Incremental employee health benefit costs, absence days, and turnover among employees with ADHD and among employees with children with ADHD.
To assess employer economic burden of attention-deficit/hyperactivity disorder (ADHD) for employees with ADHD and employee caregivers of children with ADHD. A large multi-employer database was used to compare: 1) employees diagnosed with ADHD versus employees without ADHD and 2) employee caregivers of children with ADHD versus employee caregivers of children without ADHD. Regression modeling compared many employer-relevant outcomes. The study found significantly higher annual health benefit costs ($6885 versus $4242), absence days (8.86 versus 7.16), and turnover (8.99% versus 5.26%) for employees with ADHD (n = 539) versus employees without ADHD (n = 93,722), respectively (all P < 0.01). Similar results were found for employee caregivers of children with ADHD. Employees with ADHD and those caring for children with ADHD are associated with a significantly higher burden in employer-relevant outcomes such as health benefit costs, absences, and terminations.


Impact of WWII dumpsites on Saipan (CNMI): heavy metal status of soils and sediments.
A number of dumpsites occur on the island of Saipan and in the surrounding coastal waters. Many of these sites date back to the immediate post WWII clean-up period and contain a variety of wartime wastes. Metallic debris is generally the most visible waste material and commonly includes bomb fragments, artillery shells, bullets, and other military hardware. In this investigation, we examined the heavy metal status of soils from around several of these dumpsites and in any obvious drainage pathways leading from them to the coast. Sediments were also taken for analysis from a number of coastal discharge points and three submerged sites. Metal enrichment was evident for one or more elements in deposits from two of the three submerged sites and 24 of the 32 land-based sites visited. Copper, Pb, and Zn were the most commonly encountered contaminant metals with levels well in excess of 1000 μg/g(-1) in several instances. Elevated Hg and Cd concentrations were also relatively widespread throughout the study area although levels of each element seldom exceeded 1.0 and 10.0 μg/g(-1), respectively. Silver, another element of toxicological concern, was only occasionally detected despite registering a high of 42 μg/g(-1) at one particular site. The metal data were weighed against established benchmarks formulated for the protection of human and ecological health. Implications of the findings and issues of primary concern are briefly addressed.


[Factors influencing problem and pathological gambling in participants of horse race gambling].
The purpose of this study was to examine risk factors for pathological gambling of horse race participants. The participants, 508 horse race gamblers, completed the DSM-IV criteria of pathological gambling, Alcohol Use Disorders Identification Test (AUDIT-K) and Symptom Checklist-47-Revision (SCL-47-R). Data were analyzed using t-test, χ²-test, Fisher's exact test, and logistic regression analyses. Behaviors related to horse racing, alcohol abuse, and mental health were analyzed between problem or pathological gamblers compared to recreational gamblers. The prevalence rates of recreational, problem, and pathological gambling were 36.6%, 39.4%, and 24.0%, respectively. Frequency of gambling (≥4/day), frequency of racetrack visiting (≥3/month), accompaniment (alone), and mental health (SCL-47-R scores) were all associated with increased risks of problem and pathological gambling. Expenditure on betting (≥200,000 won/day) and alcohol abuse (AUDIT-K 8-20 scores) group members had higher levels of gambling pathology than recreational gamblers. Problem and pathological gambling are highly associated with alcohol abuse and mental health disorders, suggesting that clinicians should carefully evaluate this population.


[Psychiatric aid during the Great Patriotic War].
The article presents an observe of questions of organization of psychiatric aid during the Great Patriotic War, main disadvantages of the first period of war, their dependence from circumstances of prewar period, ignoring of experience of last war. There was marked the role of famous native psychiatrists in organization of psychiatric aid to military servicemen in theatre of combat actions.


Day-case adenoidectomy: how popular and safe in a rural environment?
In spite of previously favourable reports on day-case adenoidectomy, there are still worries amongst otolaryngologists that such practice is unsafe, especially in a rural environment. A national survey was therefore carried out which shows that only 41 per cent of respondents perform adenoidectomy routinely as day-case, and even fewer in rural areas. A regional audit on day-case adenoidectomy, covering five hospitals, was conducted in East Anglia. Between 1994 to 1995, 73 day-case adenoidectomies were performed and the outcome was compared to those of 183 in-patient adenoidectomies during the same period. The children in the day-case group recovered post-operatively even better than the in-patient group. None of them stayed overnight or required re-admission. There was no increased in post-operative consultation to the general practitioner. The parents in the day-case group were mostly in favour of the day-case arrangement (88 per cent). The results suggest that day-case adenoidectomy is safe and popular with parents even in a rural environment.


A Qualitative Study of Community-Based HIV/AIDS Prevention Interventions, Programs, and Projects for Rural and Remote Regions in Canada: Implementation Challenges and Lessons Learned.
Fifteen percent to 20% of the Canadian and American populations live outside urban areas, and despite growing regional HIV/AIDS-related health disparities, there is little published research specific to rural or remote (rural/remote) HIV/AIDS prevention programming. To document implementation challenges, lessons learned, and evaluation approaches of promising and proven HIV/AIDS prevention programs and interventions developed and delivered by organizations with rural/remote catchment areas in Canada to provide a foundation for information sharing among agencies. Qualitative study design, using a community-based participatory research approach. We screened Canadian community-based organizations with an HIV/AIDS prevention mandate to determine whether they offered services for rural/remote populations and invited organizational representatives to participate in semistructured telephone interviews. Interviews were audio-recorded and transcribed. Content analysis was used to identify categories in the interview data. Canada, provinces (all except Prince Edward Island), and territories (all except Nunavut). Twenty-four community-based organizations. Screening calls were completed with 74 organizations, of which 39 met study criteria. Twenty-four (62%) interviews were conducted. Populations most frequently served were Indigenous peoples (n = 13 organizations) and people who use drugs (n = 8 organizations) (categories not mutually exclusive). Key lessons learned included the importance of involving potential communities served in program development; prioritizing community allies/partnerships; building relationships; local relevancy and appropriateness; assessing community awareness or readiness; program flexibility/adaptability; and addressing stigma. Evaluation activities were varied and used for funder reporting and organizational learning. Rural/remote HIV/AIDS programs across Canada expressed similar challenges and lessons learned, suggesting that there is potential for knowledge exchange, and development of a community of practice. Top-down planning and evaluation models may fail to capture program achievements in rural/remote contexts. The long-term engagement practices that render rural/remote programs promising do not always conform to planning and implementation requirements of limited funding.


Evaluating pain and disability.
This article has attempted to present an overview of how pain and disability interact, the incidence and cost of disability secondary to painful conditions, a review of the current disability systems, how pain should be evaluated, and some thoughts on the future of disability and pain. Most people are unhappy with the present process from an administrative, logistical, and cost-effective point of view. However, there is a continuing concern that change will be driven largely by cost containment rather than other important aspects of disability.


[Transposition bursts in analysis of repeated mutations in unstable strains of Drosophila melanogaster].
The phenomenon of transposition memory was earlier demonstrated for the cut locus and mdg4. This work has been aimed at finding out, in what way the transposition memory can be realized. An unstable stock cmMR17ctMRpN17 was analysed which had high frequency of double cm+ct+ reversions and cmMRctMRpN repeated mutations. A series of five such transpositions could be followed. The ctMRpN17 mutation is a result of insertion at the cut locus mdg4 with the jockey element inserted within it. As seen from in situ hybridization analysis, transitions to the normal phenotype correlate, as a rule, with the excision of mdg4 and the jockey from the cut locus. Analysis of distribution of mdg1, mdg2, mdg3 and jockey on the X-chromosome of unstable revertants and repeated mutants indicated that not only transpositions of mdg4 and jockey, but also those of all mobile elements tested occur. So, we propose that the transposition memory in our genetic system is manifested in the process of transposition bursts.


Lag screw and cancellous bone graft fixation of transverse proximal sesamoid bone fractures in horses: 25 cases (1983-1989).
Case records of 25 horses with transverse fractures of the proximal sesamoid bone were reviewed to evaluate the success of treatment. All fractures were repaired by use of lag screw fixation and an autogenous cancellous bone graft because the fracture fragments were considered too large for surgical removal and reconstruction of the suspensory apparatus was necessary. Radiography was performed in all cases, and the fractures were classified into 3 types: (1) proximal midbody fractures, which included all fractures in the proximal aspect of the sesamoid bone that resulted in fragments involving greater than one third but less than one half of the total mass of the sesamoid bone; (2) midbody fractures that divided the bone into 2 equal portions; and (3) distal midbody fractures, which included transverse fractures in the distal aspect of the sesamoid bone that resulted in fragments involving greater than one third but less than one half of the total mass of the sesamoid bone. Of these cases, race records were obtained for 9 Standardbreds and 5 Thoroughbreds. Postoperative performance criteria evaluated were the ability to train and start 1 race, ability to maintain preinjury class of racing, earnings per start, and the number of starts following surgery. In Thoroughbreds, fractures occurred most commonly in the right forelimb; in Standardbreds, the left hind limb was most commonly involved. The midbody fracture was the most common type in both breeds, and the distribution of fracture location within the sesamoid bone was similar for both breeds.(ABSTRACT TRUNCATED AT 250 WORDS)


A methodologic analysis of chemoprevention and cancer prevention strategies for gastrointestinal cancer.
Gastroenterology lags behind other specialties such as cardiology in the quality of its evidence base for clinical practice. One area where this is particularly evident is in cancer prevention, despite developments in chemoprevention strategies for high-risk patients. For chemoprevention strategies to be successful, we need appropriate clinical networks and translational science infrastructures, model chemoprevention agents and multiple, large, flexible and randomized clinical trials. Translational science must also be embedded into large-scale, long-term, randomized clinical trials that have hard endpoints, so that irrefutable evidence of the longevity of treatment efficacy can be gathered. We also need to be able to identify an individual's cancer risk using valid global patient populations, so that medical benefits can be applied to all, regardless of ethnicity, sex, economic status, age and comorbidities. The future success of gastrointestinal chemoprevention relies on fostering a closer link between basic pharmaceutical research and clinical applications, in a 'bench to bedside and back' manner. In this review we systematically assess the evidence for various cancer prevention strategies, especially chemoprevention, and highlight the obstacles to further exploitation of this knowledge base.


