Clinical applications of scanning electron microscopy and X-ray microanalysis in dermatology.
Scanning electron microscopy is frequently applied to dermatological problems, as is evident from a review of the recent literature. In this tutorial, preparation methods and new techniques allowing experimental studies on the integumentary system are emphasized. Quantitative analysis in the electron microscope by use of energy-dispersive X-ray microanalysis ( EDX ) has become an important accessory technique. EDX can, for instance, be used to study problems involving physiological changes induced in skin by agents causing contact reactions. Recently, it has been shown that treatment with DNCB, chromate and nickel causes changes in elemental distribution in guinea-pig skin. In addition, elemental uptake in the integumentary system and in pathological inclusions in skin can be analyzed.


Structure of extremely nanosized and confined In-O species in ordered porous materials.
Perturbed-angular correlation, x-ray absorption, and small-angle x-ray scattering spectroscopies were suitably combined to elucidate the local structure of highly diluted and dispersed InOx species confined in the porous of the ZSM5 zeolite. This novel approach allow us to determined the structure of extremely nanosized In-O species exchanged inside the 10-atom-ring channel of the zeolite, and to quantify the amount of In2O3 crystallites deposited onto the external zeolite surface.


[Respiratory system function in workers from the Mechanical Petrochemical Plant in Płock--influence of the workplace environment].
The aim of this study was to evaluate the influence of the work place environment on the function of the respiratory system. Study covered 211 male from Mechanical Plant of Plock Refinery (M.P. group 1) and the control group consisted of 53 male employed in Design Office (D.O. Group II). Group I was exposed to toxic substances (NO2, SO2, dust, manganese and iron oxides). Lung function tests were performed using laboratory "Compact-Lab" (JAEGER). The FVC, FEV1, FEV1%FVC, PEF, FEF50 were obtained from flow-volume curve and TGV, Rt measured using plethysmography method. Information concerning symptoms and cigarette smoking were obtained from questionnaire designed for this study. Mean values of respiratory indices were within normal range and did not differ between groups. The percentage of abnormal results was similar in groups. Air flow limitation (FEV1%FVC < 70%) was observed in 15.2% of total. Smokers have had significantly lower indies of air flow limitation but still within normal range. Symptoms (cough, expectoration, dyspnea) were equally frequent in M.P. and D.O. and significantly more frequent in smokers. In our study we did not find the influence of work place environment on the function of the respiratory system.


Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry.
There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS). Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax <4.5 m/s, N=550; group 2, 4.5 ≤ Vmax <5 m/s, N=279; and group 3, Vmax ≥5 m/s, N=246). Cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS-related events remained significant (hazard ratio, 1.39; 95% CI, 1.07-1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17-2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS-related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01-2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16-2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS-related events (interaction, P=0.88). In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS-related events. However, the cumulative 5-year incidence of the AS-related events remained very high even in asymptomatic patients with less greater Vmax.


[Pincoffs-Bard's syndrome in a 15-year old girl].
A case of primary stomach carcinoma (or Pincoff's-Bard syndrome) with extensive radiologic shadows on chest X-ray and clinical signs of respiratory failure has been presented. The case concerned a 15-year-old girl being diagnosed in several hospital because of pulmonary lesions. The diagnosis was made on a basis of the autopsy.


THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.
Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.


Nurse Staffing Norm in Iran Hospitals: What Features Should be Included for Success?
Designing and implementing a model for estimation and distribution of required nurse is one of strategies to prevent unequal distribution of nurses within and between hospitals. The purpose of this research was to determine required features for hospital nursing staff estimation model. We conducted a qualitative study using a Colaizzi analysis approach. We used semi-structure and in-depth interviews by purposive, quota, and snowball sampling of 32 participants (10 informed experts in area of policy making in human resources in Ministry of Health, 10 decisions making in employment and distribution of human resources in treatment and administrative chancellors of medical universities, and 12 process owners in hospitals). The data were analyzed using ATLAS.ti software version 6.0.15. The ten following sub-themes emerged from data analysis: Skill mix and task shifting, work measurement, legal support, stakeholder involvement in designing a model, considering the ward activity, considering type and extent of care patients required, model development by experts predominate in nursing process, considering the nurses availability, considering the capabilities and professional merits of nurses, fitness with social, cultural, and belief of people. The main themes were occupation analysis, planning and policy making, real workload, acceptability, nurses' efficiency, and being a native. Given that standardization of nursing staff estimation is announced as one of the challenges in reaching Iran's 20-year vision plan. Hence, design and implementation of a nursing staff estimation model in regard to identified features could be part of priorities in Ministry of Health in Iran.


Attractive Pickering Emulsion Gels.
Properties of emulsions highly depend on the interdroplet interactions and, thus, engineering interdroplet interactions at molecular scale are essential to achieve desired emulsion systems. Here, attractive Pickering emulsion gels (APEGs) are designed and prepared by bridging neighboring particle-stabilized droplets via telechelic polymers. In the APEGs, each telechelic molecule with two amino end groups can simultaneously bind to two carboxyl functionalized nanoparticles in two neighboring droplets, forming a bridged network. The APEG systems show typical shear-thinning behaviors and their viscoelastic properties are tunable by temperature, pH, and molecular weight of the telechelic polymers, making them ideal for direct 3D printing. The APEGs can be photopolymerized to prepare APEG-templated porous materials and their microstructures can be tailored to optimize their performances, making the APEG systems promising for a wide range of applications.


Design and fabrication of Sesamol-loaded transfersomal gel for wound healing: physicochemical characterization and in-vivo evaluation.
In the present study, an attempt has been made to develop SL-loaded transfersomal gel for the effective treatment of delayed wound healing. The wound healing process consists of a complex series of biochemical events and changes in cellular activity that restore the integrity of the skin and the subcutaneous tissue. Sesamol (SL), which is a natural phenolic compound, is known for its antioxidant properties, anti-inflammatory properties, and wound-healing abilities. A thin-film hydration method was used to prepare SL-loaded transfersomes. Different formulations containing Tween-80 and Span-80 as edge activators were prepared and optimized. Various characteristics of vesicles were assessed, such as size, shape, loading efficiency, deformability, and in vitro skin penetration. The optimized formulation was then incorporated into 1% carbopol 940 gel. An in vivo wound healing potential of the selected formulation was assessed by an excision wound model. The SL-loaded transfersomal gel displayed improved skin penetration and better skin deposition. Wound healing studies showed that the highest wound contraction was observed with SL-loaded transfersomes. Following 21 days of application of the transfersomal gel, a marked improvement in skin histological architecture was found. The study findings suggest that transfersomal gel has great potential as a therapeutic option in wound healing.


Thermodynamic Properties of Supported and Embedded Metallic Nanocrystals: Gold on/in SiO2.
We report on the calculations of the cohesive energy, melting temperature and vacancy formation energy for Au nanocrystals with different size supported on and embedded in SiO2. The calculations are performed crossing our previous data on the surface free energy of the supported and embedded nanocrystals with the theoretical surface-area-difference model developed by W. H. Qi for the description of the size-dependent thermodynamics properties of low-dimensional solid-state systems. Such calculations are employed as a function of the nanocrystals size and surface energy. For nanocrystals supported on SiO2, as results of the calculations, we obtain, for a fixed nanocrystal size, an almost constant cohesive energy, melting temperature and vacancy formation energy as a function of their surface energy; instead, for those embedded in SiO2, they decreases when the nanocrystal surface free energy increases. Furthermore, the cohesive energy, melting temperature and vacancy formation energy increase when the nanocrystal size increases: for the nanocrystals on SiO2, they tend to the values of the bulk Au; for the nanocrystals in SiO2 in correspondence to sufficiently small values of their surface energy, they are greater than the bulk values. In the case of the melting temperature, this phenomenon corresponds to the experimentally well-known superheating process.


Developing an engineered antimicrobial/prophylactic system using electrically activated bactericidal metals.
The increased use of Residual Hardware Devices (RHDs) in medicine combined with antimicrobial resistant-bacteria make it critical to reduce the number of RHD associated osteomyelitic infections. This paper proposes a surface treatment based on ionic emission to create an antibiotic environment that can significantly reduce RHD associated infections. The Kirby-Bauer agar gel diffusion technique was adopted to examine the antimicrobial efficacy of eight metals and their ionic forms against seven microbes commonly associated with osteomyelitis. Silver ions (Ag(+)) showed the most significant bactericidal efficacy. A second set of experiments, designed to identify the best configuration and operational parameters for Ag(+) based RHDs addressed current and ionic concentrations by identifying and optimizing parameters including amperage, cathode and anode length, separation between anode and cathode, and surface charge density. The system demonstrated an unparalleled efficacy. The concept was then implemented during in vitro testing of an antimicrobial hip implant, RHD.


