCs) in retinal ganglion cells of the larval tiger salamander were recorded under voltage clamp conditions from living retinal slices. sEPSCs were isolated from the spontaneous inhibitory postsynaptic currents (sIPSCs) by application of 100 M picrotoxin+1 microM strychnine. In addition to the previously reported sEPSCs [K. Matsui, N. Hosoi, M. Tachibana, Excitatory synaptic transmission in the inner retina: pair recordings of bipolar cells and neurons of the ganglion cell layer, J. Neurosci. 18 (1998) 4500-4510; W.R. Taylor, E. Chen, D.R. Copenhagen, Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells, J. Physiol. 486 (1995) 207-221] [which are equivalent to our fast AMPA receptor-mediated sEPSCs (fAMPAsEPSCs)], we found another type of AMPA receptor-mediated sEPSC with slower rise and decay time courses and larger peak amplitudes (sAMPAsEPSCs), and the NMDA receptor-mediated sEPSCs (NMDAsEPSCs) in ON-OFF ganglion cells. The frequency of all three types of sEPSCs is greatly reduced by cobalt (with zero calcium) and increased by hyperosmotic solution, suggesting that these events are mediated by calcium-dependent exocytosis of glutamatergic synaptic vesicles. The amplitude histograms of sEPSCs do not show multiple peaks, suggesting that larger events are not discrete multiples of elementary events, or quanta, of similar neurotransmitter contents, as in the neuromuscular junction [P. Fatt, B. Katz, Spontaneous subthreshold activity at motor nerve endings, J. Physiol. 117 (1952) 109-128]. The average I-V relations of the fAMPAsEPSCs and sAMPAsEPSCs were outward rectified with reversal potentials at -12.2 mV and -10.8 mV, and that of the NMDAsEPSCs was N-shaped with a reversal potential at -5.8 mV. The average conductance increase associated with a single fAMPAsEPSC, a single sAMPAsEPSC, and a single NMDAsEPSC were 163. 26+/-51.02 pS, 233.33+/-163.64 pS, and 37.5+/-50.0 pS at -110 mV; 241.67+/-22.92 pS, 444.90+/-469.94 pS, and 25.93+/-70.37 pS at -60 mV; and 440.48+/-183.33 pS, 1,192.68+/-651.22 pS, and 517.71+/-238. 24 pS at +30 mV, respectively. The average frequency of the three sEPSCs at +30 mV were 15 Hz, 3.7 Hz and 3.6 Hz, respectively. The rise time (time to peak) of fAMPAsEPSCs was 1.5+/-1.05 ms and the decay time could be fitted with a single exponential with an average time constant of 3.4+/-4.1 ms. The rise and decay time course of the sAMPAsEPSCs and NMDAsEPSCs were much slower and sawtooth-shaped, and each 'sawtooth' had time course and amplitude similar to those of individual fAMPAsEPSCs. We propose that each fAMPAsEPSC is mediated by single or synchronized multiples of glutamatergic synaptic vesicles from bipolar cells, and each sAMPAsEPSC or NMDAsEPSC is mediated by larger clusters of synaptic vesicles triggered by spontaneous calcium spikes in bipolar cell axon terminals [J. Burrone, L. Lagnado, Electrical resonance and calcium influx in the synaptic terminal of depolarizing bipolar cells from the goldfish retina, J. Physiol. 505 (1997) 571-584; D. Zenisek, G. Matthews, Calcium action potentials in retinal bipolar neurons, Vis. Neurosci. 15 (1998) 69-75].