Contamination of donor cornea: postpenetrating keratoplasty endophthalmitis.
Nine cases (0.41%) of bacterial and fungal endophthalmitis developed out of a total of 2,210 consecutive penetrating keratoplasties performed between November 1983 and April 1989. Five of the nine cases (0.23%) had endophthalmitis related to donor tissue contamination. The donor tissue of these cases had a storage time of greater than 5 days. A retrospective analysis of 1,399 consecutive corneoscleral rim cultures showed a contamination rate of 29%. The most common organisms isolated were Propionibacterium 26%, diphtheroids 24%, Staphylococcus epidermidis 22%, and fungi 9%. There is a statistically significant increase (p less than 0.005) in the percentage of contaminated donor rims with a preservation time of more than five days. The risk of developing endophthalmitis is 12 times greater with a positive donor rim culture. Prolonged preservation of donor tissue can be a risk factor in developing endophthalmitis.


Disturbance of autoregulation in patients with ruptured intracranial aneurysms: mechanism of cortical and motor dysfunction.
Serial measurements of local cerebral blood flow were obtained with inhalation of stable xenon and computed tomography prior to and during induced hypertension with continuous infusion of dopamine (7-15 micrograms/kg/min) in 34 patients who underwent surgery for treatment of subarachnoid hemorrhage due to ruptured intracranial aneurysm. Cerebral vasospasm was detected angiographically in all but one of the patients studied. Vasospasm was not symptomatic in 19 patients, but was in the other 15 patients. Disturbance of autoregulation was observed just after surgical operation. In the latter group, local cerebral blood flow in the territory of the middle cerebral artery and the corona radiata on the craniotomy side reached their lowest values, 25.1 +/- 6.8 mL/100 g/min and 15.7 +/- 1.8 mL/100 g/min, respectively, on days 10-14, and each subsequently increased significantly, to 34.3 +/- 7.3 mL/100 g/min and 19.9 +/- 2.0 mL/100 g/min, respectively, during induced hypertension. In conclusion, cortical dysfunction and motor palsy in the patients studied here were thought to be due to significant reduction in local cerebral blood flow in the cortical territories of the middle cerebral artery and corona radiata, respectively.


Torsional stiffness of three spine constructs for thoracic scoliosis.
The standard two-rod thoracic scoliosis construct is bulky in the thin, young patient. A single-rod construct with hooks at every level was developed. Five calf spines were tested measuring angular displacement before and after instrumentation using three scoliosis constructs: a standard two-rod construct, a single-rod construct, and a single-rod construct with crossover hooks. Rotational displacements and stiffness were compared. There was no statistical difference in rotational displacement or stiffness among the three constructs. All three constructs were significantly stiffer in torsion than the uninstrumented control. The single-rod construct and the crossover construct may offer the spine surgeon additional options in instrumenting thoracic scoliosis, if our preliminary studies are verified by others.


Acclimation of barley to changes in light intensity: chlorophyll organization.
Barley seedlings (Hordeum vulgare L. cv. Boone) were grown at 20°C with a 16h/8h light/dark cycle of either high (H) intensity (550 μmole m(-2) s(-1)) or low (L) intensity (55 μmole m(-2) s(-1)) white light. Plants were transferred from high to low (H → L) or low to high (L → H) light intensity at various times from 4 to 8 d after leaf emergence from the soil. Primary leaves were harvested at the beginning of the photoperiod and a 3 cm apical segment removed for analysis. H control plants had greater chlorophyll (Chl) per leaf area and higher Chl a/b ratios than L controls. Analysis of Chl-protein complexes revealed that H and L plants had the same percentage of total Chl (62-65%) associated with Photosystem II (PS II), but that the organization of Chl within PS II was different. H plants contained lower levels of light-harvesting complex (LHC-II) and higher levels of the PS II complex CPa compared with L plants. Leaf Chl content and Chl organization within PS II were sensitive to changes in light intensity. In H → L plants, leaf Chl content decreased, Chl a/b ratio decreased, and a redistribution of Chl from CPa to LHC-II occurred during acclimation to low light. Acclimation of L → H plants to high light involved an increase in leaf Chl content, an increase in Chl a/b ratio, and a decrease in LHC-II. In contrast, the level of photosystem I related Chl-protein complexes (CP1 + CP1a) was similar in all light treatments. The light acclimation process occurred slowly over a period of 6 to 8 d in H → L and L → H plants.


Transcriptional regulation by histone modifications: towards a theory of chromatin re-organization during stem cell differentiation.
Chromatin-related mechanisms, as e.g. histone modifications, are known to be involved in regulatory switches within the transcriptome. Only recently, mathematical models of these mechanisms have been established. So far they have not been applied to genome-wide data. We here introduce a mathematical model of transcriptional regulation by histone modifications and apply it to data of trimethylation of histone 3 at lysine 4 (H3K4me3) and 27 (H3K27me3) in mouse pluripotent and lineage-committed cells. The model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions of the complexes with DNA and modified histones create a regulatory switch of transcriptional activity. The regulatory states of the switch depend on the activity of histone (de-) methylases, the strength of complex-DNA-binding and the number of nucleosomes capable of cooperatively contributing to complex-binding. Our model explains experimentally measured length distributions of modified chromatin regions. It suggests (i) that high CpG-density facilitates recruitment of the modifying complexes in embryonic stem cells and (ii) that re-organization of extended chromatin regions during lineage specification into neuronal progenitor cells requires targeted de-modification. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification.


Mesoporous α-Fe2O3 thin films synthesized via the sol-gel process for light-driven water oxidation.
This work reports a facile and cost-effective method for synthesizing photoactive α-Fe(2)O(3) films as well as their performances when used as photoanodes for water oxidation. Transparent α-Fe(2)O(3) mesoporous films were fabricated by template-directed sol-gel chemistry coupled with the dip-coating approach, followed by annealing at various temperatures from 350 °C to 750 °C in air. α-Fe(2)O(3) films were characterized by X-ray diffraction, XPS, FE-SEM and electrochemical measurements. The photoelectrochemical performance of α-Fe(2)O(3) photoanodes was characterized and optimized through the deposition of Co-based co-catalysts via different methods (impregnation, electro-deposition and photo-electro-deposition). Interestingly, the resulting hematite films heat-treated at relatively low temperature (500 °C), and therefore devoid of any extrinsic dopant, achieve light-driven water oxidation under near-to-neutral (pH = 8) aqueous conditions after decoration with a Co catalyst. The onset potential is 0.75 V vs. the reversible hydrogen electrode (RHE), thus corresponding to 450 mV light-induced underpotential, although modest photocurrent density values (40 μA cm(-2)) are obtained below 1.23 V vs. RHE. These new materials with a very large interfacial area in contact with the electrolyte and allowing for a high loading of water oxidation catalysts open new avenues for the optimization of photo-electrochemical water splitting.


[Intensified insulin therapy. References for general practice for increased control].
Today, intensified conventional insulin therapy (ICT) is the standard treatment for type 1 diabetes, but patients with type 2 diabetes younger than 70 also profit it. Within an international framework too, the DCCT study has confirmed the usefulness of intensified insulin therapy. Factors that have a decisive influence on the success of such treatment are the choice of a suitable insulin, its dose, site of injection, and prandial adaptation. The various possibilities of carrying out ICT are discussed.


Lacrimal Gland Involvement in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome.
To describe the involvement of the lacrimal gland (LG) in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). Observational, cross-sectional study. Twenty-one patients with BPES (10 female, 11 male) aged on average 15 years (range, 2-39 years), from 3 Brazilian medical centers and 1 Portuguese medical center. Patients had their ocular surface evaluated with slit-lamp biomicroscopy, and tear production quantified with the Schirmer test I. The LG volumes were measured on computed tomography (CT) scans in the BPES sample and in a group of age-matched subjects imaged for nonorbital diseases. Sixteen patients were screened for mutations in the FOXL2 gene. Lacrimal meniscus height, Schirmer test I, presence of superficial punctate keratopathy (SPK), LG volume, and molecular analysis of the FOXL2 gene. Absence of LG was detected bilaterally in 9 patients (42.8%) and unilaterally in 2 patients (9.5%). When considering only patients with measurable LG, the median volume was 0.22 cm3 in the right eye (range, 0.06-0.36 cm3) and 0.24 cm3 in the left eye (range, 0.08-0.34 cm3). These values were significantly lower than those for the age-matched controls (median = 0.54 right eye and 0.53 left eye; P < 0.05). There was a significant association between deficiency of tear production and LG volume reduction and agenesis. Molecular analysis of the FOXL2 gene revealed the presence of 8 distinct mutations, 4 of them novel ones. A significant reduction of LG size or agenesis was associated with mutations affecting protein size (due to underlying changes in the stop codon location) or the DNA-binding forkhead domain (Fisher exact test, P = 0.021). In 3 probands, the underlying genetic defect was not found. This is the first study reporting LG volumes in BPES, describing a significant number of patients with LG agenesis. The association between alacrima and BPES is not incidental, and a thorough evaluation of tear production is recommended especially if ptosis surgery is planned.


Antidepressant Exposure and Risk of Dementia in Older Adults with Major Depressive Disorder.
To identify whether duration of antidepressant use in depressed elderly veterans differed between those who later developed dementia and those who did not. Single-center, retrospective, observational, electronic chart review. Medical charts from a Veterans Affairs Mental Health Clinic. Veterans aged 65 and older with history of depression. Information on sociodemographic characteristics; duration of antidepressant, antipsychotic, and benzodiazepine therapy; diagnosis of dementia; and comorbid disease states was collected. Medication use since August 1, 1998 was recorded. Of 1,547 charts reviewed, 605 met inclusion criteria; 128 were excluded on the basis of psychiatric comorbidities. Of the remaining 477, 41 developed incident dementia. Thirty-seven of those were matched to individuals with depression without dementia according to age, cardiovascular disease, cerebrovascular disease, diabetes mellitus, and substance use. There were no differences between the groups with (n = 37) and without (n = 37) dementia with respect to baseline characteristics, antidepressant types, or benzodiazepine or antipsychotic use. Median duration of antidepressant use was 891 days in the group with dementia and 1,979 days in the group without (P = .03, W = -260, z = -2.13). Significantly fewer participants with dementia received antidepressant treatment for at least 5 years [n = 8 with dementia, n = 20 without dementia, P = .004, odds ratio = 0.235, 95% confidence interval = 0.085-0.647). Older veterans with depression who developed dementia were treated with antidepressants for a significantly shorter duration than matched veterans who did not develop dementia.