Allogeneic hematopoietic stem-cell transplantation from haploidentical donors using 'ex-vivo' T-cell depletion in pediatric patients with hematological malignancies: state of the art review.
Nowadays, T-cell-depleted haploidentical transplantation is considered a valid approach for children lacking a human leukocyte antigen (HLA) identical donor for allogeneic transplantation. This kind of allogeneic transplant is now widely used especially for pediatric patients with high-risk hematological malignancies. However, relapsing disease and life-threatening viral infections are still relevant clinical problems as a consequence of delayed immune reconstitution. Adoptive cell therapies have been proposed to overcome this problem. After initial clinical approach using CD34+ selection as method for T-cell depletion (TCD), it was observed that immune reconstitution was delayed and it resulted on high incidence of opportunistic infections and nonrelapse mortality. It is now evident that development over time of graft manipulation techniques for TCD, have provide clinicians a useful tool for overcoming transplant complication such as graft failure, severe graft-vs.-host disease and opportunistic infections. As such, several procedures of almost total or partial TCD have been developed including CD3/CD19 depletion, T cell receptor αβ/CD19 depletion and more recently CD45RA+ depletion. Recent studies showed that immune reconstitution is associated with transplant outcomes. Based on this, haploidentical transplantation is now been explored as platform for cellular therapy to prevent disease recurrence or to treat clinical complications. Allogeneic transplantation still remains a standard of care for pediatric patients with high-risk hematological malignancies. In absence of an HLA identical donor, T-cell-depleted haploidentical transplant is now considered a valid option and provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.


Working memory test battery for young adults: Computerized working memory assessment.
This study developed a battery of computerized working memory (WM) tests and a scoring system suitable for young adult users. The tests comprised five classic tasks derived from Baddeley's model of WM, reflecting each of the five WM functions. We recruited 115 undergraduate and graduate students from various academic fields and constructed a preliminary WM scoring norm for young adults. The scoring norm was used as a basis for developing a computerized assessment system. The results of correlation analysis show that the fluid intelligence of young adults is related to the memory function of WM, but not to the central executive system. The proposed working memory test battery for young adults comprehensively reflects the WM capacity of adults.


Verapamil in acute myocardial infarction. The Danish Multicentre Study Group.
The reasons for starting a trial of verapamil in early intervention of acute myocardial infarction (AMI) are reviewed. In a pilot study of sixty-one patients it was demonstrated that verapamil probably had no harmful effects in patients with AMI. A multicentre study is now in progress in Denmark; 1433 have been included. Patients are treated with either placebo or verapamil 120 mg three times a day for 6 months. The results of the study, that is effect of verapamil treatment on death and reinfarction, will be available in 1982.


[Assessment of visual function and satisfaction in pseudophakic monovision].
To investigate the visual function and acceptability of pseudophakic monovision in relation to age. We examined 82 cases (age: 49-87 years) with pseudophakic monovision. All cases were undergone monovision using monofocal intraocular lens (IOLs). The cases were classified into three groups based on their age (A, less than 60 years; B, between 60 to 70 years ; and C, more than 70 years). Refractive error, visual acuity at various distances, contrast sensitivity, and near stereopsis were measured. Using a questionnaire, patient satisfaction before and after cataract surgery was evaluated. The mean difference in spherical equivalent refractive error between both eyes was 2.27 D (A, 2.39D; B, 2.30D; and C, 2.20 D). Most cases had a binocular uncorrected visual acuity of 20/25 or better at all distances. For contrast sensitivity, binocular summation was observed at 1.5 to 6 cycles/ degree. Near stereopsis was in the normal range, which was less than or equal to 100 seconds of arc. Moreover, it was found that 82% of the patients were satisfied with the results (A, 68%; B, 86%; and C, 93%). Pseudophakic monovision may be an effective approach for managing loss of accommodation after cataract surgery especially in patients over 60 years of age. However, careful selection of patients should be carried out.


Prevalence of risk factors and risk of mortality in relation to occupational group.
The aims of this study were to examine the prevalence of risk factors in different occupational groups of Kaunas men and women aged 35-64 years, and to assess the prognostic value of occupation on all-cause and cardiovascular mortality risk. The four random samples of Kaunas men and women (3,293 men and 3,561 women) aged 35-64 years from the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study (1983-2002) were examined using the standard epidemiological methods. The participants of the first three surveys were followed-up, in terms the end points reached, from the beginning of each survey until January 1, 2004. A multivariate Cox model was used for the analysis. In 1983-1984, the proportion of manual workers was greater than proportion of non-manual workers among both men and women. Twenty years later, the proportion of female manual workers decreased twice to 26.2%. The prevalence of majority risk factors showed no difference in manual and non-manual workers among both men and women. The risk of death from cardiovascular diseases among manual workers was 1.5 times greater than among non-manual workers. The different prognostic value of various variables has been determined on all-cause mortality risk in groups of manual and non-manual workers.


The selective TP receptor antagonist, S18886 (terutroban), attenuates renal damage in the double transgenic rat model of hypertension.
Thromboxane receptors play a decisive role in the renovascular actions of angiotensin II. We studied the efficacy of the selective thromboxane receptor antagonist, S18886, in the retardation of renal damage in the double transgenic rats (dTGR), harboring human renin and angiotensinogen genes. dTGR were gavaged daily with either S18886 (30 mg/kg/day, n = 12), or placebo (dTGR-Plac, tap water, n = 14) for 3 weeks. Matched Sprague-Dawley rats (n = 10) served as controls. The dTGR-Plac had higher systolic blood pressure (1.7-fold) than controls, and developed profound renal damage with significantly higher proteinuria (6.9-fold), polyuria (2.3-fold), index of glomerulosclerosis (+58%), and tubulointerstitial (+47%) and vascular damage scores (+19%). Creatinine concentration and the mesangiolysis index remained unchanged. In dTGR, S18886 slightly lowered the blood pressure (162 +/- 15 vs. 149 +/- 13 mm Hg, not significant) and improved proteinuria (558 +/- 218 vs. 136 +/- 71 mg/micromol creatinine, p < 0.01), polyuria and renal morphology (glomerulosclerosis index: 0.79 +/- 0.05 vs. 0.66 +/- 0.13, p < 0.01; tubulointerstitial damage index: 1.82 +/- 0.22 vs. 1.49 +/- 0.27, p < 0.05; mesangiolysis index: 1.31 +/- 0.18 vs. 0.36 +/- 0.09, p < 0.01). Vascular damage score and plasma creatinine were not influenced. S18886 did not alter measured markers of oxidative stress. The data present the first evidence that thromboxane receptor inhibition ameliorates angiotensin II-induced nephropathy.


Large improvement of RF transmission efficiency and reception sensitivity for human in vivo31P MRS imaging using ultrahigh dielectric constant materials at 7T.
In vivo31P MRS provides a unique and important imaging tool for studying high-energy phosphate metabolism and bioenergetics noninvasively. However, compared to 1H MRS, 31P MRS with a relatively low gyromagnetic ratio (γ) has a lower and limited sensitivity even at ultrahigh field. The proof of concept has been recently demonstrated that the use of high dielectric constant (HDC) materials between RF coil and object sample could increase MRI signal and reduce required RF transmission power for reaching the same RF pulse flip angle in the region of interest. For low-γ MRS applications operated at relatively lower frequency, however, it demands the dielectric materials with a much higher permittivity for achieving optimal performance. We conducted a 31P MRS imaging study using ultra-HDC (uHDC; with a relative permittivity of ~1200) material blocks incorporated with an RF volume coil at ultrahigh field of 7.0T. The experimental results from phantom and human calf muscle demonstrate that the uHDC technique significantly enhanced RF magnetic transmit field (B1+) and reception field (B1-) and the gain could reach up to two folds in the tissue near the uHDC blocks. The overall results indicate that the incorporation of the uHDC materials having an appropriate permittivity value with a RF coil can significantly increase detection sensitivity and reduces RF transmission power for X-nuclei MRS applications at ultrahigh field. The uHDC technology could provide an efficient, cost-effective engineering solution for achieving high detection sensitivity and concurrently minimizing tissue heating concern for human MRS and MRI applications.


Different job demands of nightshifts in hospitals.
It is now recognized that the effects of nightwork result jointly from desynchronization of circadian rhythms and from the job content. In scheduling nightwork, use should be made of the shift systems most compatible with the biological rhythms and social patterns of the workers concerned, and specific measures should be implemented to reduce demands on nightworkers. Job content is of particular importance in the hospital sector, where demands vary greatly from one department to another. Above all, the tasks accomplished by those on nightshift differ markedly from those of daytime workers: nightwork is limited to scheduled health care jobs that cannot be deferred until the morning, and to management of incidents. Yet staffing levels at night are reduced. Certain daytime resources are lacking at night, and the working conditions, generally defined with reference to the activities of daytime personnel fail to take into account the specific features of nightwork which are largely ignored by the management. On the basis of various studies conducted in French hospitals (extensive questionnaire surveys, ergonomic analyses in different departments), these features of nightwork and the corresponding need for appropriate responses, in terms of shift systems and job content, are reviewed and discussed.


The association between Cri du chat syndrome and dental anomalies.
Cri du chat syndrome (CdcS), also known as 5p deletion syndrome is a genetic disorder caused by the partial deletion of chromatin from the short arm of chromosome 5. There is a paucity of literature on the dental manifestations in CdcS. The purposes of this report are to present the case of a nine-year-old girl with the syndrome, CdcS and to review its dental and clinical manifestations and their management in children.


Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia.
Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated. Challenges include determination of the optimal level of D1R stimulation needed to improve cognitive performance, especially when D1R expression levels, affinity states, DA levels, and the resulting D1R occupancy by DA, are not clearly known in schizophrenia, and may display great interindividual and intraindividual variability related to cognitive states and other physiological variables. These directly affect the selection of the level of stimulation necessary to correct the underlying neurobiology. The optimal mechanism for stimulation is also unknown and could include partial or full agonism, biased agonism, or positive allosteric modulation. Furthermore, the development of D1R targeting drugs has been complicated by complexities in extrapolating from in vitro affinity determinations to in vivo use. Prior D1R-targeted drugs have been unsuccessful due to poor bioavailability, pharmacokinetics, and insufficient target engagement at tolerable doses. Newer drugs have recently become available, and these must be tested in the context of carefully designed paradigms that address methodological challenges. In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562.


An additive edge correction for the influence potential of trees.
The influence potential on a quadrat (IPQ) is an index for measuring the ecological effect that trees have on understory vegetation observed in a quadrat of a plot. IPQ is defined as the sum of the effect of every trees in the plot, where the effect depends on the size of the tree and the distance between the tree and the quadrat. Since only the trees in the plot have been observed and not the trees outside the plot, the true IPQ may be underestimated. Existing edge corrections are not appropriate for this case. We propose a correction that consists of adding the expected IPQ due to effects of trees outside the plot to the observed IPQ. The expectation is obtained by applying the Campbell theorem for stationary marked point processes. Data from the 1985-86 National Forest Inventory of Finland was used to calculate IPQ for six quadrats systematically allocated to each of 1240 plots. The implementation of the correction for this data is described. The distributions of IPQ with and without the correction proved the existence of edge effects and the effectiveness of the correction to eliminate the bias. This method has the potential to be applied to other additive functions.


Medical male circumcision: How does price affect the risk-profile of take-up?
The benefit of male circumcision is greatest among men who are most at risk of HIV infection. Encouraging this population of men to get circumcised maximizes the benefit that can be achieved through the scale-up of circumcision programs. This paper examines how the price of circumcision affects the risk profile of men who receive a voluntary medical circumcision. In 2010, 1649 uncircumcised adult men in urban Malawi were interviewed and provided a voucher for a subsidized voluntary medical male circumcision, at randomly assigned prices. Clinical data were collected indicating whether the men in the study received a circumcision. Men who took-up circumcision with a zero-priced voucher were 25 percentage points less likely than those who took-up with a positive-price voucher, to be from a tribe that traditionally circumcises (p=0.101). Zero-priced vouchers also brought in men with more sexual partners in the past year (p=0.075) and past month (p=0.003). None of the men who were most at risk of HIV at baseline (those with multiple partners and who did not use a condom the last time they had sex) received a circumcision if they were offered a positive-priced voucher. Lowering the price to zero increased circumcision take-up to 25% for men of this risk group. The effect of price on take-up was largest among those at highest risk (p=0.096). Reducing the price of circumcision surgery to zero can increase take-up among those who are most at risk of HIV infection.


Quantitative changes of extravillous trophoblast cells in heavy smoker mothers compared with healthy controls.
Maternal smoking during pregnancy can induce structural and functional changes in the placenta. Placentas from heavy smoker (>20 cigarettes per day) mothers and non-smoker healthy controls (n=10 in each group) were enrolled in the present case-control study. Sample selection and sectioning were performed by systematic uniform random sampling (SURS). Selected sections were stained using Masson's trichrome to estimate quantitative parameters of placental extravillous trophoblast cells (EVTs) and the number of EVTs. Differences between groups were evaluated using the Mann-Whitney U-test, with significance set at P<0.05. There was a significant difference in placental weight and the total volume of the placenta between the heavy smoker and control groups (P<0.05). The total volume of EVTs, nucleus diameter, cytoplasm diameter, the volume of the nucleus and cytoplasm and the nucleus to cytoplasm ratio of EVTs were significantly greater in the heavy smoker compared with control group (P<0.05 for all). In placentas from heavy smokers, the total number of EVTs per unit volume of placental bed were significantly greater than in the control group (P<0.05 for both). In conclusion, the findings suggest that maternal smoking could affect fetal health by changing the quantitative parameters of the placenta, and likely the invasive properties of EVTs.


Vestibular evoked myogenic potentials in children.
The aim of this work is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test of vestibular function in children. Forty normal hearing children, aged between 3 and 15 years, and classified in preschool and scholar group, have been investigated in order to study normal development of vestibular potentials and to define fundamental parameters of VEMPs, establishing normal data of latencies and amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was recorded while children were laid supine on a bed and asked to raise their head off of the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500Hz at an intensity of 130dB peSPL presented monaurally through earphones. In each recording, we analysed latencies and amplitudes of the p13 and n23 waves and the amplitude ratio between the two ears. VEMPs were normally detected in all subjects. In preschool group mean p13 and mean n23 latencies were, respectively, 16.13 (+/-2.12)ms and 21.17 (+/-2.77)ms; mean amplitude ratio was 28.49 (+/-18.10). In scholar group mean p13 and n23 were respectively 16.14 (+/-3.48)ms and 21.78 (+/-3.39)ms, while mean amplitude ratio 20.44 (+/-13.24). Comparison of latencies and amplitude ratio between the children groups and control adult group did not showed any significant differences. In conclusion, VEMPs could represent a valid and non-invasive technique able to investigate vestibular function in children and, in particular, vestibulo collic reflex.


[Quantification of the PRAME transcripts in patients with acute myeloid leukemia].
To analyze the expression level and clinical significance of the preferentially expressed antigen of melanoma (PRAME) transcripts in patients with acute myeloid leukemia (AML). Real-time quantitative polymerase chain reaction with EvaGreen dye was established to detect the expression level of PRAME transcripts in the bone marrow mononuclear cells of 56 AML cases and 20 controls. The clinical association of PRAME transcripts was analyzed. The PRAME transcripts were 0-1.46% (median 0.18%) and 0-21 618.09% (median 9.79%) in controls and AML cases, respectively (P< 0.01). Among the FAB subtypes, those with M1, M2, M3 and M4 had significantly higher level of PRAME transcripts than controls. However, those with M5 had similar level of PRAME transcripts as controls. There was a significantly negative correlation between the PRAME transcripts and cytogenetic risk groups (r= -0.438, P= 0.001). Cases in low risk had significantly higher level of PRAME transcripts than those in intermediate and high risk. Among cases with AML-M2, those with t(8;21) had significantly higher level of PRAME transcripts (135.06% -21 618.09%, median 2201.88%) than those without t(8;21)(0.14% -1696.30%, median 17.97%)(P= 0.002). In a patient with sequential samples, PRAME transcripts significantly decreased after induction therapy and significantly increased after relapse. The PRAME transcript was highly expressed in AML patients and was a favorable marker of prognosis. Quantification of PRAME transcript can be used in monitoring disease status of AML.


Stimulation by extracellular ATP and UTP of the stress-activated protein kinase cascade in rat renal mesangial cells.
1. Extracellular adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) have been shown to activate a nucleotide receptor (P2U receptor) in rat mesangial cells that mediates phosphoinositide and phosphatidylcholine hydrolysis by phospholipases C and D, respectively. This is followed by an increased activity of the mitogen-activated protein kinase cascade and cell proliferation. Here we show that ATP and UTP potently stimulate the stress-activated protein kinase pathway and phosphorylation of the transcription factor c-Jun. 2. Both nucleotides stimulated a rapid (within 5 min) and concentration-dependent activation of stress-activated protein kinases as measured by the phosphorylation of c-Jun in a solid phase kinase assay. 3. When added at 100 microM the rank order of potency of a series of nucleotide analogues for stimulation of c-Jun phosphorylation was UTP > ATP = UDP = ATP gamma S > 2-methylthio-ATP > beta gamma-imido-ATP = ADP > AMP = UMP = adenosine = uridine. Activation of stress-activated protein kinase activity by ATP and UTP was dose-dependently attenuated by suramin. 4. Down-regulation of protein kinase C-alpha, -delta and -epsilon isoenzymes by 24 h treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate did not inhibit ATP- and UTP-induced activation of c-Jun phosphorylation. Furthermore, the specific protein kinase C inhibitors, CGP 41251 and Ro 31-8220, did not inhibit nucleotide-stimulated c-Jun phosphorylation, suggesting that protein kinase C is not involved in ATP- and UTP-triggered stress-activated protein kinase activation. 5. Pretreatment of the cells with pertussis toxin or the tyrosine kinase inhibitor, genistein, strongly attenuated ATP- and UTP-induced c-Jun phosphorylation. Furthermore, N-acetyl-cysteine completely blocked the activation of stress-activated protein kinase in response to extracellular nucleotide stimulation. 6. In summary, these results suggest that ATP and UTP trigger the activation of the stress-activated protein kinase module in mesangial cells by a pathway independent of protein kinase C but requiring a pertussis toxin-sensitive G-protein and tyrosine kinase activation.


[Thyroid hormone metabolism and action].
Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads to the activation or inactivation of the thyromimetic activity inherent to thyroid hormones. Alterations in the activities of the three selenocysteine-containing enzymes, the iodothyronine deiodinases, have been reported during development and in specific cells and tissues of the adult organism. Furthermore, pathophysiological changes in the deiodinase expression lead to therapeutically relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side chain or cleavage of their diphenylether bridge also contributes to both local and systemic supply of thyromimetic activity or hormone degradation. Further components mediating the pleiotropic action of thyroid hormones in part include redundant T3 receptors, binding and transport proteins, metabolising enzymes and T3-regulated gene products. This is achieved in a finely tuned manner with multiple feedback control, malfunction or complete failure of individual components and networks involved in the iodothyronine metabolism and thyroid hormone action can thus be compensated or prevented.