Acute head-only exposure of dogs to phosgene. Part III. Comparison of indicators of lung injury in dogs and rats.
To better understand the relevance of phosgene-induced changes in bronchoalveolar lavage (BAL) fluid protein observed in acutely exposed rats, groups of beagle dogs were similarly exposed for 30 min to phosgene using a head-only mode of exposure. The actual exposure concentrations were 9, 16.5, and 35 mg/m3, with resultant C x t products of 270, 495, and 1050 mg/m3 x min. In rats, a C x t product of 270 mg/m3 x min caused a significant elevation of protein in the bronchoalveolar lavage (BAL) fluid, while the nonlethal threshold concentration (LCt01) was estimated to be 1075 mg/m3 x min. The endpoints examined in dogs focused on changes in BAL, lung weights, arterial blood gases, and lung histopathology approximately 24 h postexposure. Mortality did not occur at any C x t product. Increased lung weights and elevations in protein, soluble collagen, and polymorphonuclear leukocyte (PMN) counts in BAL were observed at 1050 mg/m3 x min with borderline changes at 495 mg/m3 x min. Following exposure to 1050 mg/m3 x min, the analysis of arterial blood gases provided evidence of a significantly decreased arterial pO2. Histopathology revealed a mild, although distinctive, inflammatory response at the bronchoalveolar level at 495 mg/m3 x min, whereas serofibrinous exudates and edema were observed at 1050 mg/m3 x min. The magnitude of effects correlated with the individual dogs' respiratory minute volume and breathing patterns (panting). Collectively, phosgene-induced indicators of acute lung injury appeared to be characterized best by protein in BAL fluid. With regard to both the inhaled dose and the associated increase of protein in BAL, the responses obtained in dogs appear to be more similar to humans. In contrast, elevations in BAL protein occurred in rats at three-fold lower concentrations when compared to dogs. The results of this study demonstrate that the magnitude of elevations of plasma exudate in BAL fluid following acute exposure to the pulmonary irritant phosgene is markedly more pronounced in rats when compared to the dog which is considered more human-like than rats. This is believed to be associated with the higher ventilation of small rodents and with rodent-specific sensory bronchopulmonary defense reflexes.


Excavating precursors from the traditional Chinese herb Polygala tenuifolia and Gastrodia elata: Synthesis, anticonvulsant activity evaluation of 3,4,5-trimethoxycinnamic acid (TMCA) ester derivatives.
Epilepsy is a group of neurological disorders characterized by recurrent seizures that disturbs about 60 million people worldwide. In this article, a novel series of 3,4,5-trimethoxycinnamic acid (TMCA) ester derivatives 1-35 were designed inspired from the traditional Chinese herb pair drugs Polygala tenuifolia and Gastrodia elata and synthesized followed by in vivo and in silico evaluation of their anticonvulsant potential. All the synthesized derivatives were biologically evaluated for their anticonvulsant potential using two acute model of seizures induced in mice, the maximal electroshock (MES) and sc-pentylenetetrazole (PTZ) models. Simultaneously, the motor impairment as a surrogate of acute neurotoxicity and in vitro screening of cytotoxicity against HepG-2 cells line were assessed through the rotarod performance test and CCK-8 assay, respectively. In addition, the physicochemical and pharmacokinetic parameters of the active compounds were determined. Our results showed that compounds 5, 7, 8, 13, 20, 25, 28, 30 and 32 exhibited preferable anticonvulsant activity in primary evaluation, with compounds 28 and 32 being the most promising anticonvulsant agents in according to results of subsequent pharmacology and toxicity evaluation. Additionally, the molecular modeling experiments predicted good binding interactions of part of the obtained active molecules with the gamma-aminobutyric acid (GABA) transferas. Therefore, it could be concluded that the synthesized derivatives 28 and 32 would represent useful lead compounds for further investigation in the development of anticonvulsant agents.


Lipid composition of membrane microdomains isolated detergent-free from PUFA supplemented RAW264.7 macrophages.
Profound alterations in the lipid profile of raft and non-raft plasma membrane microdomains were found when RAW264.7 macrophages were supplemented with polyunsaturated fatty acids (PUFAs) in physiologically relevant concentrations. For the first time lipids in the detergent-free isolated membrane domains of phagocytic immune cells were characterized by mass spectrometry. The extent of remodeling of the membrane lipids differed with different n3 and n6 PUFA supplements. The mildest effects were detected for α-linolenic acid (LNA) and linoleic acid (LA), the C18 precursors of the n3 and n6 families, respectively. When the effects of highly unsaturated PUFAs were compared, eicosapentaenoic acid (EPA) caused more extensive restructuring of membrane lipids than docosahexaenoic acid (DHA) or arachidonic acid (AA). The supplements altered the lipid species composition of both the raft and non-raft membrane fractions. The rafts containing elevated proportions of highly unsaturated lipid species may relocate sterically incompatible lipids and proteins originally belonging to this microdomain. Such effect was evident for sphingomyelin, which favored non-rafts instead of rafts after EPA supplementation. The current work suggests that the different functional consequences found previously when supplementing macrophages with either EPA or DHA have their origin in the different effects of these PUFAs on membrane architecture.


Auxiliary basis sets for density fitting second-order Møller-Plesset perturbation theory: correlation consistent basis sets for the 5d elements Hf-Pt.
Auxiliary basis sets specifically matched to the correlation consistent cc-pVnZ-PP, cc-pwCVnZ-PP, aug-cc-pVnZ-PP, and aug-cc-pwCVnZ-PP orbital basis sets (used in conjunction with pseudopotentials) for the 5d transition metal elements Hf-Pt have been optimized for use in density fitting second-order Møller-Plesset perturbation theory and other correlated ab initio methods. Calculations of the second-order Møller-Plesset perturbation theory correlation energy, for a test set of small to medium sized molecules, indicate that the density fitting error when utilizing these sets is negligible at three to four orders of magnitude smaller than the orbital basis set incompleteness error.