Reliability of sampling urine from disposable diapers in elderly incontinent women.
To assess the reliability for biochemical and microbiological analysis of urine collection from disposable diapers in elderly women with severe urinary incontinence. Cross-sectional comparison of two methods of collection. Urine was sampled from 52 women inpatients (aged 68-98 years) in a geriatric hospital ward by pressing a diaper which the patient had worn for 3 hours. Just after this collection, another sample was obtained by retrograde catheterization. Both samples were analyzed for sodium, potassium, chloride, proteins, urea, creatinine, calcium, and phosphate and for cell counts, the presence of bacteria, and bacteria culture. For all the biochemical parameters, the urinary concentrations obtained by the two methods were strongly and significantly correlated. The following differences (mean and range, in mmol/L) were found between the values obtained by the two methods: sodium: 6.05 (-26 to 27), potassium: (-16 to 14), chloride: -1.13 (-24 to 23), urea: 6.85 (-33 to 37), creatinine: 0.24 (-0.95 to 1.45), calcium: -0.22 (-1.27 to 1.70), and phosphate: 2.17 (-2.5 to 13.4). For diagnosis of urinary tract infection, agreement between the two methods was good (kappa = 0.84), and bacteriological agreement was obtained in 25 out of 28 cases (89%). However, for diagnosis of microscopic hematuria, agreement was poor (kappa = 0.50), probably due to the overestimation of the true urinary red cell count in the samples collected by catheterization. For routine microbiological and biochemical analysis, urine extraction from disposable diapers is a simple and reasonably reliable method of sampling urine from elderly women with severe incontinence.


Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy.
A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.


Carboxypeptidase B inhibitors reduce tissue factor-induced renal microthrombi in rats.
Procarboxypeptidase B (also known as thrombin-activatable fibrinolysis inhibitor) is a recently described plasma zymogen known to be activated by thrombin in plasma. Carboxy-terminal lysine residues from partially degraded fibrin are important for the binding and activation of plasminogen, and carboxypeptidase B, an active form of procarboxypeptidase B, has been shown to inhibit fibrinolysis by eliminating these residues. The present paper investigates the effects of carboxypeptidase B inhibitors, DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGPA) and potato-derived carboxypeptidase inhibitor (CPI), on tissue factor (TF)-induced microthrombosis in rats. Intravenous injection of MGPA (3 mg/kg and higher) or CPI (0.3 mg/kg and higher) after microthrombi formation dramatically attenuated TF-induced glomerular fibrin deposition with an increase in plasma levels of D-dimer. These results indicate that carboxypeptidase B inhibitors can enhance endogenous fibrinolysis and reduce thrombi in the TF-induced microthrombosis model after systemic administration even after thrombi formation.


Clinical substantiation of the sparing and less invasive implant prosthetics of the edentulous lower jaw method.
Proof of the effective implant prosthetics treatment of patients with the edentulous lower jaw by minimally invasive method. As a sample of clinical research, 68 senior patients (30 men and 38 women) were diagnosed with edentulous lower jaws. The methods of the study included estimating the implant retention by frequency-resonance analysis of Osstell ISQ, the degree of retention and stabilization of the tissue supported and implant-supported dentures (author's method: patent for invention No. 2640375 of 28.12.2017) and a sociologic questionnaire "Profile of the influence of dental health OHIP-14". For the first time strength indicators of the retention and stabilization degree of implant-retained mandibular overdentures with attachment to one and two implants were determined. A linear relationship was shown between the degree of fixation of the prosthesis and the change in the quality of life (a statistically significant correlation was p=0.022, r=0.52 in the first group and p=0.0015; r=0.75 in the second group). The implants stability during the year increased in the first group in 2.57±1.59%, and in the second group in 2.08±1.40%. After a year using implant-retained mandibular overdentures, the life quality level concerning dental health in patients from the first and second groups remained the same (there were no statistically significant differences, p1-2=0.8392). The performed survey of prosthetic treatment patients with the edentulous lower jaw showed the effect use of a sparing method of implantation prosthetics. The fixation quality achieved with a single support-retaining implant was sufficient to improve the functional and comfortable using of the lower jaw prosthesis. It was found that the stability of implants statistically did not significantly depend on the number of used implants (p>0.05).


Brain activity induced by implicit processing of others' pain and pleasure.
Studies indicate that both explicit and implicit processing of affectively charged stimuli may be reflected in specific behavioural markers and physiological signatures. Here, we investigated whether the pleasantness ratings of a neutral target were affected by the subliminal perception of a painful (a slap) or pleasant (a caress) touch delivered to others. In particular, we combined the continuous flash suppression technique with the affective misattribution procedure to explore subliminal processing of observed pain and pleasure in others. Results show that participants rated the neutral target as more or less likeable depending on whether they were subliminally primed with the pleasant or painful facial expression, respectively. The fMRI activity associated with painful and pleasant subliminal priming was mainly present in the anterior prefrontal cortex and the primary sensorimotor cortex, respectively. Thus, our study provides behavioural and neuro-physiological evidence that: (i) emotional reactivity toward positive or negative states of others can occur at an entirely subliminal level; (ii) specific neural substrates underpin reactivity to positive- and negative-valence of social emotions. Hum Brain Mapp 38:5562-5576, 2017. © 2017 Wiley Periodicals, Inc.


Radiotherapy and razoxane in advanced bile duct carcinomas.
Little is known about the radiation sensitivity of bile duct carcinomas. The current study was undertaken to prospectively assess the objective response rates in bile duct carcinomas treated with radiotherapy and razoxane. Twenty-three patients with advanced cancer of the biliary tree were irradiated together with the radiosensitizer razoxane at a dose of 125 mg twice daily by mouth. There were 16 females and 7 males, median age 68 years. They received a total tumor dose of 48 Gy (range 1.7-60) at the ICRU point with single fractions of 1.7 to 2 Gy. Among the 23 patients, 14 had measurable disease. Objective tumor responses were seen in 4/4 gallbladder carcinomas (1 CR, 3 PR), 4/5 extrahepatic cholangiocarcinomas (2 CR 2 PR), and 1/5 hepatobiliary cancers (1 PR), leading to an overall response rate of 64%. The tumors remained locally controlled in 12 out of 16 assessable patients (75%). On an intention-to-treat basis, all patients with different biliary cancer without distant metastases had a median-survival time of 10 months (range 1 to 48) from the start of the radiotherapy; the 1-year survival was 43%. No patient survived beyond 4 years. Tolerance to the treatment was fairly good. Nausea and vomiting of grade 1 and 2 (WHO) was noted in 61%, and reversible leukopenia of grade 3 and 4 in 9% of the cases. The rate of inherent complications was high. Combined radiotherapy and razoxane led to local response rates which are superior to data from the literature when radiotherapy alone is used. Obstacles to the treatment were complications of the disease and frequent metastasis.


[Analysis of surgical treatment of papillary thyroid carcinoma].
To present the treatment results and to analyze the causes of recurrence in patients with papillary thyroid carcinoma. A retrospective review of 600 patients with papillary thyroid carcinoma treated between 1994 and 1999 was conducted. The primary lesions were originated from the left lobe in 188 cases, the right lobe in 290 cases, the isthmus in 8 cases, and multicentric in 114 cases. From the 600 cases, 584 were well-differentiated and 16 poorly differentiated. TNM stage:385 cases of stage I, 37 cases of stage II, 17 cases of stage III, and 161 cases of stage IV. Three hundred and one patients was N1b stage. All patients received surgical treatment. Among them, 19 cases received radiotherapy, 71 received (131)I-therapy and one case received concomitant radiotherapy and (131)I-therapy. There were 94 recurrent cases. Twenty-seven cases died of recurrence, metastasis and other diseases. The overall 10-year survival rate was 93.2%. The overall 10 year survival rates of stage I, II, III, and IV patients were 99.1%, 94.7%, 93.8%, and 78.5%, respectively (P < 0.01). The 10-year survival rate of lower-age group (< 45 years) was 99.4% and higher-age group (≥ 45 years) 82.1% (P < 0.01). The 10-year survival rate of patients with trachea invasion was 66.5%, significantly lower than the 95.1% in patients without trachea invasion (P < 0.01). The 10-year survival rate of well-differentiated cases was 94.9%, significantly higher than the 38.9% in the poorly differentiated cases (P < 0.01). Multivariate analysis showed that the TNM stage, differentiation degree and the thorough going surgical operation were independent risk factors for the prognosis of papillary thyroid carcinoma. The TNM stage, differentiation degree and the thorough going surgical operation are independent risk factors for the prognosis of papillary thyroid carcinoma.


Does Islamic fasting affect cognitive functions in adolescents? A systematic review.
A considerable population of the Muslim community is made up of youngsters who observe fast during the month of Ramadan. There are other activities in Ramadan that the adolescents might be involved in, such as education in which one's proper cognitive activity is necessary. The current systematic review was planned to evaluate the relationship between Islamic fasting and cognitive activities. A number of studies have paid attention to the brain structure and scope of cognitive changes during fasting. Islamic fasting may affect cognitive activities such as spatial memory, visual memory and attention that play an important role in effective education. It is suggested to conduct a study with a larger sample size, using similar evaluation tools, targeting different cognitive tasks.


Representing disability and development in the global south.
I reflect on two aesthetics which are at play in the presentation of critical disability and development work in the global south. On the one hand, authors of critical texts commonly use very complex and abstruse language, which may make such texts relatively inaccessible to some disabled people in the global south. On the other hand, the ways in which development work in the south is portrayed sometimes emphasises methods of engagement which may seen to be infantilising. Drawing on my own experience in such engagement activities, I suggest that it is important to understand, and to subvert, dominant forms of representation.