Nonspecific effect of bis(2-ethylhexyl) phthalate on hexobarbital sleep time.
The data presented suggest that the intravenous or intraperitoneal administration of bis(2-ethylhexyl) phthalate prolongs hexobarbital sleep time in mice and rats by enlarging the lipophilic pool, a phenomenon that can be replicated by pretreatment of the animals with olive oil. These results call attention to the importance of considering the physical characteristics of a substance when evaluating its effect on a pharmacologically active agent.


Comparative gene expression analysis of Porphyromonas gingivalis ATCC 33277 in planktonic and biofilms states.
Porphyromonas gingivalis is a keystone pathogen in the onset and progression of periodontitis. Its pathogenicity has been related to its presence and survival within the subgingival biofilm. The aim of the present study was to compare the genome-wide transcription activities of P. gingivalis in biofilm and in planktonic growth, using microarray technology. P. gingivalis ATCC 33277 was incubated in multi-well culture plates at 37°C for 96 hours under anaerobic conditions using an in vitro static model to develop both the planktonic and biofilm states (the latter over sterile ceramic calcium hydroxyapatite discs). The biofilm development was monitored by Confocal Laser Scanning Microscopy (CLSM) and Scanning Electron Microscopy (SEM). After incubation, the bacterial cells were harvested and total RNA was extracted and purified. Three biological replicates for each cell state were independently hybridized for transcriptomic comparisons. A linear model was used for determining differentially expressed genes and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to confirm differential expression. The filtering criteria of ≥ ±2 change in gene expression and significance p-values of <0.05 were selected. A total of 92 out of 1,909 genes (4.8%) were differentially expressed by P. gingivalis growing in biofilm compared to planktonic. The 54 up-regulated genes in biofilm growth were mainly related to cell envelope, transport, and binding or outer membranes proteins. Thirty-eight showed decreased expression, mainly genes related to transposases or oxidative stress. The adaptive response of P. gingivalis in biofilm growth demonstrated a differential gene expression.


Foreign body giant cells selectively covering haptics of intraocular lens implants: indicators of poor toleration?
A Sputnik lens implant removed after five years because of bullous keratopathy exhibits a dense covering of its Supramid anterior staves with large foreign body giant cells, while its Prolene loops and Polymethylmethacrylate optics have attracted only few of these cell units. The glass-membrane-like component of the reactive membrane also shows significant differences on the different parts of this implant. The use of observation of the components of reactive membranes on lens implants as indicators of toleration in the eye is suggested.


Eosinophilic granulomatosis with polyangitis: A new target for biologicals.
Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.


Validity of the Rotterdam Symptom Checklist in paediatric oncology.
In order to determine the validity of the Rotterdam Symptom Checklist (RSC) for use with paediatric patients, a sample of 47 mothers with a child with acute lymphoblastic leukaemia (ALL) was asked to complete the RSC, the Play Performance Scale for Children PPSC and a measure of daily activity (HDI: Questionnaires were completed during routine outpatient visits. There were no effects of child age on number of symptoms reported. The physical symptom subscale of the RSC distinguished between children in terms of treatment status and number of hospitalisations. However, the psychological symptom subscale did not distinguish between these groups. Limitations of the scale for work with children are considered. These include difficulties experienced by patents in reporting psychological symptoms for their children, and the inappropriateness of a scale developed for adults to assess children. In the absence of other measures, the RSC can be used for children, but a more developmentally appropriate measures is needed.


[Idiopathic eosinophilic esophagitis: a frequently overlooked disease with typical clinical aspects and discrete endoscopic findings].
In 10 patients presenting with acute recurrent dysphagia, seen over a 4-year period, idiopathic, eosinophilic esophagitis (IEE) was diagnosed. The diagnosis was confirmed histologically. Dysphagia of other causes or other diseases causing eosinophilic infiltration was ruled out. Endoscopy showed discrete white structures in the esophagus which were partly finely reticular or plaque-like in 9 of the 10 patients. Of these one had a web and another a mucosal ring. Peripheral eosinophilia and elevated IgE-levels were found in 70% of the cases. To date IEE has been thought to be a rare disorder. Emerging evidence suggests its prevalence has been underestimated. It may also be the most frequent form of eosinophilic gastroenteropathy. The flat, only endoscopically visible form may be more common than the proliferative type. With knowledge of the typical history and of the distinct endoscopic pattern, and with adequate diagnostic workup, the disease will be found more often in the future. Prompt diagnosis also avoids further diagnostic procedures and permits rapid remission through treatment with steroids and antihistamines.


Copper(II) Complexes of Cyclams Containing Nitrophenyl Substituents: Push-Pull Behavior and Scorpionate Coordination of the Nitro Group.
The three nitrophenyl-cyclam derivatives (nitrocyclams): 1-(4-nitrophenyl)-1,4,8,11-tetraazacyclotetradecane (2), 1-(2-nitrophenyl)-1,4,8,11-tetraazacyclotetradecane (3), and 1-(2,4-dinitrophenyl)-1,4,8,11-tetraazacyclotetradecane (4), in an MeCN solution, specifically incorporate the Cu(II) ion according to an irreversible process signaled by disappearance of the yellow color for a concentration c < 1 × 10(-4) M and by a yellow-to-red color change for c ≥ 1 × 10(-3), and must be considered efficient and specific dosimeters of copper(II) salts. When present in the ortho position of the nitrophenyl substituent, the -NO2 group coordinates the Cu(II) according to a scorpionate mode, while the metallocyclam system exhibits a trans-I configuration. In an MeCN solution the red trans-I-[Cu(II)(3)](2+) and trans-I-[Cu(II)(4)](2+) scorpionate complexes slowly convert into the violet trans-III scorpionate complexes. Kinetic aspects of the trans-I-to-trans-III configurational rearrangement were investigated in detail for the [Cu(II)(4)](2+) system. In particular, the conversion is spectacularly accelerated by catalytic amounts of Cl(-), NCO(-), and F(-). While for Cl(-) and NCO(-) the effect can be associated with the capability of the anion to stabilize through coordination a possible dissociative intermediate, the amazingly powerful effect of F(-) must be related to the preliminary deprotonation of one N-H fragment of the macrocycle, driven by the formation of the HF2(-) ion. Most of the metal complex species studied in solution were isolated in a crystalline form, and their molecular structures were elucidated through X-ray diffraction studies. This study documents the first examples of effective metal coordination by the nitro group.


[Iliopsoas abscess accompanied by epidural abscess--a case report].
A 55-year-old man was admitted to a hospital with pain of the low back as well as the left leg, and fever. He was suspected of suffering from the lumbar disc herniation because of the presence of Lasegue's sign on the first physical examination. Abdominal computed tomography, however, revealed the swelling of the left iliopsoas muscle. Iliopsoas abscess accompanied epidural abscess was confirmed by subsequent magnetic resonance imaging (MRI). Antibiotic therapy was started for the successive 8 days. The fever resolved, but the pain persisted. The abscess extending from the iliopsoas muscle to the epidural space was still seen on the MRI 20 days after the completion of the antibiotic therapy, and he still complained of the pain of his low back and left leg. Therefore, we conducted epidural puncture under fluoroscopic guidance. Approximately 3 ml of pus was aspirated from the epidural space. Then, his complains decreased remarkably. Iliopsoas abscess should be taken into account in case of a patient with pain on the low back and leg and also inflammatory signs such as fever and leucocytosis.


Fibrosarcoma with deceptive benign presentations: a report of two cases.
Low-grade fibromyxoid sarcoma and myxofibrosarcoma are malignant soft tissue tumors, fibrosarcomas, of shared clinical and imaging appearances. We report sarcomatous lesions in soft tissue with deceptively benign clinical and imaging appearances, and correlate findings with those of histologic analysis. Two patients presented with a long history of painless swelling at the dorsum and upper extremity and denied any constitutional symptoms. Sonography and magnetic resonance imaging suggested the presence of benign soft tissue lesions of a predominant fluid-like consistency. Despite indolent clinical and imaging characteristics, in both cases, histopathology disclosed a diagnosis of spindle cell-type soft tissue sarcoma, designating an aggressive tumor. Knowledge of the seemingly benign clinical and imaging features of fibrosarcomas is required to raise the possibility of malignancy in soft tissue that may be underdiagnosed or misdiagnosed. The importance of a correct diagnosis and the implications of surgical resection, irradiation, and systemic oncological therapy are quite obvious.