Solid-phase extraction of plasma vasopressin: evaluation, validation and application.
A new solid-phase extraction method using octyl-silica columns to extract vasopressin-like immunoreactivity from plasma has been developed. The extraction was followed by a radioimmunoassay on the vacuum-dried extracts, which were reconstituted in assay buffer. The total recovery of synthetic vasopressin was ca. 100%. Based on co-elution with synthetic vasopressin after separation by reversed-phase high-performance liquid chromatography of plasma extracts from normal Wistar and Brattleboro rats, and the cross-reactivity of the antiserum used in the radioimmunoassay system, the extracted material was found to be indistinguishable from authentic vasopressin. Unknown experimental samples were interpolated on a standard curve established in "zero" plasma (plasma derived from rats subjected to waterload) spiked with known amounts of synthetic vasopressin, and not on a standard curve established in assay buffer. The limit of detection was 1 fmol of vasopressin equivalent per millilitre. The intra- and inter-assay coefficients of variance were 10-16% and 16%, respectively. The procedure reliably showed that osmotic challenge and 24-h dehydration increased, whereas ethanol ingestion decreased vasopressin-like immunoreactivity plasma levels in the rat, compared with normally hydrated controls.


Perceptual and Semantic Phases of Face Identification Processing: A Multivariate Electroencephalography Study.
Rapid identification of a familiar face requires an image-invariant representation of person identity. A varying sample of familiar faces is necessary to disentangle image-level from person-level processing. We investigated the time course of face identity processing using a multivariate electroencephalography analysis. Participants saw ambient exemplars of celebrity faces that differed in pose, lighting, hairstyle, and so forth. A name prime preceded a face on half of the trials to preactivate person-specific information, whereas a neutral prime was used on the remaining half. This manipulation helped dissociate perceptual- and semantic-based identification. Two time intervals within the post-face onset electroencephalography epoch were sensitive to person identity. The early perceptual phase spanned 110-228 msec and was not modulated by the name prime. The late semantic phase spanned 252-1000 msec and was sensitive to person knowledge activated by the name prime. Within this late phase, the identity response occurred earlier in time (300-600 msec) for the name prime with a scalp topography similar to the FN400 ERP. This may reflect a matching of the person primed in memory with the face on the screen. Following a neutral prime, the identity response occurred later in time (500-800 msec) with a scalp topography similar to the P600f ERP. This may reflect activation of semantic knowledge associated with the identity. Our results suggest that processing of identity begins early (110 msec), with some tolerance to image-level variations, and then progresses in stages sensitive to perceptual and then to semantic features.


Adhesion contact dynamics of 3T3 fibroblasts on poly (lactide-co-glycolide acid) surface modified by photochemical immobilization of biomacromolecules.
A simple and effective method of biomacromolecule immobilization on biomaterial surface for direct tuning of biophysical parameters such as the initial cell deformation rate, degree of cell spreading and adhesion kinetics is important for tissue engineering. The photochemical immobilization of azide-chitosan (Az-CS) on poly (lactide-co-glycolide) acid (PLGA) is applied here. Chitosan immobilization on PLGA through the photoactive azide group further facilitates subsequent grafting of other biocompatible biomacromolecules like gelatin (Gel) through the active amine groups on CS. This study quantitatively compares the 3T3 fibroblast adhesion dynamics on three PLGA surfaces (Gel-CS-PLGA, CS-PLGA and unmodified PLGA surfaces) using Confocal-Reflectance Interference Contrast Microscopy (C-RICM) together with phase contrast imaging. CS-PLGA and Gel-CS-PLGA surfaces developed were confirmed by X-ray photoelectron spectroscopy, atomic force microscopy and water contact angle and cell adhesion contact dynamics measurements. The cell adhesion was strongest on the Gel-CS-PLGA surface and lowest on unmodified PLGA. The steady state adhesion energy attained by the cells on gelatin modified PLGA surface is determined as 4.0 x 10(-8) J/m(2), which is about 400 times higher than that on PLGA surface (1.1 x 10(-10) J/m(2)). Significantly increased cell adhesion with Gel-CS-PLGA is postulated to result in increased cell spreading. Our integrated biophysical method can quantify the transient contact dynamics and is sufficiently accurate to discriminate even between Gel and CS modified surfaces.