Evaluation of a programme to train Russian émigré nurses.
This project evaluates a curriculum model designed to specifically help Russian émigré nurses overcome major barriers to employment in the United States of America. Training cycles included: vocational English, basic nursing skills, socialization theory, transcultural care theory, clinical preceptorships, job search workshops and NCLEX-RN preparation. Specific learning objectives and outcome criteria were developed, evaluated and adapted for subsequent training cycles based on pilot programme testing.


Mood and general behavior of patients with severe dementia during one year of supervised, individualized planned care and systematic clinical supervision. Comparison with a similar control group.
The aim of this study was to evaluate the effects of one year of systematic clinical supervision, and supervised individually planned care on the mood and general behavior of patients with dementia in relation to their cognitive function and level of confusion. The intervention was carried out in a ward devoted to the care of patients with severe dementia (EW), with a similar ward (CW) where no changes were made serving as a control. Each ward housed 11 patients, of whom 7 patients in each ward survived throughout the study time. Assessment of the patients' mood, general behavior, cognitive functions (MMSE), orientation and confusion (OBS) was made at baseline, and after 6 and 12 months of intervention. Significant deteriorations for the patients in CW were seen during the study period as regards the factor strength, functional performance and orientation in the ward, and speech performance and psychomotor slowing. For the patients in the EW, deterioration was seen only in the factor accessibility, and improvement was seen in the factor sensitivity and euphoria. The differences indicated that the development in the two wards went in opposite directions to the benefit of the patients in the EW. Because of the small sample size, the findings are more the result of a pilot trial, rather than generalizable. The intervention, however, seemed to have a positive effect on the secondary symptoms of the disease.


Studies on the L-2-hydroxy-acid oxidase 2 catalyzed metabolism of S-mandelic acid and its analogues.
Mandelic acid (MA) is generally used as a biomarker of the exposure of styrene, which is classified as a class of hazardous environmental pollutants, and also used as an important chiral intermediate in pharmaceutical industry. The previous studies have found the excretion of phenylglyoxylic acid (PGA) in human and rat, a metabolite of MA, was mainly from S-MA rather than R-MA. The metabolic mechanism, however, is not clear. In order to explore the possible metabolic mechanism, the enzyme types involved in the stereoselectivity metabolism of MA were firstly studied, and then human and rat long-chain 2-hydroxy-acid oxidase 2 (HAO2) were recombinantly expressed to study the metabolic profiles of S-MA and its analogues. The results indicated that HAO2 might catalyze the stereoselectivity metabolism of S-MA in rats. Human HAO2 (hHAO2) and rat HAO2 (rHAO2) isozymes β1 and β2 were successfully cloned and expressed with high purity and good enzyme activities. The enzyme kinetic profiles of these enzymes were different for S-MA and analogues. The order of catalytic efficiency for hHAO2 and rHAO2, however, was reverse. It might be relevance to the difference in active amino acid residues and loop 4 in human and rat L-2-hydroxy acid oxidase isozyme B crystal structures.


Employment status of spinal cord injured patients 3 years after injury.
This study examined the influence of selected medical, demographic, and epidemiologic variables on the spinal cord injured patient's return to gainful employment 3 years postinjury. Discriminant analysis was the statistical method selected as most appropriate for this study. Utilizing the best combination of predictor variables, the proportion of variance in "working" and "not working" groups explained by discriminant function was 65%. These variables included sex, race, marital status, extent of lesion, preinjury employment history, high Barthel score, incidence of urinary tract infection, and completion of any business or trade school courses. Patients who returned to work were more likely to be (1) young, (2) white, (3) female, and (4) working at the time of injury, and (5) were more likely to have a high Barthel score. Among a validation sample of 34 patients, 71% were correctly classified as employed or unemployed 3 years after injury. While other determinants of vocational rehabilitation undoubtedly exist, individual potential of a given spinal cord injured patient can probably be assessed by means of a relatively small set of predictor variables.


Determination of PAHs in dust from Shanghai by optimized SFE and GC/MS.
EPA 16 priority polycyclic aromatic hydrocarbons (PAHs) were extracted from dust by supercritical fluid extraction (SFE). Parameters (pressure, temperature and time) affecting the collection efficiencies of PAHs were assessed according to the extraction efficiency, and 30 MPa, 80 degrees C and 30 min dynamic extraction time were confirmed to be the best and simplest conditions of SFE to extract 16 priority PAHs from dust. The characterization of the extracts was carried out by gas chromatography with mass detector in selective ion mode (GC/MS/SIM). Ultrasonic extraction (USE) was used as a comparison with SFE. The results showed that the SFE method has a better efficiency than USE for the extraction of PAHs in dust. With the optimized conditions of SFE, the distribution of PAHs in dust samples in urban areas of Shanghai from Mar 10, 2005 to May 28, 2005 was investigated. The results demonstrated that traffic emission, especially from gasoline engines, was the main source of PAHs in dust of Shanghai.


Seed dispersal: the blind bomb maker.
A recent study shows that a desert shrub uses a 'mustard oil bomb' to regulate the behaviour of seed-predating rodents - transforming these predators into mutualistic seed dispersers.


Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates.
To explore the possibility that local injury to the endometrium in controlled ovarian hyperstimulation cycle improves the incidence of embryo implantation and to analyze the gene expression profile in the endometria of pregnant and nonpregnant patients in in vitro fertilization/embryo transfer (IVF-ET). Prospective study. A clinical assisted reproductive center of a university hospital. Women undergoing fresh IVF-ET cycles (n = 121), treated with a long protocol for controlled ovarian hyperstimulation, whose endometrium were diagnosed by B-ultrasound showing irregular echo. Local injury to the endometrium of 60 patients in controlled ovarian hyperstimulation cycle, who were randomly selected from a total of 121 patients. Seven endometrial biopsies samples from day 10 were analyzed by Affymetrix U133 plus 2.0 gene chip. Outcomes of IVF-ET and gene expression assayed by gene chip technology. Transfer of the same number of embryos (135 in the experimental and control patients, respectively) resulted in rates of implantation (33.33% vs. 17.78%), clinical pregnancy (48.33% vs. 27.86%), and ongoing or live births per ET (41.67% vs. 22.96%) that were higher in the experimental group compared with controls. Statistically significant differences of the expression level of 218 genes (41 up-regulated and 177 down-regulated) were detected in the endometrial biopsy samples from clinical pregnant patients and nonpregnant patients. The results suggested local injury to the endometrium during a COH cycle improved the rates of embryo implantation, clinical pregnancy and live birth in ART. We also demonstrated a statistically significant difference in the messenger RNA (mRNA) expression profiles in the endometrium of pregnant and nonpregnant patients. Further studies on the genes identified herein will assist in predicting implantation competence.


Identification of a repetitive element in the snail Biomphalaria glabrata: relationship to the reverse transcriptase-encoding sequence in LINE-1 transposons.
BamHI-digested Biomphalaria glabrata DNA contains a repetitive 2.0-kb fragment which is readily discernible by ethidium bromide staining. We present evidence that this repetitive element is related at both the nucleotide and amino acid levels to long interspersed nuclear element (LINE)-like transposons. Although comparable elements have been described in several invertebrates, this is the first report of a molluscan homologue. In common with LINE transposons, an open reading frame in the B. glabrata element shows significant homology to reverse transcriptase--a feature believed to allow the dissemination of these elements in the eukaryotic genome.


Treatment of acanthosis nigricans with etretinate (Tigason) in a patient with Lawrence-Seip syndrome (generalized lipodystrophy).
The major symptoms of Lawrence-Seip syndrome or generalized lipodystrophy consist of muscle hypertrophy, loss of subcutaneous fat, hyperlipaemia, diabetes mellitus and acanthosis nigricans. We have successfully treated acanthosis nigricans in a patient with Lawrence-Seip syndrome.


Structural Analysis of the Arabidopsis AL2-PAL and PRC1 Complex Provides Mechanistic Insight into Active-to-Repressive Chromatin State Switch.
Polycomb group proteins play essential roles in transcriptional gene repression during both animal and plant development. Polycomb repression complex 1 (PRC1) is one of the key functional modules in polycomb group silencing. It acts as both a reader of H3K27me3 (histone H3 lysine 27 trimethylation) and a writer of H2Aub1 (histone H2A monoubiquitination) in establishing stable repression chromatin state. Intriguingly, a recent study showed that Arabidopsis PRC1 contains the H3K4me3-binding proteins of the ALFIN-like (AL) family, pointing to a chromatin state switch from active to repressive transcription of embryonic genes required for vegetative plant development. However, molecular and structural basis of AL-PRC1 complexes are lacking, which harmed insightful mechanistic understanding of AL-PRC1 complex function. In the present study, we report the crystal structures of the PAL domain (DUF3594 domain) of AL2 and AL7 proteins as well as their mechanistic binding to the PRC1 ring-finger proteins (RING1 and BMI1). We found that the PAL domain exists as a homodimer and represents a novel protein fold. We further determined the crystal structures of the PAL domain of AL2 (AL2-PAL) in complex with AtRING1a and AtBMI1b, the two core components of Arabidopsis PRC1. Interestingly, two PAL-binding sites were found on AtRING1a. Each of them can bind AL but with different affinities and distinct structural bases. Based on our results, we propose a mechanistic model to understand how AL proteins target PRC1 to active chromatin to undergo the transition from H3K4me3 to H2Aub1/H3K27me3 in establishing gene silencing.