Intake of dietary flavonoids and incidence of ischemic heart disease in the Danish Diet, Cancer, and Health cohort.
Few studies have investigated the association between dietary flavonoid intake, including all major subclasses, and the long-term risk of ischemic heart disease (IHD). We examined whether dietary flavonoid intake associated with IHD incidence, assessing the possible modifying role of sex and smoking, in participants from the Danish Diet, Cancer, and Health study. In a cohort study design, 54,496 adults (46.8% male), aged 50-64 years, without a history of IHD, were followed for up to 23 years. Habitual dietary flavonoid intake was estimated from food frequency questionnaires using Phenol-Explorer. Incident cases of IHD were identified within Danish nationwide health registries. Restricted cubic splines in Cox proportional hazards models were used to examine associations between flavonoid intake and IHD risk. During follow-up, 5560 IHD events were recorded. No overall association was seen between total flavonoid intake, nor any subclass, and IHD, following adjustment for demographics, lifestyle, and dietary confounders. Stratified by sex and smoking status, higher intakes of specific subclasses associated with lower IHD risk among ever-smokers [Q5 vs. Q1 flavonols HR (95% CI): 0.90 (0.82, 0.99); flavanol oligo+polymers: 0.88 (0.80, 0.97)], but not among never-smokers, nor either sex specifically. While we did not find clear evidence that higher habitual dietary flavonoid intake was associated with lower IHD risk, these results do not exclude the possibility that certain subclasses may have a protective role in prevention of IHD among population sub-groups; this was evident among smokers, who are at a higher risk of atherosclerosis.


Synthesis and Characterization of a Poly(ethylene glycol)-Poly(simvastatin) Diblock Copolymer.
Biodegradable polyesters are commonly used as drug delivery vehicles, but their role is typically passive, and encapsulation approaches have limited drug payload. An alternative drug delivery method is to polymerize the active agent or its precursor into a degradable polymer. The prodrug simvastatin contains a lactone ring that lends itself to ring-opening polymerization (ROP). Consequently, simvastatin polymerization was initiated with 5 kDa monomethyl ether poly(ethylene glycol) (mPEG) and catalyzed via stannous octoate. Melt condensation reactions produced a 9.5 kDa copolymer with a polydispersity index of 1.1 at 150 °C up to a 75 kDa copolymer with an index of 6.9 at 250 °C. Kinetic analysis revealed first-order propagation rates. Infrared spectroscopy of the copolymer showed carboxylic and methyl ether stretches unique to simvastatin and mPEG, respectively. Slow degradation was demonstrated in neutral and alkaline conditions. Lastly, simvastatin, simvastatin-incorporated molecules, and mPEG were identified as the degradation products released. The present results show the potential of using ROP to polymerize lactone-containing drugs such as simvastatin.


[Lumbar spondylosis].
Lumbar spondylosis is a chronic, noninflammatory disease caused by degeneration of lumbar disc and/or facet joints. The etiology of lumbar spondylosis is multifactorial. Patients with lumbar spondylosis complain of a broad variety of symptoms including discomfort in the low back lesion, whereas some of them have radiating leg pain or neurologenic intermittent claudication (lumbar spinal stenosis). The majority of patients with spondylosis and stenosis of the lumbosacral spine can be treated nonsurgically. Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors are helpful in controlling symptoms. Prostaglandin, epidural injection, and transforaminal injection are also helpful for leg pain and intermittent claudication. Operative therapy for spinal stenosis or spondylolisthesis is reserved for patients who are totally incapacitated by their condition.


The Premedical Student: Training and Practice Expectations.
Occupational burnout is a substantial and growing problem among current medical practitioners. Many practicing physicians lament the encroachment of managed care, infringement of physician autonomy by insurers, decreasing salaries, and decreasing prestige. In light of this unfavorable review of the profession, why are thousands of undergraduates all over the country still on the premedical track? Do these young men and women really know what kind of work environment awaits them at the end of their arduous training program? What motivates them to become physicians? In this case study, we explore the reasons for pursuing a career in medicine among a sample of premedical students at a liberal arts college on the East Coast. College administrators agree that the pre-medical curriculum is one of the most demanding and arduous study programs. What do these pre-medical students see as the ultimate goal? As a result of various volunteer, training, and shadowing experiences in the medical field, many of these students have a realistic perception of the current environment of medical practice. Although they recognize the challenges that await them, they are driven to become doctors by a deep vocational calling to serve. However, not all of the students expressed this calling. Results from this study suggest that eventual career satisfaction may be correlated with baseline career motivations. Students who are becoming doctors to fulfill parents' aspirations, for upward mobility, and/or for prestige and high salaries may be disenchanted once they complete their training program.


Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats.
Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p = 0.0017) and AST levels (p = 0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p < 0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.


Quantitative EEG effects of nicotine replacement by cigarette smoking.
The effects of cigarette smoking on the central nervous system can be assessed directly using the electroencephalogram (EEG). Nicotine withdrawal and subsequent replacement have been studied, but have produced conflicting effects on brain electrical activity. We studied the effect of smoking 2 cigarettes at subjects' own pace in 20 subjects. EEG was recorded using the EEGSYS program in the eyes-closed awake state using a bipolar montage. Delta power decreased in central-posterior head regions. Theta power and power in the lower half of the alpha band decreased. Beta power and power in the upper half of the alpha band increased significantly over frontotemporal head regions. Examination of spectra underlying the usual frequency bands revealed that many effects of smoking on EEG power probably resulted from a shift of the overall power spectrum toward higher frequencies, rather than resulting from alterations in activity in specific frequency bands.


Limbic corticostriatal systems and delayed reinforcement.
Impulsive choice, one aspect of impulsivity, is characterized by an abnormally high preference for small, immediate rewards over larger delayed rewards, and can be a feature of adolescence, but also attention-deficit/hyperactivity disorder (ADHD), addiction, and other neuropsychiatric disorders. Both the serotonin and dopamine neuromodulator systems are implicated in impulsivity; manipulations of these systems affect animal models of impulsive choice, though these effects may depend on the receptor subtype and whether or not the reward is signaled. These systems project to limbic cortical and striatal structures shown to be abnormal in animal models of ADHD. Damage to the nucleus accumbens core (AcbC) causes rats to exhibit impulsive choice. These rats are also hyperactive, but are unimpaired in tests of visuospatial attention; they may therefore represent an animal model of the hyperactive-impulsive subtype of ADHD. Lesions to the anterior cingulate or medial prefrontal cortex, two afferents to the AcbC, do not induce impulsive choice, but lesions of the basolateral amygdala do, while lesions to the orbitofrontal cortex have had opposite effects in different tasks measuring impulsive choice. In theory, impulsive choice may emerge as a result of abnormal processing of the magnitude of rewards, or as a result of a deficit in the effects of delayed reinforcement. Recent evidence suggests that AcbC-lesioned rats perceive reward magnitude normally, but exhibit a selective deficit in learning instrumental responses using delayed reinforcement, suggesting that the AcbC is a reinforcement learning system that mediates the effects of delayed rewards.


Efficient Hydrogen Delivery for Microbial Electrosynthesis via 3D-Printed Cathodes.
The efficient delivery of electrochemically in situ produced H2 can be a key advantage of microbial electrosynthesis over traditional gas fermentation. However, the technical details of how to supply large amounts of electric current per volume in a biocompatible manner remain unresolved. Here, we explored for the first time the flexibility of complex 3D-printed custom electrodes to fine tune H2 delivery during microbial electrosynthesis. Using a model system for H2-mediated electromethanogenesis comprised of 3D fabricated carbon aerogel cathodes plated with nickel-molybdenum and Methanococcus maripaludis, we showed that novel 3D-printed cathodes facilitated sustained and efficient electromethanogenesis from electricity and CO2 at an unprecedented volumetric production rate of 2.2 L CH4 /L catholyte /day and at a coulombic efficiency of 99%. Importantly, our experiments revealed that the efficiency of this process strongly depends on the current density. At identical total current supplied, larger surface area cathodes enabled higher methane production and minimized escape of H2. Specifically, low current density (<1 mA/cm2) enabled by high surface area cathodes was found to be critical for fast start-up times of the microbial culture, stable steady state performance, and high coulombic efficiencies. Our data demonstrate that 3D-printing of electrodes presents a promising design tool to mitigate effects of bubble formation and local pH gradients within the boundary layer and, thus, resolve key critical limitations for in situ electron delivery in microbial electrosynthesis.


Grief response of parents to neonatal death and parent participation in deciding care.
We determined the grief response to neonatal death of 50 mother-father pairs by administering a questionnaire and conducting a semistructured interview during the infant postmortem review. As measured by a parent grief score, maternal grief significantly exceeded paternal grief (t = 5.89, P less than .0001). Parent grief was not significantly related to birth weight, duration of life, extent of parent-infant contact, previous perinatal loss, parent age, or distance from the hospital of birth to the regional center (Pearson product-moment correlation coefficients). However, the attitudes and behavior of family, friends, and health care personnel in the hospital of birth often adversely influenced parent grieving. Of 39 mother-father pairs whose infants required respirator support, 18 participated in a group decision with their physician to withdraw respirator support when the prospects of infant survival seemed hopeless (limited respirator care group). No significant differences in parent grief scores were found (t tests) when the limited respirator care group was compared to those parents of infants who died despite uninterrupted respirator care. Our data suggest that informed parents can participate as partners with their physician in difficult infant care decision, even when death results, and adjust to their loss with healthy grieving.


Atypical location of lipoblastoma in a 5-year-old girl.
We reported a perineal lipoblastoma in a 5-year-old girl located in the right labia mayor. The lesion gradually increased within 6 months. Ultrasound and magnetic resonance imaging (MRI) showed a limited solid heterogenous tumor with fatty component. After it had been surgically removed, the anatomopathological examination confirmed that it was a lipoblastoma. Lipoblastoma is a rare benign mesenchymal tumor of infancy and early childhood. Symptoms vary depending on localization; signs of compression of adjacent organs may be seen. This type of unusual soft tissue tumors occurred most often in under 3 years old. The localization of lipoblastomas is predominantly in the extremities but may be also found in other sites including the head and neck, trunk, mediastinum, kidney, mesentery, retropritoneum and perineum. The suspicion should be considered according to ultrasound and MRI findings.