The distressed (Type D) personality is independently associated with tinnitus: a case-control study.
Tinnitus is a common and disturbing condition, reported by 10% to 20% of the general population. The authors sought to determine personality characteristics associated with tinnitus patients versus a control group of ear-nose-throat (ENT) patients without tinnitus. Adult chronic tinnitus sufferers (N=265) and ENT patients without tinnitus (N=265) participated in a cross-sectional study. The authors evaluated personality characteristics with tests for distressed personality (Type D), neuroticism, extraversion, and emotional stability. As compared with control subjects, tinnitus patients had statistically significant and clinically relevant higher levels of neuroticism, negative affectivity, and social inhibition, on one hand, and lower levels of extraversion and emotional stability on the other hand. Also, tinnitus patients were more likely to have a type D personality. Neuroticism, reduced extraversion, and reduced emotional stability were associated with tinnitus, but the level of prediction of the model improved with the addition of type D personality to the single traits. This might indicate that personality characteristics, and type D personality, in particular, are associated with having tinnitus and might contribute to its perceived severity.


Evaluation of the All Stars character education and problem behavior prevention program: effects on mediator and outcome variables for middle school students.
The effects of All Stars, a character education and problem behavior prevention program, on variables theorized to mediate problem behaviors and on the problem behavior variables of substance use, sexual behavior, and violence among middle school students are reported. In an independent, randomized, single-cohort, longitudinal evaluation of the program, 1,655 students completed pretest, posttest, and 1-year follow-up surveys measuring demographics, mediating variables, and behavioral outcome variables. Results indicate that the All Stars program, when administered by teachers, had an immediate effect on mediating variables that did not persist over time. Inclusion of ethnicity in the design showed that the program, when administered by specialists, had delayed effects on mediating variables for African American and Hispanic students. However, no consistent effects were found for student problem behaviors in either condition. Implications for prevention practice and directions for future research are discussed.


Solution structure of an 11-mer duplex containing the 3, N(4)-ethenocytosine adduct opposite 2'-deoxycytidine: implications for the recognition of exocyclic lesions by DNA glycosylases.
Lipid peroxidation products, as well as the metabolic products of vinyl chloride, react with cellular DNA producing the mutagenic adduct 3,N(4)-etheno-2'-deoxycytidine (epsilondC), along with several other exocyclic derivatives. High-resolution NMR spectroscopy and restrained molecular dynamics simulations were used to establish the solution structure of an 11-mer duplex containing an epsilondC.dC base-pair at its center. The NMR data suggested a regular right-handed helical structure having all residues in the anti orientation around the glycosydic torsion angle and Watson-Crick alignments for all canonical base-pairs of the duplex. Restrained molecular dynamics generated a three-dimensional model in excellent agreement with the spectroscopic data. The (epsilondC. dC)-duplex structure is a regular right-handed helix with a slight bend at the lesion site and no severe distortions of the sugar-phosphate backbone. The epsilondC adduct and its partner dC were displaced towards opposite grooves of the helix, resulting in a lesion-containing base-pair that was highly sheared but stabilized to some degree by the formation of a single hydrogen bond. Such a sheared base-pair alignment at the lesion site was previously observed for epsilondC.dG and epsilondC.T duplexes, and was also present in the crystal structures of duplexes containing dG.T and dG. U mismatches. These observations suggest the existence of a substrate structural motif that may be recognized by specific DNA glycosylases during the process of base excision repair.


Central nervous system arteriovenous malformations with hereditary hemorrhagic telangiectasia: report of a family with three cases.
A family with central nervous system (CNS) arteriovenous malformations (AVMs) and hereditary hemorrhagic telangiectasia (HHT) is reported. A 46-year-old man had an intracerebral hemorrhage. Cerebral angiography showed one AVM and two angiomas. The HHT was diagnosed because of the concomitant existence of cutaneous telangiectasia. The patient's brother had HHT and paraplegia since the age of 21. Magnetic resonance imaging revealed an old spinal cord hemorrhage. The patient's son with HHT had an intracerebral hemorrhage at age 6. Angiograms showed two AVMs and one angioma. Familial CNS AVMs with HHT are extremely rare. The loci for human leukocyte antigen of the affected cases with HHT were evaluated, and the management of CNS AVMs with HHT is discussed.


A presenter's view of partnering with providers.
This column offers a snapshot of the presenter's perspective of providing continuing education activities.