Disinfection byproduct regulatory compliance surrogates and bromide-associated risk.
Natural and anthropogenic factors can alter bromide concentrations in drinking water sources. Increasing source water bromide concentrations increases the formation and alters the speciation of disinfection byproducts (DBPs) formed during drinking water treatment. Brominated DBPs are more toxic than their chlorinated analogs, and thus have a greater impact on human health. However, DBPs are regulated based on the mass sum of DBPs within a given class (e.g., trihalomethanes and haloacetic acids), not based on species-specific risk or extent of bromine incorporation. The regulated surrogate measures are intended to protect against not only the species they directly represent, but also against unregulated DBPs that are not routinely measured. Surrogates that do not incorporate effects of increasing bromide may not adequately capture human health risk associated with drinking water when source water bromide is elevated. The present study analyzes trihalomethanes (THMs), measured as TTHM, with varying source water bromide concentrations, and assesses its correlation with brominated THM, TTHM risk and species-specific THM concentrations and associated risk. Alternative potential surrogates are evaluated to assess their ability to capture THM risk under different source water bromide concentration conditions. The results of the present study indicate that TTHM does not adequately capture risk of the regulated species when source water bromide concentrations are elevated, and thus would also likely be an inadequate surrogate for many unregulated brominated species. Alternative surrogate measures, including THM3 and the bromodichloromethane concentration, are more robust surrogates for species-specific THM risk at varying source water bromide concentrations.


Evaluation of the bond strength of a low-fusing porcelain to cast Ti-24Nb-4Zr-7.9Sn alloy.
The purpose of this study was to compare the bonding characteristics of titanium porcelain Duceratin bonded to Ti-24Nb-4Zr-7.9Sn (TNZS) alloy and commercial pure titanium (cp Ti). The bond strengths between porcelain and TNZS were tested by a three-point flexural device. The same tests for the cp Ti were used as for the control. Coefficient of thermal expansion (CTE) of TNZS was evaluated with a push-rod dilatometer. Interfacial characterization was carried out by X-ray energy-dispersive spectrometry (EDS) analysis operating in line scan mode. Additionally, microstructure characterizations of TNZS and cp Ti after debonding fracture were analyzed by scanning electron microscope (SEM) and EDS. The porcelain bond strength of TNZS alloy was 31.51MPa, showing a significant increase relatively to that of cp Ti (23.89 MPa) (P<0.05). Mean CTE values of TNZS alloy was 9.51×10(-6)/°C exceeding the porcelain by 0.81×10(-6)/°C, attesting to a better mechanical performance. Interfacial characterization showed the mutual diffusion of Ti, Si, O and Sn along the TNZS-ceramic interface. Both SEM and EDS results revealed that fracture modes of TNZS specimens exhibited a mixed mode of cohesive and adhesive failures. The results demonstrated that TNZS could be a good alternative for the metal-ceramic restoration in the future.


Isolation and characterization of 14 microsatellite loci for the Chevrier's field mouse (Apodemus chevrieri).
We describe the isolation and characterization of 14 microsatellite loci in the Chevrier's field mouse from genomic DNA-enriched libraries. The 14 loci were highly polymorphic with numbers of alleles per locus in 24 individuals ranging from three to 13, observed heterozygosity from 0.381 to 0.867 and expected heterozygosity from 0.448 to 0.931. All loci followed Hardy-Weinberg expectations except for CFM3, CFM10 and CFM12 loci. No significant linkage association was found among all these loci. The 14 polymorphic microsatellite loci will be useful in studying phylogeography and population genetics of the Chevrier's field mouse.


[The growth, chemical composition and strength properties of the long tubular bones in the skeleton of white rats under the influence of low-energy laser radiation].
Influence of He-Ne laser on skeleton bones of rats was studied. Morphometrical, histological, methods were applied; the chemical content was established. The conclusion is made that laser can be used for the optimisation of growth, mineralization and stability of skeleton bones.


First principles multielectron mixed quantum/classical simulations in the condensed phase. I. An efficient Fourier-grid method for solving the many-electron problem.
We introduce an efficient multielectron first-principles based electronic structure method, the two-electron Fourier-grid (2EFG) approach, that is particularly suited for use in mixed quantum/classical simulations of condensed-phase systems. The 2EFG method directly solves for the six-dimensional wave function of a two-electron Hamiltonian in a Fourier-grid representation such that the effects of electron correlation and exchange are treated exactly for both the ground and excited states. Due to the simplicity of a Fourier-grid representation, the 2EFG is readily parallelizable and we discuss its computational implementation in a distributed-memory parallel environment. We show our method is highly efficient, being able to find two-electron wave functions in approximately 20 s on a modern desktop computer for a calculation this is equivalent to full configuration interaction (FCI) in a basis of 17 million Slater determinants. We benchmark the accuracy of the 2EFG by applying it to two electronic structure test problems: the harmonium atom and the sodium dimer. We find that even with a modest grid basis size, our method converges to the analytically exact solutions of harmonium in both the weakly and strongly correlated electron regimes. Our method also reproduces the low-lying potential energy curves of the sodium dimer to a similar level of accuracy as a valence CI calculation, thus demonstrating its applicability to molecular systems. In the following paper [W. J. Glover, R. E. Larsen, and B. J. Schwartz, J. Chem. Phys. 132, 144102 (2010)], we use the 2EFG method to explore the nature of the electronic states that comprise the charge-transfer-to-solvent absorption band of sodium anions in liquid tetrahydrofuran.


From cards to computers: the National Library of Medicine and the transmission of medical knowledge.
The National Library of Medicine (NLM) is the world's largest medical Library. Its collections total some 6 million items and NLM also sponsors a variety of key databases in the medical field. This article traces the history and the strategies of the Library from the origins until today.


Prediction of community-acquired pneumonia using artificial neural networks.
Artificial neural networks (ANN) have been used in the prediction of several medical conditions but have not been previously used to predict pneumonia. The authors used ANN to predict the presence or absence of pneumonia among patients presenting to the emergency department with acute respiratory complaints and compared the results with those obtained using logistic regression modeling. Feed-forward back-propagation ANN were trained on sociodemographic, symptom, sign, comorbidity, and radiographic outcome data among 1,044 patients from the University of Illinois (the training cohort) and were applied to 116 patients from the University of Nebraska (the testing cohort). ANN trained using different strategies were compared to each other and to main-effects logistic regression. Calibration accuracy was measured as mean square error and discrimination accuracy as the area under a receiver operating characteristic (ROC) curve. A 1 hidden-layer ANN trained using oversampling of pneumonia cases had an ROC area in the training cohort of 0.895, which was greater than the area of 0.840 for logistic regression (P = 0.026). This ANN had an ROC area in the testing cohort of 0.872, not significantly different from its area in the training cohort (P = 0.597). Operating at a threshold of 0.25, the ANN would have detected 94% to 95% of patients with pneumonia in the 2 cohorts while correctly excluding 39% to 50% of patients with other conditions. ANN trained using other strategies discriminated equally in the 2 cohorts but no better than did logistic regression. Among adults presenting with acute respiratory illness, ANN accurately discriminated patients with and without pneumonia and, under some circumstances, improved on the accuracy of logistic regression.


Gaze patterns in laparoscopic surgery.
By understanding surgeons' patterns of gaze, and what visual information is being obtained during a procedure, one can improve the operation via new techniques or instrumentation. Part of a larger project on Remote Manipulation in Endoscopic Surgery, we analyzed eye patterns of surgeons from videotape annotation. Three categories of eye patterns were defined: 1) eyes on (gaze on monitor); 2) eyes down (gaze on external operative space); 3) eyes off (gaze away from monitor/hands). In the context of hierarchical decomposition of procedures we compared eye patterns and sequential dependencies (gaze as a function of previous gaze) by procedure, surgical steps and tasks. Timelines showed transitions in eye patterns during the procedure. We determined what visual information is available and what visual information is needed by the surgeons. By comparing these, we suggest technology that can provide these needs.


Ligand-selective targeting of the glucocorticoid receptor to nuclear subdomains is associated with decreased receptor mobility.
The association between nuclear distribution and mobility of the human glucocorticoid receptor was examined in living COS-1 cells using yellow fluorescent protein- and cyan fluorescent protein-tagged receptors. Quantitation of the nuclear distribution induced by an array of glucocorticoid ligands revealed a continuum from a random (cortisone) to a nonrandom (triamcinolone acetonide) receptor distribution. Structure-function analysis revealed that the 9-fluoro and 17-hydroxy groups on the steroid significantly impact nuclear receptor distribution. Using time-lapse microscopy, the triamcinolone acetonide-induced receptor distribution did not change significantly over a period of 15 sec. However, using fluorescence recovery after photobleaching, the individual receptors moved at a much faster rate, indicating rapid exchange of receptors on immobile nuclear subdomains. Receptor mobilities for 13 different steroids, measured by fluorescence recovery after photobleaching, appeared to correlate with receptor distribution. Ligands that induced a nonrandom distribution induced slower receptor mobility and vice versa. Finally, application of 2-photon confocal microscopy revealed differences in receptor mobility between nuclear subdomains. Areas of high receptor concentration showed slower mobility than areas of low receptor concentration. Thus, glucocorticoid receptors can be targeted (depending on the ligand) to relatively immobile nuclear subdomains. The transient association of receptor with these domains decreases the mobility of the receptor.


[Muscular compliance of the auditory tube].
The simultaneous electromyographical assessment of innervation patterns of the mylohyoid and the tensor veli palatini muscle is introduced as a new technique for the examination of the auditory tube function. Clinical studies were performed on 30 healthy volunteers and 50 patients suffering from chronic tubotympanic mucositis and cholesteatoma. Concentric needle electrodes were advanced into the tensor veli palatini muscle through the palate. The mylohyoid muscle was examined using surface electrodes. Innervation patterns of the tensor veli palatini muscle in volunteers were limited to the time interval of the mylohyoid innervation pattern only, i.e., the oral and pharyngeal phases of swallowing. In 14 of the chronic otitis patients these tensor muscle innervation patterns were found outside this interval. This observation provides a new pathophysiological explanation for the clinical concept of a relative closing failure of the auditory tube. These results emphasize the significance of coordination in muscular compliance of the tube.