A newly designed disposable introducer sheath for a ventricular fiberscope.
We have developed a disposable plastic introducer sheath for use with a flexible endoscope during intraventricular procedures. The sheath is composed of a thin polypropylene tube passing through the center of a plastic stopper. The tube serves as a sheath through which the fiberscope is introduced into the ventricle. The stopper seats in the burr hole and prevents downward and lateral movement of the tube. The sheath can be placed safely in the ventricle with a drainage catheter used as an introducing guide. We used this sheath system in 10 patients and found it very useful. Manipulation of the fiberscope was not hindered, copious irrigation was allowed, and the sheath remained stable on the skull. This new introducer sheath may contribute to the increased use of a flexible endoscope in neuroendoscopic procedures.


Fatigue-related firing of muscle nociceptors reduces voluntary activation of ipsilateral but not contralateral lower limb muscles.
During fatiguing upper limb exercise, maintained firing of group III/IV muscle afferents can limit voluntary drive to muscles within the same limb. It is not known if this effect occurs in the lower limb. We investigated the effects of group III/IV muscle afferent firing from fatigued ipsilateral and contralateral extensor muscles and ipsilateral flexor muscles of the knee on voluntary activation of the knee extensors. In three experiments, we examined voluntary activation of the knee extensors by measuring changes in superimposed twitches evoked by femoral nerve stimulation. Subjects attended on 2 days for each experiment. On one day a sphygmomanometer cuff occluded blood flow of the fatigued muscles to maintain firing of group III/IV muscle afferents. After a 2-min extensor contraction (experiment 1; n = 9), mean voluntary activation was lower with than without maintained ischemia (47 ± 19% vs. 87 ± 8%, respectively; P < 0.001). After a 2-min knee flexor maximal voluntary contraction (MVC) (experiment 2; n = 8), mean voluntary activation was also lower with than without ischemia (59 ± 21% vs. 79 ± 9%; P < 0.01). After the contralateral (left) MVC (experiment 3; n = 8), mean voluntary activation of the right leg was similar with or without ischemia (92 ± 6% vs. 93 ± 4%; P = 0.65). After fatiguing exercise, activity in group III/IV muscle afferents reduces voluntary activation of the fatigued muscle and nonfatigued antagonist muscles in the same leg. However, group III/IV muscle afferents from the fatigued left leg had no effect on the unfatigued right leg. This suggests that any "crossover" of central fatigue in the lower limbs is not mediated by group III/IV muscle afferents.


Evidence that the median raphé nucleus--dorsal hippocampal pathway mediates diazepam withdrawal-induced anxiety.
On the basis of our previous series of experiments we had postulated that the increased anxiety that occurred during diazepam withdrawal was mediated by increased 5-HT release in the hippocampus. The present series of experiments provide evidence for a major role of the median raphé nucleus (MRN) dorsal hippocampal pathway. Rats were treated once daily for 21 days with diazepam (2 mg/kg IP) and then tested after 24 h withdrawal in the social interaction test of anxiety. Relative to chronically vehicle treated animals, those withdrawn from diazepam were significantly more anxious and had significantly greater K(+)-evoked release of [3H]-5-hydroxytryptamine (5-HT) from slices of dorsal and of ventral regions of the hippocampus. Estimation of extracellular concentrations of 5-HT within the dorsal hippocampus, using in-vivo microdialysis, showed doubling in the levels of 5-HT in the rats withdrawn from chronic diazepam treatment. This just failed to reach significance, but 33% of the rats showed dramatic increases (650%). It was not possible to test these animals in the social interaction test, but it is proposed that only the diazepam-withdrawn rats with raised extracellular levels of 5-HT would have displayed increased anxiety. 5-HT1A receptor agonists injected into the MRN decrease the MRN firing rate, and hence the release of 5-HT in the dorsal hippocampus. As a further test of our hypothesis, we examined the effects of MRN injection of the 5-HT1A receptor agonist, 8-OH DPAT, on animals withdrawn from diazepam and tested in the low light familiar condition of the social interaction test. 8-OH DPAT (50-200 ng) dose-dependently reversed the anxiogenic effect of diazepam withdrawal, while having no effects in chronic vehicle-treated animals. These results provide clear evidence that the MRN-dorsal hippocampal 5-HT pathway is at least one of the pathways playing an important role in mediating diazepam withdrawal-induced anxiety.


Psychoactive drugs and neuroplasticity.
The influence of psychoactive drugs on neuroplasticity, especially on neurogenesis is reviewed. From psychopharmacological point of view most interesting results are those showing neurogenesis that neurogenesis is increased by SSRI. However, the role of serotonin system in neurogenesis as well as significance of neurogenesis in the beneficial effect of psychotropic drugs requires a lot of additional and new inventive research.


R-Ras induces malignant, but not morphologic, transformation of NIH3T3 cells.
Although previous studies have not identified transforming properties of the Ras-related protein R-Ras, two recent observations have prompted our further evaluation of R-Ras function. First, we observed that mutant forms of the closely related R-Ras2/TC21 protein (approximately 70% identity) exhibited the same potent transforming activity as oncogenic Ras proteins. Second, R-Ras association with Bcl-2 suggested a possible role for R-Ras in apoptotic growth control. Therefore, we have performed a detailed analysis of R-Ras transforming potential in NIH3T3 cells. Whereas expression of a mutant R-Ras protein (38V; analogous to the 12V activating Ras mutation) did not induce morphologic transformation of NIH3T3 cells, R-Ras(38V)-expressing cells proliferated in low serum, formed colonies in soft agar, and formed progressive tumors in nude mice. Like Ras-transformed cells, R-Ras(38V)-transformed cells exhibited constitutively activated mitogen activated protein kinases. Furthermore, R-Ras(38V) stimulated transcriptional activation of Ras-responsive promoter elements, and this activity (and transformation) was blocked by Raf dominant negative proteins. Finally, whereas co-expression of Bcl-2 did not cause significant alteration in wild type or mutant R-Ras transforming activity, coexpression of v-Myc and R-Ras(38V) induced a striking morphologic transformation of NIH3T3 cells. Taken together, these observations suggest that aberrant R-Ras function may stimulate malignant transformation, in the absence of morphologic transformation, via up-regulation of part of the Ras signal transduction pathway.


Intraindividual variation in the basal metabolic rate of women: Effect of the menstrual cycle.
The validity of using the basal metabolic rate (BMR) to calculate an individual's energy requirements is based upon the assumption that the intraindividual variation in BMR is small. Early studies (pre-1940) on BMR in women had shown that the menstrual cycle may have a profound effect, contributing to high levels of intraindividual variation. To investigate this issue further, and to explore whether BMR is indeed a biological constant in women, sequential measurements of BMR were made in women over one menstrual cycle. Two independent studies were undertaken in which the BMR of 12 weight-stable women (not taking the contraceptive pill) was measured every day (excluding weekends) for a period of 5 weeks. The six women participating in the first study were measured using a Douglas bag, while the six subjects in the second study were measured with a Deltatrac (Datex, Helsinki). Nine of the 12 subjects demonstrated a peak in BMR during the late luteal phase of the menstrual cycle, while 8 of the 12 subjects exhibited a fall in BMR after the onset of menstruation. Group analysis of the results indicated that the BMR during the early follicular phase was significantly lower than the BMR during the late luteal phase (Wilcoxon's signed rank test: P < 0.01). The level of intraindividual variation was assessed by calculating the coefficient of variation (CV) for the measurement period. The CV in six of the women exhibited a level of variation comparable to men (2-4%). However, intraindividual variation in the BMR of the other six women was considerably higher (up to 12%). In these six women, therefore, BMR may not be considered a biological constant. All available data on sequential measurements of BMR in fertile women were collated from the literature for the first time, and statistically analyzed. BMR during the early follicular phase was found to be significantly lower (P < 0.05) than during the late luteal phase. Further work on the biological constancy of BMR in women and the impact of the menstrual cycle on BMR is required. This area is of particular importance given the fact that the energy requirements of both individuals and populations are now calculated using the BMR. © 1996 Wiley-Liss, Inc.


Passive Way of Measuring QOL/Well-Being Levels Using Smartphone Log.
Research on mental health states involves paying increasing attention to changes in daily life. Researchers have attempted to understand such daily changes by relying on self-reporting through frequent assessment using devices (smartphones); however, they are mostly focused on a single aspect of mental health. Assessing the mental health of a person from various perspectives may help in the primary prevention of mental illness and the comprehensive measurement of mental health. In this study, we used users' smartphone logs to build a model to estimate whether the scores on three types of questionnaires related to quality of life and well-being would increase compared to the previous week (fluctuation model) and whether they would be higher compared to the average for that user (interval model). Sixteen participants completed three questionnaires once per week, and their smartphone logs were recorded over the same period. Based on the results, estimation models were built, and the F-score ranged from 0.739 to 0.818. We also analyzed the features that the estimation model emphasized. Information related to "physical activity," such as acceleration and tilt of the smartphone, and "environment," such as atmospheric pressure and illumination, were given more weight in the estimation than information related to "cyber activity," such as usage of smartphone applications. In particular, in the Positive and Negative Affect Schedule (PANAS), 9 out of 10 top features in the fluctuation model and 7 out of 10 top features in the interval model were related to activities in the physical world, suggesting that short-term mood may be particularly heavily influenced by subjective activities in the human physical world.