[Digital subtraction angiocardiography: reliability of densitometric determination of left ventricular volume and ejection fraction].
The angiographic assessment of left ventricular volume (LV) and ejection fraction (EF) by means of the area-length method (ALM) is based upon geometric assumptions, which might lead to erroneous results. With the development of digital subtraction angiocardiography in real-time, densitometric procedures of calculating left ventricular parameters can be used on-line. This study examines both reliability and accuracy of a densitometric technique for evaluating LV and EF in comparison to the single-plane ALM. Contrast images of heart casts and left ventricular angiograms of 54 patients suffering from different cardiac diseases were obtained by the image acquisition and processing system Polytron 1000 VR (Siemens AG, Erlangen, FRG). Digital images of both heart casts and patients were evaluated densitometrically and geometrically by two independent observers. In the phantom study the densitometric method exhibited a significantly (p < 0.01) better agreement with the true values than the ALM. The evaluation of left ventricular angiograms in patients comparing densitometry with the ALM demonstrated a relatively high residual deviation (enddiastolic volume Syx = +/- 27 ml, endsystolic volume Syx = +/- 19.4 ml). This is mainly due to systematic, method-related errors of densitometry and the morphometric technique. The intra- and interobserver variability in calculating EF showed a significantly (p < 0.05) smaller residual deviation for densitometry than for ALM; no significant differences were found for the calculation of LV. In conclusion, we demonstrated that the presented densitometric technique offers an objective and simple means of determining LV and EF with comparable reliability and validity to the area-length method.


Evolving perception on the benefits of vaccination as a foot and mouth disease control policy: contributions of South America.
Within the past decade, changes in perceptions on the benefits of vaccination as an appropriate tool to achieve complete foot and mouth disease eradication have become evident. The former negative view was derived from misconceptions, resulting mainly from the belief that vaccines are not entirely effective and that vaccination masks asymptomatic viral circulation. The advent in the 1990s of vaccination policies implemented within a strategic eradication plan in South America, and during recurrence of the disease in disease-free regions contributed towards generating more reliable and visible outcomes of vaccination programs, paving the way towards a new perception. Particularly relevant was the development and application of novel serodiagnostic approaches to assess silent viral circulation, irrespective of vaccination. The use in South America of vaccination allied to serosurveys to accompany viral clarification during eradication campaigns and after emergencies clearly established the importance of this control tool to stop the spread of viral infection. This alliance gave input to break many myths associated with the use of vaccines, including the belief that immunized carrier animals pose an epidemiologic risk. This experience launched new concepts that supported the internationally recognized status of foot and mouth disease-free regions with vaccination and the 'vaccination to live' policy as an alternative to 'stamping out'.


Beyond the Anomaly: Where Piaget and Bruner Meet.
The aim of this work is to focus on a basic concept in Brunerian narrative theory, that of violation of canonicity, showing how it relates to other basic concepts of cognitive theories such as anomaly, expectation and relationship between constancy and variability. To reach this aim, we will firstly discuss the Piagetian theory, in particular regarding the way in which the child deals with new and interesting events moved from the need to face and produce "spectacles interessantes" by means of experiencing the violation of canonicity. We will also briefly consider some results of neurosciences studies pointing out that the constancy-variability issue is at the base of human development. Secondly, we will show the convergence between Piagetian theory and Brunerian theory of narration, producing some examples of how violation of canonicity can occur in children and adults.


Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using UGT1A1 Genotype-Guided Dosing.
5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype-guided dosing of irinotecan. Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure. Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks. FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.


Cost/effectiveness ratio of carcinoembryonic antigen--importance of adequacy of routine requests of tumor markers.
Since 1987 we have been evaluating the cost/effectiveness ratio of tumor markers using carcinoembryonic antigen (CEA) as a leading indicator. Preliminary to the evaluation of cost/effectiveness ratio we verified the fitness of CEA requests to the proper clinical problems in order to identify any bias of cost due to inadequate CEA use. 2677 CEA orders were evaluated in 1987. The percentage of inadequate requests was very high (43%). Therefore, it seemed not advisable to carry out the evaluation of cost/effectiveness ratio, while educational actions (divulgation of informative material, service of telephone consultation) were addressed to the physicians of the geographic area of laboratory users. In 1991 the adequacy of CEA requests was reevaluated. The percentage of inadequate requests on 2647 orders was 29.4%. This result, although not yet satisfactory, suggests that proper educational programs may probably improve the fitness of tumor marker requests to correct clinical problems. Additional educational actions are mandatory to further reduce the rate of inadequate tumor marker orders.