Study of circulating antibodies against CD25 and FOXP3 in breast cancer.
Our recent work suggests that circulating levels of anti-CD25 and anti-FOXP3 antibodies were significantly increased in patients with either lung cancer or esophageal cancer. To confirm if these two autoantibodies are specific for certain types of malignant tumors, the present work was thus undertaken to examine an alteration of anti-CD25 and anti-FOXP3 IgG levels in breast cancer. A total of 152 patients with breast cancer and 112 control subjects were recruited in this study. The levels of circulating anti-CD25 and anti-FOXP3 IgG antibodies were tested using an in-house enzyme-linked immunosorbent assay (ELISA). Student's t test showed no significant differences in the levels of either anti-CD25 IgG or anti-FOXP3 IgG between patients with breast cancer and control subjects, although patients at stage I had increased levels of anti-CD25 IgG compared with control subjects (t = 2.11, P = 0.037); there was no significant association of the anti-FOXP3 IgG levels with stages of breast cancer. In conclusion, circulating IgG autoantibody to CD25 instead of FOXP3 may be a potential biomarker for early diagnosis of breast cancer but further investigation remains needed to replicate this initial finding.


Ewing's sarcoma of bone--a study of 71 cases by fine needle aspiration cytology.
Fine needle aspiration cytology (FNAC) plays immense diagnostic role in Ewing's sarcoma of bone. As clinically and sometimes radiologically Ewing's sarcoma mimics osteomyelitis of bone, FNAC is of great help to distinguish these 2 lesions and can avoid unnecessary incisional biopsies in most of the cases. At present limb salvage therapy is replaced by chemotherapy and radiotherapy. Moreover most of the patients present with gross soft tissue involvement where exact categorisation of malignant bone tumour is not possible by radiological means. FNAC is of great benefit to the clinicians and the patients as it provides a quick and accurate report and surgical interventions can be avoided in most of the cases. This paper highlights the cytological appearance of Ewing's sarcoma of bone in 71 cases. A conclusive diagnosis can be made with the help of special stains and cell block study. The diagnostic accuracy was 100% without any complication.


CDK inhibitors induce mitochondria-mediated apoptosis through the activation of polyamine catabolic pathway in LNCaP, DU145 and PC3 prostate cancer cells.
Androgen signaling is critical in prostate cancer development and progression. The co-existence of hormone responsive and irresponsive cells due to functional androgen receptor (AR) in prostate gland is the major obstacle in prostate cancer therapy models. Targeting aberrant cell cycle by novel cell cycle blocking agents is a promising strategy to treat various types of malignancies. Purvalanol and roscovitine are cyclin dependent kinase (CDK) inhibitors able to activate apoptotic cell death by inducing cell cycle arrest at G1/S and G2/M phases in cancer cells. Polyamines are unique cationic amine derivatives involved in the regulation of cell proliferation. Although the elevated intracellular level of polyamines (putrescine, spermidine and spermine) is typical for prostate gland, abnormal regulation of polyamine metabolism might result in rapid cell proliferation and, thus in prostate cancer progression. Therefore, treatment with drug-induced depletion of intracellular polyamine levels through the activated polyamine catabolism is critical to achieve successful strategies for prostate cancer. In this study we aimed to investigate the apoptotic efficiency of CDK inhibitors in three prostate cancer cell lines (LNCaP, DU145 and PC3), showing different AR expression profile. We found that both purvalanol and roscovitine were able to induce apoptosis at moderate cytotoxic concentrations by decreasing mitochondria membrane potential. The apoptotic effect of both CDK inhibitors was due to activation of caspases by modulating Bcl-2 family members. The efficiency of drugs was quite similar on the three prostate cell lines used in this study. However, DU145 cells were found the least sensitive against CDK inhibitors while purvalanol was more potent than roscovitine. Similarly to classical chemotherapeutic agents, both drugs could up-regulate polyamine catabolic enzymes (SSAT, SMO and PAO) in cell type dependent manner. Transient silencing of SSAT and/or inhibition of PAO/ SMO with MDL72527 prevented CDK inhibitors- induced apoptotic cell death in DU145 and PC3 cells. Although roscovitine was less effective in DU145 cells, pre-treatment with α-difluoromethylornithine (DFMO), an inhibitor of ODC, enhanced the roscovitine-induced apoptotic cell death through the cleavage of caspase-9 and caspase-3. Therefore, we conclude that polyamine catabolism might have essential role in the cellular responses against CDK inhibitors in different androgen-responsive or irresponsive prostate cancer cells.


Temperature and neuronal circuit function: compensation, tuning and tolerance.
Temperature has widespread and diverse effects on different subcellular components of neuronal circuits making it difficult to predict precisely the overall influence on output. Increases in temperature generally increase the output rate in either an exponential or a linear manner. Circuits with a slow output tend to respond exponentially with relatively high Q(10)s, whereas those with faster outputs tend to respond in a linear fashion with relatively low temperature coefficients. Different attributes of the circuit output can be compensated by virtue of opposing processes with similar temperature coefficients. At the extremes of the temperature range, differences in the temperature coefficients of circuit mechanisms cannot be compensated and the circuit fails, often with a reversible loss of ion homeostasis. Prior experience of temperature extremes activates conserved processes of phenotypic plasticity that tune neuronal circuits to be better able to withstand the effects of temperature and to recover more rapidly from failure.


An objective assessment of the value of exercise training to patients with chronic obstructive airways disease.
The value of a programme of graded exercise training was assessed in ten subjects with chronic obstructive airways disease. Assessments were made at two-weekly intervals during three twelve-week periods: before, during and after a period of training. During the training the subjects were able to walk significantly further in a 12 minute walking test. There was also a small but significant increase in the forced expiratory volume in one second and the difference between the values of total lung capacity estimated by body plethysmography and those estimated by helium dilution was significantly smaller. The transfer factor for carbon monoxide increased and was significantly greater in the period after stopping the training. The difference between alveolar and arterial oxygen tensions at rest was smaller during the training period. The changes in the results of the 12 minute walking test, transfer factor and the oxygen tension difference were maintained in the period after stopping the training. Despite the improvements in some of the indices of respiratory function there were no improvements in any of the indices of cardiorespiratory fitness which may be because the subjects were incapable of undertaking sufficiently intense training. It is concluded that training is of some benefit to patients with chronic obstructive airways disease but that the benefit may be greater in patients who are less incapacitated and who are able to undertake a more strenuous training programme.


Coccygectomy for severe refractory sacrococcygeal joint pain.
Severe refractory coccydynia occasionally requires coccygectomy. Methods involved a retrospective chart review plus telephone follow-up of 15 patients who had coccygectomy. Pain was assessed by the numerical rating scale and function by Oswestry Low Back Disability Score. There were 13 (87%) patients (four men, nine women) available for follow-up at a mean of 43 months (range 19-74 months). Mean age was 45 years (range 24-72 years). All patients had coccygeal pain arising from the sacrococcygeal joint, but there were other lumbar disorders in 10 patients. There were two complications. The numerical rating scale improved from 7.3 to 3.6 (p < 0.001), and the Oswestry Low Back Disability Score improved from 55 to 36 (p < 0.001). Twelve patients would have the same surgery for the same result. Coccygectomy provides statistically and clinically significant improvement in patients with severe refractory sacrococcygeal joint pain. Many patients have other lumbar spine pathology.


Is mucosal healing more common than clinical remission in ulcerative colitis? - Is it the truth or only a myth coming from the studies?
The most important goals of the recent therapies of ulcerative colitis (UC) are to induce and maintain clinical remission and to achieve mucosal healing (MH). Rate of endoscopic remission has been shown to be higher than that of clinical remission in large trials like ULTRA and PURSUIT. The aim of our study was to evaluate the correlation between clinical and endoscopic disease activities of UC defined by activity scores. Clinical and endoscopic activities were evaluated in 100 consecutive UC patients. Clinical activities were defined by two activity indices: the Rachmilewitz Activity Index (CAI) and the partial Mayo score. Colonoscopies and patient enrollments were performed by two experienced gastroenterologists and endoscopists. They graded the findings both according to the endoscopic part of the Rachmilewitz Endoscopic Activity Index (EI) and the Mayo endoscopic subscore. MH was defined as Mayo endoscopic subscore and EI of 0. Histological activity was scored by Riley score. Clinical and endoscopic activities showed strong correlations using both scoring systems (p = 0.0029 and p = 0.0001). Endoscopic disease activity also correlated with the histological activity (p ≥ 0.001). Significant correlation was shown between the clinical activity and MH (p = 0.0012 and p ≥ 0.001). No association was showed with the extension of the disease and clinical or endoscopic activity. Assessment of MH is very important for guiding therapy and for evaluation of remission in patients with UC. Our result showed good correlation between the clinical, endoscopic, and histological activities of UC focusing on the importance of evaluating the endoscopic activity of the patients.


Genome Engineering Using TALENs.
Genome engineering involves methods of genetic modification of cells at predefined genomic sites. Here, we used transcription activator-like effector nucleases (TALENs) for the site-directed mutagenesis in barley. Target gene-specific TALEN-encoding expression units were designed and delivered to totipotent cells of either cultivated embryogenic pollen or immature embryos. The analysis of resulting transgenic plants revealed that the described approach allows for the generation of site-specific, heritable mutations at reasonable efficiency.


Effect of salivary gland extract of Leishmania vector, Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis.
Salivary gland extracts (SGE) from Lutzomyia longipalpis potentate L. major infection by inducing a Th2 immune response. However, the effect of SGE on the effector phase of immune response is not known. Herein, we demonstrate that SGE inhibited neutrophil migration in ovalbumin (OVA)-induced peritonitis in immunized mice. SGE pretreatment of mice inhibited OVA-induced CD4+ and CD8+ T lymphocyte migration. The OVA-induced production of TNF-alpha, IL-1beta and leukotriene B4 (LTB4), neutrophil chemotactic mediators in this model, were inhibited by SGE. On the other hand, SGE enhanced production of IL-10 and IL-4. In naive mice, SGE also blocked LTB4-induced neutrophil migration, but not that induced fMLP. Moreover, co-incubation of LTB4 (but not fMLP, TNF-alpha and MIP-1alpha) with SGE inhibited the ability of LTB4 to induce neutrophil migration in vivo and in vitro. Altogether, the results suggest that SGE has anti-inflammatory properties that are associated with inhibition of TNF-alpha and LTB4 production and/or with the neutrophil chemotactic activity of LTB4. The effectiveness of SGE in inhibiting neutrophil migration and inflammatory mediators release in a Th1 immune inflammatory response model reinforces the need for isolation of the compounds responsible for these activities, which could be used as prototypes for the development new anti-inflammatory drugs.