Novel COL4A2 variant in a large pedigree: Consequences and dilemmas.
Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.


Specific sequences in the N and C termini of apolipoprotein A-IV modulate its conformation and lipid association.
Apolipoprotein (apoA-IV) is a 376-residue exchangeable apolipoprotein that may play a number of important roles in lipid metabolism, including chylomicron assembly, reverse cholesterol transport, and appetite regulation. In vivo, apoA-IV exists in both lipid-poor and lipid-associated forms, and the balance between these states may determine its function. We examined the structural elements that modulate apoA-IV lipid binding by producing a series of deletion mutants and determining their ability to interact with phospholipid liposomes. We found that the deletion of residues 333-343 strongly increased the lipid association rate versus native apoA-IV. Additional mutagenesis revealed that two phenylalanine residues at positions 334 and 335 mediated this lipid binding inhibitory effect. We also observed that residues 11-20 in the N terminus were required for the enhanced lipid affinity induced by deletion of the C-terminal sequence. We propose a structural model in which these sequences can modulate the conformation and lipid affinity of apoA-IV.


Colonic infarction and pancreatitis: a case report.
A case of almost total colonic infarction secondary to pancreatitis is described. This appears to be a very rare complication of acute pancreatitis and is a result of mesenteric venous thrombosis secondary to the acute inflammatory process. The clue to the diagnosis was the passage of bright blood per rectum and a rapid deterioration in the condition of a patient with severe pancreatitis. Subtotal colectomy with ileostomy and mucous fistula formation was the treatment of choice. Ileosigmoid anastomosis was performed six months later.


Update on acquired hypogonadism in men living with HIV: pathogenesis, clinic, and treatment.
Hypogonadism is a frequent finding among men living with HIV (MLWH) and it seems to occur earlier in comparison with the general male population. Although the prevalence of hypogonadism in MLWH has significantly lowered thanks to advancements in medical management, it remains high if compared with age-matched HIV-uninfected men, ranging from 13% to 40% in the age group of 20-60 years. Signs and symptoms of low serum testosterone (T) in MLWH are cause of concern since they are non-specific, of mild-to-moderate degree, and often overlapping with those of infection per se. For these reasons, hypogonadism can be underestimated in the absence of targeted laboratory blood examinations. With regard to the etiological factors involved in the T decrease, emerging evidence has suggested the functional nature of hypogonadism in MLWH, pointing out the mutual relationship between sex steroids, health status, comorbidities, and HIV-related factors. In agreement with this hypothesis, a therapeutic approach aiming at improving or reversing concomitant diseases through lifestyle changes (e.g. physical activity) rather than pharmacological T treatment should be theoretically considered. However, considering both patient's barriers to lifestyle changes to be maintained overtime and the lack of evidence-based data on the efficacy of lifestyle changes in normalizing serum T in MLWH, T therapy remains an option when other non-pharmacological interventions are ineffective as well as for all other functional forms of hypogonadism. From this perspective, the traditional therapeutic management of male hypogonadism in MLWH, especially the role of T supplementation, should be revised in the light of the probable functional nature of hypogonadism by considering a good balance between benefits and harmful. This narrative review presents an overview of current knowledge on hypogonadism in MLWH, deepening the factors driving and taking part in T decrease, providing advice for the clinical approach, and underlining the importance of individualized treatment aiming at optimizing non-gonadal comorbidities and thus avoiding over-, or even unnecessary, treatment with T.


Further mapping of quantitative trait loci for female sterility in wheat (Triticum aestivum L.).
Epistasis underlying fertility plays an important role in crop breeding. Although a new female sterile mutant in wheat, XND126, has been identified and a major quantitative trait locus (QTL), taf1, for the female sterility has been mapped, the genetic architecture of the female sterility needs to be further addressed. To identify the interaction involving the gene(s) controlling the female sterility, an investigation was carried out for the seed setting ratio in an F2 population derived from the cross between XND126 and Gaocheng 8901. Among 1250 simple sequence repeat (SSR) primer pairs in the whole genome, a total of 21 markers, obtained by recessive class approach, along with other ten tightly linked markers on reference maps in wheat, were used to survey 243 F2 individuals. As a result, 28 markers were mapped into five genetic linkage groups. The performance for female sterility for each F2 individual was evaluated simultaneously at the Urumqi and Huai'an experimental stations in 2006-2007. The two phenotypic datasets along with marker information were jointly analysed in the detection of QTL using penalized maximum likelihood approach. A total of six QTLs, including two main-effect QTLs, three epistatic QTLs and one environmental interaction and accounting for 0.67-24.55% of the total phenotypic variance, were identified. All estimated effects accounted for 53.26% of the total phenotypic variation. The taf1 detected in previous study was also located on the same marker interval on chromosome 2DS. These results enrich our understanding of the genetic basis of the female sterility.


Courting disaster: How diversification rate affects fitness under risk.
Life is full of risk. To deal with this uncertainty, many organisms have evolved bet-hedging strategies that spread risk through phenotypic diversification. These rates of diversification can vary by orders of magnitude in different species. Here we examine how key characteristics of risk and organismal ecology affect the fitness consequences of variation in diversification rate. We find that rapid diversification is strongly favored when the risk faced has a wide spatial extent, with a single disaster affecting a large fraction of the population. This advantage is especially great in small populations subject to frequent disaster. In contrast, when risk is correlated through time, slow diversification is favored because it allows adaptive tracking of disasters that tend to occur in series. Naturally evolved diversification mechanisms in diverse organisms facing a broad array of environmental risks largely support these results. The theory presented in this article provides a testable ecological hypothesis to explain the prevalence of slow stochastic switching among microbes and rapid, within-clutch diversification strategies among plants and animals.


Medical and surgical treatment of seronegative spondyloarthropathies.
Advances in the treatment of the seronegative spondyloarthropathies are reviewed here. The search for effective disease-modifying agents in this group of disorders has continued. Recent attention has focused primarily on sulfasalazine and different immunosuppressive agents. Sulfasalazine has been evaluated by several groups of investigators in ankylosing spondylitis and psoriatic arthritis. Results have been variable, but data suggest that sulfasalazine is less effective for spinal disease than for peripheral joint involvement. Preliminary studies have shown that cyclosporine and other immunosuppressive agents are beneficial in patients with psoriasis and Behçet's disease. Azathioprine appears to be highly effective in Behçet's disease.


Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes.
The impact of disease burden on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (SCT) has not been well defined. Data from several retrospective series suggest that overt leukemia at the time of transplant increases the risk of relapse. We reviewed the outcomes of 68 consecutive adults with AML (n=60) or myelodysplastic syndromes (MDS) (n=8) who received an allogeneic SCT at the University of Chicago between May 1986 and October 2002 to confirm the importance of currently recognized risk factors for overall survival (OS) and progression-free survival (PFS). In addition, we wanted to determine whether quantification of residual disease by blast percentage or cytogenetic abnormalities at the time of SCT was correlated with outcome. AML subtypes based on the FAB classification were as follows: M0=9, M1=9, M2=16, M3=2, M4=16, M5=3, M6=5. Cytogenetic analysis was available from 52 patients. Using standard morphologic criteria, 34 patients were in complete remission (CR) and 34 had visible leukemia present. The majority of donors were HLA-identical siblings (n=55). In all, 56 patients received myeloablative conditioning regimens and 12 received a reduced-intensity, fludarabine-based conditioning regimen. OS and PFS times were 7.1 months (95% CI, 4.8-10.4) and 5.1 months (95% CI, 3.2-7.8), respectively. Median follow-up from SCT was 4.6 years (range, 0.6-17.0) for survivors. In multivariate analysis, the following factors were found to be associated with worse survival: (1) increased percentage of blasts in the bone marrow at the time of SCT, (2) presence of acute graft-versus-host disease, (3) mismatched donor, (4) Zubrod performance score of >/=2, and (5) age >/=45 years. We also found a trend towards improved outcome among patients in cytogenetic remission as compared to those who had residual cytogenetic abnormalities and those in overt relapse. These data support an association between pre-transplant disease burden and poor outcome after SCT.


Ion channels in urinary bladder.
Urinary epithelia separate urine from interstitial fluid. In the mammal, this tight epithelium has a limited transport capacity but is capable of moving sodium from urine to blood through an aldosterone-sensitive cellular pathway. In lower vertebrates, absorption of ions and water from the urine can contribute significantly to fluid and electrolyte homeostasis. Transepithelial ion transport and maintenance of cellular composition are interdependent, requiring a balance between movements across the apical and basolateral plasma membranes through a variety of pathways including electrodiffusion through ion channels. A variety of such channels has been identified in urinary epithelia. Apical membranes contain amiloride-sensitive, highly selective sodium channels of low conductance (approximately 5-10 pS). There is evidence that in mammalian bladders trypsin-like enzymes in the urine continually degrade these channels, decrease in cation selectivity being followed by loss of the channels from the membrane. New channels stored in the cytoplasm appear to provide a source for replenishment of the membrane. Other channels of higher conductance and lower selectivity have also been described in both mammalian and amphibian bladders, but their physiological significance remains to be established. Basolateral membranes contain potassium channels. In the mammalian bladder, in which chloride appears to be distributed at electrochemical equilibrium, chloride conductance exceeds potassium conductance and patch clamp studies have revealed a chloride channel of conductance approximately 60 pS detectable immediately on patch excision and active at normal membrane potentials. In the amphibian bladder, a variety of findings indicates the presence of a basolateral membrane chloride conductance, but patch clamp data are not yet available.