Occlusal contacts following orthodontic treatment: a follow-up study.
Occlusal contacts in maximum intercuspation were examined in a sample of 40 patients at the end of active orthodontic treatment and again an average of 21 months later. An increase in the total number of contacts was due to more actual and near contacts on all posterior teeth and more near contacts on anterior teeth. When the results were compared to a previous short term study, continued settling of the occlusion occurred beyond an initial three months of retention. Few contacts changed their location between the occlusal inclined planes and central grooves, suggesting minimal settling of the occlusion in a buccolingual direction.


PAES and PAHs in the surface sediments of the East China Sea: Occurrence, distribution and influence factors.
A total of 29 sediment samples were collected from the East China Sea (ECS), with the Yangtze River estuary and the Zhejiang costal area. These sediment samples were analyzed for 6 phthalate esters (PAEs) and 16 polycyclic aromatic hydrocarbons (PAHs): the ΣPAEs and ΣPAHs concentrations ranged between 1649.5 and 8451.5 ng g-1 (mean = 3446.3 ng g-1) and 57.5-364.5 ng g-1 (mean = 166.2 ng g-1), respectively. Overall, the PAEs and PAHs concentrations gradually decreasing in the offshore and southward directions: their compositions and distributions suggest they could have mainly derived from the Yangtze River. In particular, their distribution was influenced by the sources' proximity, hydrodynamics, and sediment geochemistry (i.e., TOC content and grain size). A classical two-end member model was utilized to estimate the fraction of terrestrial organic carbon in the sediments of the ECS. When the sediment was dominated by terrestrial-derived organic matter (OM), the concentrations of PAEs and PAHs were significantly correlated to the TOC content and gran size of the sediments. In contrast, the poor correlation of TOC content and grain size with PAEs in those sediments dominated by marine-derived OM, implied that the distribution of PAEs in the ECS was mainly related to land-based inputs, (especially to that of the Yangtze River). Regardless of the origin of most of the OM contained in the sediments, we observed positive correlations between the TOC content, and grain size of those containing PAHs. These results suggest that the distribution of PAHs in the ECS was not only related to the Yangtze River input, but also to the geochemical characteristics of the sediments.


Mouse lacking NAD+-linked glycerol phosphate dehydrogenase has normal pancreatic beta cell function but abnormal metabolite pattern in skeletal muscle.
We surveyed the BALB/cHeA mouse, which lacks cytosolic glycerol phosphate dehydrogenase an enzyme that catalyzes a reaction in the glycerol phosphate shuttle. The other enzyme of this shuttle, mitochondrial glycerol phosphate dehydrogenase, is abundant in skeletal muscle and pancreatic islets suggesting that the shuttle's activity is high in these tissues. Levels of glycerol phosphate (low) and dihydroxyacetone phosphate (high) were very abnormal in nonislet tissue, especially in skeletal muscle. Intermediates situated before the triose phosphates in the glycolysis pathway were increased and those after the triose phosphates were generally low, depending on the tissue. The lactate/pyruvate ratio in muscle was low signifying a low cytosolic NAD/NADH ratio. This suggests that a nonfunctional glycerol phosphate shuttle caused a block in glycolysis at the step catalyzed by glyceraldehyde phosphate dehydrogenase. When exercised, mice were unable to maintain normal ATP levels in skeletal muscle. Blood glucose, serum insulin levels, and pancreatic islet mass were normal. In isolated pancreatic islets insulin release, glucose metabolism and ATP levels were normal, but lactate levels and lactate/pyruvate ratios with a glucose load were slightly abnormal. The BALB/cHeA mouse can maintain NAD/ NADH ratios sufficient to function normally under most conditions, but the redox state is not normal. Glycerol phosphate is apparently formed at a slow rate. Skeletal muscle is severely affected probably because it is dependent on the glycerol phosphate shuttle more than other tissues. It most likely utilizes glycerol phosphate rapidly and, due to the absence of glycerol kinase in muscle, is unable to rapidly form glycerol phosphate from glycerol. Glycerol kinase is also absent in the pancreatic insulin cell, but this cell's function is essentially normal probably because of redundancy of NAD(H) shuttles.


Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.
We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.


Variation in the Azotobacter population from several habitats in the botanical garden in Poznań.
The abundance of Azotobacter was estimated in the rhizosphere of 13 plant species from four habitats in the Botanical Garden in Poznań. The results have shown that within the particular habitats the plant exerts a pronounced influence on the abundance of Azotobacter. The morphological differences between Azotobacter populations obtained from various habitats confirm the specific effect of the plant on this bacterium.