Selecting against antibiotic-resistant pathogens: optimal treatments in the presence of commensal bacteria.
Using optimal control theory as the basic theoretical tool, we investigate the efficacy of different antibiotic treatment protocols in the most exacting of circumstances, described as follows. Viewing a continuous culture device as a proxy for a much more complex host organism, we first inoculate the device with a single bacterial species and deem this the 'commensal' bacterium of our host. We then force the commensal to compete for a single carbon source with a rapidly evolving and fitter 'pathogenic bacterium', the latter so-named because we wish to use a bacteriostatic antibiotic to drive the pathogen toward low population densities. Constructing a mathematical model to mimic the biology, we do so in such a way that the commensal would be eventually excluded by the pathogen if no antibiotic treatment were given to the host or if the antibiotic were over-deployed. Indeed, in our model, all fixed-dose antibiotic treatment regimens will lead to the eventual loss of the commensal from the host proxy. Despite the obvious gravity of the situation for the commensal bacterium, we show by example that it is possible to design drug deployment protocols that support the commensal and reduce the pathogen load. This may be achieved by appropriately fluctuating the concentration of drug in the environment; a result that is to be anticipated from the theory optimal control where bang-bang solutions may be interpreted as intermittent periods of either maximal and minimal drug deployment. While such 'antibiotic pulsing' is near-optimal for a wide range of treatment objectives, we also use this model to evaluate the efficacy of different antibiotic usage strategies to show that dynamically changing antimicrobial therapies may be effective in clearing a bacterial infection even when every 'static monotherapy' fails.


Relation to extrafusal fibre-type composition in muscle-spindle structure and location in the human masseter muscle.
Muscle-spindle density and size, in relation to extrafusal fibre-type, were examined in different portions of the masseter of six normal males by enzyme histochemistry. A direct relationship between spindle density, intrafusal fibre density and spindle size, and proportion of type I muscle fibres was found in the deep portion. Out of 410 muscle spindles in random samplings, 74 per cent were in the deep portion which is predominantly composed of type I fibres. Spindle density was three times greater than in the other portions, and spindles were commonly clustered, sometimes sharing capsule tissue. The deep masseter spindles were distinctive; they had the largest diameter and the most intrafusal fibres, the fibre density being four times greater than in other portions. Eleven per cent of the spindles, mainly in the deep portion, contained an unusually high number of intrafusal fibres (15 or more fibres). The findings imply that individual portions of the masseter have specialized functions. An especially powerful proprioceptive reflex mechanism is suggested for the deep portion. Thus, the human masseter may be part of an intricate, evolutionarily advanced, motor system also connected with speech.


Coherence-multiplexed, label-free biomolecular interaction analysis.
This Letter describes an interferometric technique based on the principle of coherence multiplexing for multichannel, label-free biosensing applications. Multiple biosensors can be interrogated simultaneously with a single spectral-domain, phase-sensitive interferometer by coding the individual sensograms in coherence-multiplexed channels. The experimental results demonstrate the multiplexed quantitative biomolecular interaction of antibodies binding to antigen-coated functionalized biosensor chip surfaces. The described technique also applies to a variety of other distributed and multiplexed sensing applications besides biosensing.


The mechanisms of action of plasma exchange.
The initial description of therapeutic plasma exchange (TPE) in an animal model was published almost 100 years ago. Since that time, this treatment has been applied to a wide variety of diseases but limited research has been published examining the mechanisms of action of TPE. The therapeutic effects of TPE could include the removal of pathological substances from the blood, such as monoclonal paraproteins and autoantibodies, as well as the replacement of deficient plasma components when plasma is used as a replacement fluid. Beyond these potential mechanisms, other possible mechanisms include possible alterations in lymphocyte proliferation and function that could sensitize these cells to immunosuppressant and chemotherapeutic agents and alterations in the immune system including changes in B and T cell numbers and activation, increased T suppressor function, and alteration in T-helper cell type 1/2 (Th1/Th2) ratio. Much remains unknown about the mechanisms of action of TPE, indicating a need for basic research into this therapy.


NK-cell-dependent acute xenograft rejection in the mouse heart-to-rat model.
Acute humoral xenograft rejection is characterized by widespread intravascular thrombosis with a significant NK-cell and macrophage infiltrate. Although in vitro and ex vivo data have shown that NK cells are capable of killing xenogeneic tissue, the precise role they play in vivo is still not certain. Consequently, there are few tested strategies for dealing with NK-cell-mediated rejection, should this prove to be a problem. One reason for this has been the lack of a relevant rodent model in which rejection by these cells can be easily studied. Prior to transplantation of mouse hearts, we depleted rat recipients of fibrinogen using a snake venom, ANCROD, from the Malayan pit viper. Graft survival was examined by manual palpation and the rejected hearts were examined by histology. Levels of circulating interferon gamma (IFN-gamma), used as a surrogate marker for NK-cell activation, were determined by an enzyme-linked immunosorbent assay. Depletion of fibrinogen to approximately 5% of normal allowed surgery without a significant increase in the technical failure rates and prolonged graft survival compared with that seen in unmanipulated rats. Rejected hearts showed no evidence of intravascular thrombosis but did show significant antibody and complement deposition. There was little T-cell infiltration and cyclosporin had no influence on survival. Instead, hearts were infiltrated with NK cells and macrophages and rejection was associated with significant IFN-gamma production. Depletion of NK cells with anti-asialo-GM-1 from ANCROD-treated recipients led to a further significant prolongation of graft survival. Inhibition of intravascular thrombosis by fibrinogen depletion, in the absence of any other manipulation, unmasks NK-cell-dependent acute xenograft rejection in the mouse-to-rat heart transplantation model. This relatively simple model is expected to be useful to investigate the mechanisms of NK-cell-mediated rejection and to provide insight into the types of graft manipulation that could modify this process.


Caenorhabditis elegans LET-767 is able to metabolize androgens and estrogens and likely shares common ancestor with human types 3 and 12 17beta-hydroxysteroid dehydrogenases.
Mutations that inactivate LET-767 are shown to affect growth, reproduction, and development in Caenorhabditis elegans. Sequence analysis indicates that LET-767 shares the highest homology with human types 3 and 12 17beta-hydroxysteroid dehydrogenases (17beta-HSD3 and 12). Using LET-767 transiently transfected into human embryonic kidney-293 cells, we have found that the enzyme catalyzes the transformation of both 4-androstenedione into testosterone and estrone into estradiol, similar to that of mouse 17beta-HSD12 but different from human and primate enzymes that catalyze the transformation of estrone into estradiol. Previously, we have shown that amino acid F234 in human 17beta-HSD12 is responsible for the selectivity of the enzyme toward estrogens. To assess whether this amino acid position 234 in LET-767 could play a role in androgen-estrogen selectivity, we have changed the methionine M234 in LET-767 into F. The results show that the M234F change causes the loss of the ability to transform androstenedione into testosterone, while conserving the ability to transform estrone into estradiol, thus confirming the role of amino acid position 234 in substrate selectivity. To further analyze the structure-function relationship of this enzyme, we have changed the three amino acids corresponding to lethal mutations in let-767 gene. The data show that these mutations strongly affect the ability of LET-767 to convert estrone in to estradiol and abolish its ability to transform androstenedione into testosterone. The high conservation of the active site and amino acids responsible for enzymatic activity and substrate selectivity strongly suggests that LET-767 shares a common ancestor with human 17beta-HSD3 and 12.


Survival analysis and microarray profiling identify Cd40 as a candidate for the Salmonella susceptibility locus, Ity5.
The outcome of infection with Salmonella Typhimurium in mouse models of human typhoid fever is dependent upon a coordinated complex immune response. A panel of recombinant congenic strains (RCS) derived from reciprocal backcross of A/J and C57BL/6J mice was screened for their susceptibility to Salmonella infection and two susceptibility loci, Ity4 (Immunity to Typhimurium locus 4) and Ity5, were identified. We validated Ity5 in a genetic environment free of the impact of Ity4 using a cross between A/J and 129S6. Using a time-series analysis of genome-wide transcription during infection, comparing A/J with AcB60 mice having a C57BL/6J-derived Ity5 interval, we have identified the differential expression of the positional candidate gene Cd40, Cd40-associated signaling pathways, and the differential expression of numerous genes expressed in neutrophils. CD40 is known to coordinate T cell-dependent B-cell responses and myeloid cell activation. In fact, CD40 signaling is altered in A/J mice as seen by impaired IgM upregulation during infection, decreased Ig class switching, neutropenia, reduced granulocyte recruitment in response to infection and inflammation, and decreased ERK1/2 activity. These results suggest that altered CD40 signaling and granulocyte recruitment in response to infection are responsible for the Ity5-associated Salmonella susceptibility of A/J mice.


Impulse and moment of impulse in the leg joints by impact from kicking.
In a previous paper we have given a theoretical analysis of the impulsive motion of the leg, modeled as a double pendulum. This analysis made it possible to estimate the impulsive reactions in the knee joint as a function of the measured initial and final velocities of the leg, when an impact was given to the lower leg, e.g., by means of a kick. This estimation was made under the assumption that no impulsive moments occur in the hip and the knee joints, i.e., that no muscles were stretched during the time of impact. In the present paper it is shown how such impulsive moments, should they occur, can be determined by means of an additional measurement, i.e., of the velocity of the ball after the impact. The results from a series of experiments are reported, showing that such impulsive moments in the joints occur in an appreciable number of the kicks, especially in the hip joint, indicating that muscles, acting on this joint, are prestressed during the impact.