Role of AMP-activated protein kinase in the regulation of gene transcription.
AMP-activated protein kinase (AMPK) is a regulator of cellular metabolism in response to changes in the energy status of the cells. AMPK was known to shut down energy-consuming pathways in response to a fall in the ATP/AMP ratio by phosphorylating key enzymes of intermediate metabolism. Here we will discuss the recent evidence implicating AMPK in the regulation of gene expression in mammals, mainly in the liver and in the pancreatic beta-cells.


Procurement of bone graft from the iliac crest. An operative approach with decreased morbidity.
We compared the donor site morbidity in fifty-seven consecutive patients in whom a bone graft had been procured from the iliac crest through an incision parallel to the superior cluneal nerves and perpendicular to the posterior iliac crest (the study group) with that in fifty-three consecutive patients in whom the graft had been procured through an oblique incision parallel to the posterior iliac crest (the control group). Numbness, tenderness, and pain at the donor site one and six months postoperatively were assessed by means of an interview with the patient and a review of the records. The prevalence of symptoms in the control group was greater than that in the study group. At one month, thirty-nine patients (74 per cent) in the control group had numbness, compared with twenty-five (44 per cent) in the study group (p = 0.001). At six months, thirty-one patients (58 per cent) in the control group had numbness, compared with fourteen (25 per cent) in the study group (p = 0.0002). Thirty-six patients (68 per cent) in the control group and twenty-four (42 per cent) in the study group had tenderness over the incision at one month (p = 0.005), and twenty-seven (51 per cent) and eleven (19 per cent), respectively, had tenderness at six months (p = 0.0003). Forty patients (75 per cent) in the control group and forty-six patients (81 per cent) in the study group had deep pain in the region of the iliac crest at one month, compared with thirty-two (60 per cent) and thirty-one (54 per cent), respectively, at six months. The mean analog score for pain at the donor site was 7 of 10 points in the control group and 6 points in the study group (p = 0.001) at one month and 3 and 2 points, respectively, at six months (p = 0.001).


Use of recombinant bovine alpha 1 interferon in reducing respiratory disease induced by bovine herpesvirus type 1.
Intranasal or intramuscular treatment of calves with recombinant bovine alpha 1 interferon before challenge with bovine herpesvirus type 1 and Pasteurella haemolytica reduced clinical signs, number of sick days, lung lesions, and weight loss. The effective dose was determined to be relatively broad within the range of 1 to 50 mg per animal. No adverse effects were observed even at high doses of interferon (50 mg per animal). Administration before virus infection was more effective than administration at the same time as virus infection. Although interferon administration had dramatic effects on the survival of animals, it did not have much effect on virus secretion in the upper respiratory tract. Therefore, the mechanism by which interferon reduces the susceptibility of animals to viral-bacterial synergy was postulated to be via its immunomodulatory effects.


Harnessing a nanostructured fluorescence energy transfer sensor for quick detection of extremely small amounts of glucose.
Fluorescence technique is one of the major solutions for achieving the continuous and noninvasive glucose sensor for diabetes. In this article, a highly sensitive nanostructured sensor is developed to detect extremely small amounts of aqueous glucose by applying fluorescence energy transfer (FRET). A one-pot method is applied to produce the dextran-fluorescein isothiocyanate (FITC)-conjugating mesoporous silica nanoparticles (MSNs), which afterward interact with the tetramethylrhodamine isothiocyanate (TRITC)-labeled concanavalin A (Con A) to form the FRET nanoparticles (FITC-dextran-Con A-TRITC@MSNs). The nanostructured glucose sensor is then formed via the self-assembly of the FRET nanoparticles on a transparent, flexible, and biocompatible substrate, e.g., poly(dimethylsiloxane). Our results indicate the diameter of the MSNs is 60 ± 5 nm. The difference in the images before and after adding 20 μl of glucose (0.10 mmol/liter) on the FRET sensor can be detected in less than 2 min by the laser confocal laser scanning microscope. The correlation between the ratio of fluorescence intensity, I(donor)/I(acceptor), of the FRET sensor and the concentration of aqueous glucose in the range of 0.04-4 mmol/liter has been investigated; a linear relationship is found. Furthermore, the durability of the nanostructured FRET sensor is evaluated for 5 days. In addition, the recorded images can be converted to digital images by obtaining the pixels from the resulting matrix using Matlab image processing functions. We have also studied the in vitro cytotoxicity of the device. The nanostructured FRET sensor may provide an alternative method to help patients manage the disease continuously.


[Psycho-behavioral disorders in geriatric institution].
Residents in geriatric institutions are progressively older, and they increasingly present psycho-behavioural disorders that affect the function of these institutions. Only after failure of classical medical investigation based on the observed symptoms and seeking a well-defined syndrome and treatment are these disorders attributed to progressive intellectual deterioration which escapes all classical "technical" medical efforts. Drug treatment thus becomes accessory and the disorders must be viewed as complex interactions between the subject and his institutional and familial circles. These interactions are highly pathogenic and feed the symptomatology, aggravating the disorders and producing new symptoms. For this reason, management must be adaptative, aiming at the best possible equilibrium of the subject in the institution. It should also be fully encompassing, engaging the whole of the actors within the institution. The objective can only be attained by a team equipped with gereologic knowledge, used to interdisciplinary work and constantly seeking an explicit institutional aim, taking into account all the required medical, psychological, social, familial, judicial and ethic factors.


Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls.
Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whether concurrent oral administration of meloxicam (1 mg/kg BW) would alter these responses. On d -1, crossbred bull calves ( = 30; initial BW = 227.4 ± 10.3 kg) were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices, placed into individual stanchions, and randomly assigned to 1 of 3 treatments. Treatment application occurred at h 0 and consisted of 1) intact bull calves treated with sham castration (CON), 2) bulls surgically castrated without meloxicam administration (CAS), and 3) bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL). Blood samples were collected at 0.5-h intervals from h -2 to 4, 1.0-h intervals from h 4 to 8, and 12-h intervals from h 12 to 72. Serum was analyzed for cortisol and haptoglobin (Hp) concentrations using ELISA. Whole blood was analyzed for complete blood counts at -2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, and RT was recorded in 5-min intervals. Postcastration RT was greatest for MEL (39.04), intermediate for CAS (38.99), and least for CON (38.93°C; ≤ 0.01). Serum cortisol was increased ( < 0.001) for CAS (12.3) and MEL (11.3) compared with CON (6.7 ng/mL) during the postcastration period. At 0.5 and 1.5 h, cortisol concentration was greater in CAS and MEL than CON, whereas at 2 and 2.5 h, cortisol concentration was greatest for CAS, intermediate for MEL, and least for CON (treatment × time, < 0.001). Total white blood cell ( ≤ 0.04), lymphocyte ( ≤ 0.02), and monocyte ( ≤ 0.002) counts were greatest for CAS, intermediate for MEL, and least for CON. Administration of MEL reduced ( ≤ 0.002) eosinophil counts during the postcastration period when compared with CON and CAS. The change in serum Hp, relative to baseline values, was reduced for MEL at 36 ( < 0.01) and 60 h ( ≤ 0.03), and the overall Hp concentration was least for MEL ( < 0.001). Oral administration of meloxicam at the time of castration reduced the acute inflammatory response in castrates, as evidenced by a reduction in Hp and certain leukocyte concentrations; it also caused a delayed increase in RT. Further research is needed to determine if this reduced acute inflammatory response would equate to improved health and/or performance after castration.


Microstructure of bentonite in iron ore green pellets.
Sodium-activated calcium bentonite is used as a binder in iron ore pellets and is known to increase strength of both wet and dry iron ore green pellets. In this article, the microstructure of bentonite in magnetite pellets is revealed for the first time using scanning electron microscopy. The microstructure of bentonite in wet and dry iron ore pellets, as well as in distilled water, was imaged by various imaging techniques (e.g., imaging at low voltage with monochromatic and decelerated beam or low loss backscattered electrons) and cryogenic methods (i.e., high pressure freezing and plunge freezing in liquid ethane). In wet iron ore green pellets, clay tactoids (stacks of parallel primary clay platelets) were very well dispersed and formed a voluminous network occupying the space available between mineral particles. When the pellet was dried, bentonite was drawn to the contact points between the particles and formed solid bridges, which impart strength to the solid compact.


A survival study of cervical cancer in Chennai, India.
A total of 4304 cervical cancer cases registered during 1982-89 in Chennai registry, India, were analyzed. Relative survival at 1, 3 and 5 years were 90%, 72% and 60% respectively. Age at diagnosis and extent of disease emerged as statistically significant prognostic factors (p<0.001). Five-fold higher risk of death was seen among those above 64 years vs. <45 years and those with distant metastasis vs. localized disease at diagnosis. Cancer control programs focusing on health education would motivate women to attend hospital at an early stage of disease for better survival.