Cholesterol absorption and turnover in rhesus monkeys as measured by two methods.
We compared the absorption of cholesterol in seven rhesus monkeys (four high-responders and three low-responders) as measured by two methods: 1) the dual isotope plasma ratio method of Zilversmit (1972. Proc. Soc. Exp. Biol. Med. 140: 862) and 2) the single isotopic meal feeding technique of Borgström (1969. J. Lipid Res. 10: 331). We also compared the cholesterol pool sizes calculated by kinetic analysis of the plasma cholesterol specific activity decay curves obtained after simultaneous administration of [(3)H]- and [(14)C]cholesterol, one given intravenously and the other orally. The ratio of orally to intravenously administered cholesterol radioactivity in plasma did not attain constancy until 6 weeks after isotope administration. Therefore, the percent absorption of cholesterol was calculated by the Zilversmit method 8 weeks after the administration of isotopes. The mean percent absorption of cholesterol by the Borgström method was 66.3 +/- 5.1 (S.E.) and by the Zilversmit method was 70.3 +/- 7.4. The differences were not statistically significant. However, in two of seven monkeys the percent absorption of cholesterol calculated by the Zilversmit method was higher by 10.4 and 22.6 percentage points than the values obtained by the Borgström method. Cholesterol absorption by either method was higher in the high-responding monkeys than in the low-responding group. The sizes of the rapidly exchangeable pool or the minimum estimate of the total body pool of cholesterol were similar for all monkeys or for either the low-responding or the high-responding animals and were also similar when calculated using the data from either the orally or the intravenously administered radioactive cholesterol. Cholesterol synthesis was significantly higher in the low-responding monkeys (115 mg/day) than in the high-responding (64 mg/day). The present study and our previous studies support the hypothesis that a major factor causing the difference in response of plasma cholesterol to dietary cholesterol between the high- and low-responding rhesus monkeys is a difference in the intestinal absorption of cholesterol.-Bhattacharyya, A. K., and D. A. Eggen. Cholesterol absorption and turnover in rhesus monkeys as measured by two methods.


Bionic larynx: electronic control of the reimplanted organ in the dog.
Complete rehabilitation of paralyzed head and neck structures has been difficult, and attempts at reinnervation of striated muscles have not consistently succeeded. Recent studies have shown that disabled muscles can be electronically "paced." This, together with recent developments in microelectronics, has led to the concept of the Bionic Larynx. The current experiments involve transposed nerve-muscle pedicles used to selectively reinnervate larynges which were denervated, entirely detached from the animal except for their vascular supply, and then reimplanted. These pedicles were later stimulated using a potentially implantable "pacing unit." It was possible to selectively control the critical functions of the larynx, using as stimuli physiological events that are preserved even when the vocal folds are paralyzed or uncoordinated. Although laryngeal transplantation in humans remains theoretical, these studies show that it could be feasible in the future.


An homologous in vitro assay for yeast nonsense suppressors.
A cell-free translation system, from the yeast Saccharomyces cerevisiae, has been used to develop an in vitro assay for yeast UGA, ochre and amber suppressors. Amber suppression was assayed by read-through of the brome mosaic virus coat protein cistron UAG terminator. UGA suppression was assayed by read-through of the rabbit beta-globin UGA terminator and ochre suppression by read-through of the rabbit alpha-globin mRNA UAA terminator. Ochre suppression was increased 3-fold when the globin mRNA was heat denatured prior to translation; this was due to an increase in the synthesis of alpha-globin relative to beta-globin. Amber suppression was more efficient in vitro (46%) than ochre suppression (14%). UGA suppression was also highly efficient in vitro, reaching almost 100% using a purified UGA suppressor tRNA from Schizosaccharomyces pombe. Unfractionated yeast tRNA, from a sup+ strain, contained a tRNA species able to suppress UGA termination codons in vitro, but no tRNA species able to suppress either UAA or UAG was found. This homologous in vitro assay for yeast nonsense suppressors will allow, for the first time, an approach to the biochemical analysis of yeast mutants that modify the efficiency of nonsense suppression in vivo.


Survey of gastrointestinal endoscope disinfection and accessory reprocessing practices in the Asia-Pacific region.
Concern has been raised about the possibility of transmission of infection by gastrointestinal endoscope. This vexation may be related to reliability of the disinfecting techniques or to the compliance with the guidelines laid down for disinfection. There have been very few recent surveys examining the disinfection practices for gastrointestinal endoscopes and their accessories. This survey was undertaken to understand such practices in the Asia-Pacific region. A questionnaire was sent by post or electronic mail to 356 randomly selected endoscopy centres in the Asia-Pacific region. Responses were received from 38.7% of the centres. The survey showed that there were significant aberrations in the application of disinfection procedures. One-third of the respondents did not practise disinfection at the start of the day's session, 2.9% of the centres were not using a high-level disinfectant and 34.7% of the centres used a soak time in 2% glutaraldehyde of less than 10 min. At 40% of the centres, at the end of the day's session, forced air or alcohol was not used to dry the endoscopes. Reuse of accessories meant for single use was widely practised.