Molecular cloning, characterization and expression of PmRsr1, a Ras-related gene from yeast form of Penicillium marneffei.
GTP-binding proteins such as Ras act as molecular switches in a large number of signal pathways. In this report, we isolated and characterized a novel Ras small monomeric GTPase Rsr1 gene, designated PmRsr1, from yeast-form Penicillium marneffei. The full-length PmRsr1 cDNA sequence is 1,866 bp in size, and contains an open reading frame of 642 bp encoding 213 amino acids. The predicted molecular mass of PmRsr1 is 24.41 kDa with an estimated theoretical isoelectric point of 9.21. The deduced amino acid sequence of PmRsr1 shows 87% identity with that of Aspergillus fumigatus and A. clavatus. Eight exons and seven introns are identified within the 2,102 bp PmRsr1 genomic DNA sequence of P. marneffei. The open reading frame was subcloned into the pcDNA6-myc-His B expression vector, and the recombinant plasmid was transfected into Vero cell line. The expressed fusion protein was analyzed by SDS-PAGE and western blotting. Differential expression of the PmRsr1 was demonstrated by real-time RT-PCR. The expression of PmRsr1 was the highest in the yeast phase comparing with that in the mycelia and conidia phases.


A simple method for long-term biliary access in large animals.
A simple method to obtain long-term access to the biliary tree in dogs and pigs is presented. In ten dogs and four pigs, a cholecystectomy was performed, the cystic duct isolated, and a catheter inserted into the cut end of the cystic duct. The catheter was connected to a subcutaneous infusion port, producing a closed, internal system to allow long-term access. The catheter placement was successful in three of the pigs and all of the dogs. Thirty-five cholangiograms were obtained in the 13 subjects by accessing the port with a 20 gauge Huber needle and injecting small amounts (4-10 mL) of contrast under fluoroscopic control. Cholangiograms were obtained up to four months after catheter placement without evidence for catheter failure or surgically induced changes in the biliary tree. This model provides a simple, reliable means to obtain serial cholangiograms in a research setting.


[A case of congenital Coxsackie B virus infection].
The paper describes a clinical case of congenital Coxsackie B virus infection in a girl aged 1 month and 15 days of life who has undergone a detailed postmortem examination.


Carbon nanotube-based ethanol sensors.
Sensors containing metal-carbon nanotube (CNT) hybrid materials as the active sensing layer were demonstrated for ethanol vapor detection at room temperature. The metal-CNT hybrid materials were synthesized by infiltrating single wall carbon nanotubes (SWNTs) with the transition metals Ti, Mn, Fe, Co, Ni, Pd or Pt. Each sensor was prepared by drop-casting dilute dispersions of a metal-CNT hybrid onto quartz substrate electrodes and the impedimetric responses to varying ethanol concentration were recorded. Upon exposure to ethanol vapor, the ac impedance (Z') of the sensors was found to decrease to different extents. The sensor containing pristine CNT material was virtually non-responsive at low ethanol concentrations (<50 ppm). In contrast, all metal-CNT hybrid sensors showed extremely high sensitivity to trace ethanol levels with 100-fold or more gains in sensitivity relative to the starting SWNT sensor. All hybrid sensors, with the exception of Ni filled CNT, exhibited significantly larger sensor responses to ethanol vapor up to 250 ppm compared to the starting SWNT sensor.


Evaluation of cII mutations in lung of male Big Blue mice exposed by inhalation to vanadium pentoxide for up to 8 weeks.
Chronic inhalation of vanadium pentoxide (V2O5) increases the incidence of alveolar/bronchiolar tumors in male and female B6C3F1 mice at 1, 2, or 4 mg/m(3). The genotoxicity of V2O5 has been extensively investigated in the literature with mixed results. In general, tests for gene mutations have been negative. Both positive and negative results were reported for clastogenicity in vitro with some reports suggesting aneugenic potential. In vivo, V2O5 was negative in the mouse micronucleus test (erythrocyte) and comet assay (lung). Previously, K-ras mutations have been detected in the lung tumors in mice exposed to V2O5. Recently, a short-term inhalation study in B6C3F1 mice reported slight induction of 8-oxodGuo DNA lesions in lungs. Because 8-oxodGuo DNA lesions can lead to gene mutations if not repaired or if misrepaired, we have used groups of transgenic Big Blue (BB) mice (B6C3F1) to test whether V2O5 has mutagenic potential in vivo in the tumor target tissue under the conditions of the bioassay. Groups of six male BB mice were exposed to particulate aerosols containing 0, 0.1, or 1 mg/m(3) (tumorigenic concentration) V2O5 for 4 or 8 weeks (6h/day, 5 days/week) and cII mutant frequencies (MFs) were evaluated in the right lungs. A significant increase in lung weight was noted in mice exposed to 1 mg/m(3) V2O5 (P ≤ 0.05) compared to sham control, confirming exposure to an inflammatory level of the test material. The mean MFs (× 10(-6)) of mice in the 4-week exposure groups were 30 (sham control), 39 (0.1 mg/m(3)), and 24 (1 mg/m(3)) while the corresponding values in the 8-week exposure groups were 29, 48, and 17, respectively. None of these cII MFs measured at any time point was significantly higher than the corresponding control MFs (P ≥ 0.1). Overall, these results suggest that mutagenicity is not likely to be an initial key event in the lung tumorigenicity of V2O5.


Exploring the roles of Mus81-Eme1/Mms4 at perturbed replication forks.
Cells of all living organisms have evolved complex mechanisms that serve to stabilise, repair and restart stalled, blocked and broken replication forks. The heterodimeric Mus81-Eme1/Mms4 structure-specific endonuclease appears to play an important role(s) in homologous recombination-mediated processing of such perturbed forks. This enzyme has been implicated in the cleavage of stalled and blocked replication forks to initiate recombination, as well as in the processing of recombination intermediates that result from repairing damaged forks. In this review we assess the biochemical and genetic evidence for the mitotic role of Mus81-Eme1/Mms4 at replication forks and in repairing post-replication DNA damage. Mus81 appears to act when replication is impeded by genotoxins or by impairment of the replication machinery, or when arrested replication forks are not adequately protected. We discuss how its action is regulated by the S-phase cell cycle checkpoint, depending on the nature of the stalled or damaged fork. We also present a new way in which Mus81 may limit crossing over during the repair of post-replication gaps, and explore Mus81's interplay with other components of the recombination machinery, including the RecQ helicases that also play important roles in processing replication and recombination intermediates.


Shotgun phage display of Lactobacillus casei BL23 against collagen and fibronectin.
Lactobacilli are normal constituents of the intestinal microbiota, and some strains show the capacity to bind to extracellular matrix proteins and components of the mucosal layer, which represents an adaptation to persist in this niche. A shotgun phage-display library of Lactobacillus casei BL23 was constructed and screened for peptides able to bind to fibronectin and collagen. Clones showing binding to these proteins were isolated, which encoded overlapping fragments of a putative transcriptional regulator (LCABL_29260), a hypothetical protein exclusively found in the L. casei/rhamnosus group (LCABL_01820), and a putative phage-related endolysin (LCABL_13470). The construction of different glutathione S-transferase (GST) fusions confirmed the binding activity and demonstrated that the three identified proteins could interact with fibronectin, fibrinogen, and collagen. The results illustrate the utility of phage display for the isolation of putative adhesins in lactobacilli. However, it remains to be determined whether the primary function of these proteins actually is adhesion to mucosal surfaces.


Measurement of blood pressure in children: recommendations and perceptions on cuff selection.
. To review some of the recent recommendations on blood pressure (BP) cuff selection, including those by the Task Force and its update, and to survey the perceptions on cuff selection among practitioners. The study was conducted in two parts. In the first, we selected three brands of commonly used infant, child/pediatric, small adult, adult, and large adult BP cuffs. From the median width of each, we derived the required upper arm length (UAL) for the cuff to cover three quarters or two thirds of the UAL, and with the help of a published normal UAL at various ages, we matched the derived UAL with the corresponding age at the 50th percentile. Similarly, we derived the midupper arm circumference (UAC) so that the available cuffs would cover 40% of the UAC, and by using the published normal UAC at various ages, we matched the derived UAC with the corresponding age at the 50th percentile. The second part of the study involved a survey by multiple choice questionnaire mailed to 400 hospital- and office-based pediatricians, residents, and nurses at the Children's Hospital of Michigan. Included in the survey were questions about the age at which practitioners would choose the cuffs described above; the minimum age they would consider using an adult cuff in a pediatric patient with an average height and weight; selecting a cuff using UAL as a criterion; selecting a large versus a small cuff when the appropriate cuff size is not available; and the Task Force definition of hypertension. Using three quarters of the UAL as a criterion, it seems that a large adult cuff should be appropriate for an average-size 6-year-old child and that using two thirds of UAL as a criterion, the cuff should be appropriate for an average-size 7- to 8-year-old child. Similarly, by using 40% of the mid-UAC as a criterion, an adult cuff would be of no use in an average pediatric patient at any age. Our survey revealed that 57% of practitioners would consider using a neonatal cuff for patients up to 1 month of age, 65% would use an infant cuff for those 1 year of age, 49% would use a child/pediatric cuff for those 5 years of age, and 84% would use a small adult cuff for those 10 years of age and older. Most (83%) of the practitioners would consider using an adult cuff in children 11 years of age and older. Practitioners are likely to use a smaller cuff than is appropriate by two thirds or three quarters of UAL criteria, and a larger cuff than is appropriate, particularly in older children, by 40% of UAC criteria. Using UAL as a criterion, a majority (59%) of practitioners use cuffs that cover two thirds of the distance between the axilla and the cubital fossa. Ninety-two percent of practitioners believe that a smaller cuff causes a moderate to significant increase in the BP reading, and 55% believe that a larger cuff causes a similar decrease in the BP reading. A significant number of practitioners (44%) did not know the Task Force definition of hypertension, including 42% of attendings, 44% of residents, and 50% of nurses. The Task Force and the Working Group recommendations on BP cuff selection need to be reviewed. A new multicenter study, using uniform criteria for cuff selection, may be necessary to establish the accuracy of the published nomogram on normal BP in children. More awareness is required on part of practitioners of the current recommendations on BP measurement and the definition of hypertension. Finally, the labeling of BP cuffs as infant, pediatric, small adult, adult, and large adult is misleading, and such designations should be eliminated. Cuff sizes should be standardized, indicate bladder size, and be uniformly color-coded for convenience.