Evaluation of an acute pain service.
Implementation of an acute pain nurse role and the expansion of the Acute Pain Service (APS) at a newly merged Canadian hospital system led to an evaluation of these programs. A literature review of APSs showed that the services with an APS nurse had improved patient outcomes. As a result, a PACU nurse was added to the APS at all hospitals, and all services were restructured. Surveys conducted one year after this reorganization showed very positive response ratings in the areas of quality of care, but mixed results in other areas including education and job satisfaction. Flow diagrams for the clinical units were developed, and both structured and informal education sessions were provided. The description of the APS nurse's role was also redefined.


Sources of guns to dangerous people: what we learn by asking them.
Gun violence exacts a lethal toll on public health. This paper focuses on reducing access to firearms by dangerous offenders, contributing original empirical data on the gun transactions that arm offenders in Chicago. Conducted in the fall of 2013, analysis of an open-ended survey of 99 inmates of Cook County Jail focuses on a subset of violence-prone individuals with the goal of improving law enforcement actions. Among our principal findings: *Our respondents (adult offenders living in Chicago or nearby) obtain most of their guns from their social network of personal connections. Rarely is the proximate source either direct purchase from a gun store, or theft. *Only about 60% of guns in the possession of respondents were obtained by purchase or trade. Other common arrangements include sharing guns and holding guns for others. *About one in seven respondents report selling guns, but in only a few cases as a regular source of income. *Gangs continue to play some role in Chicago in organizing gun buys and in distributing guns to members as needed. *The Chicago Police Department has a considerable effect on the workings of the underground gun market through deterrence. Transactions with strangers and less-trusted associates are limited by concerns over arrest risk (if the buyer should happen to be an undercover officer or a snitch), and about being caught with a "dirty" gun (one that has been fired in a crime).


Intensity modulated radiation therapy: film verification of planar dose maps.
A new slow response radiographic film (Kodak EDR) is compared with a more traditional faster responding dosimetry film (Kodak XV) in an intensity modulated radiation therapy x-ray field. Dose profiles derived from the two films are compared with doses obtained using a radiotherapy dose planning system (Philips-Pinnacle) which calculates planar dose using a collapsed cone convolution algorithm. Comparisons of the dose maps delivered from film with the Pinnacle dose maps are useful to ensure accurate dose delivery. The Pinnacle dose maps agreed with measurement using both film types to within +/- 3% (in the umbral region) at depths ranging from d(max) to 15 cm. Both XV and EDR films can be used to verify IMRT. EDR film is better suited for dosimetry for combined field dose maps due to its useful dose range of 1-5 Gy. We found XV to be more suitable for individual field dose maps (dose range 0-1 Gy) as no scaling of monitor units were required to achieve acceptable optical density response.


Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand in normal human osteoblasts via the p38 mitogen-activated protein kinase pathway by the application of cyclic tensile strain.
Mechanical stress is thought to play an important role in bone remodeling. However, the correlation between mechanical stress and bone remodeling is poorly understood. In this context, using a model of cyclic tensile strain (CTS) toward human osteoblasts, synthesis of osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and the activation of mitogen-activated protein kinases (MAPKs) were examined. The application of 7%, 0.25-Hz CTS once a day for 4 h for 3 successive days simultaneously caused an increase of OPG synthesis and a decrease of sRANKL release and RANKL mRNA expression in osteoblasts. As for MAPKs activation in osteoblasts with the application of CTS, p38 MAPK was activated 10-20 min after the application of CTS, but extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) were not activated by such application. Furthermore, when CTS was applied once a day for 4 h for 1, 2, or 3 successive days to osteoblasts, p38 MAPK activation was maintained during the 3-day period but ERK1/2 activation was downregulated from day to day, simultaneously. Then, when CTS was applied once a day for 4 h for 3 successive days to osteoblasts pretreated with the p38 MAPK inhibitor SB203580 for 1 h, OPG synthesis was dose-dependently suppressed and inhibition of sRANKL release and RANKL mRNA expression was abrogated. These results indicate that biological responses of OPG and sRANKL synthesis in osteoblasts to the application of CTS are regulated via the p38 MAPK pathway and suggest that CTS might modulate and regulate bone metabolism.