Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra.
Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no association between cytokine release and bone mass or loss assessed over 2 yrs. The only exception was a weak estrogen-independent correlation between basal IL-1ra secretion and bone loss (r = -0.21, p < 0.05). Flow cytometry did not confirm a relationship between CD4/CD8 T-cell ratios and bone density or loss, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p < 0.01) similar to that found in patients with established osteoporosis, indicating that these adherent mononuclear cells may be important in the pathophysiology of post-menopausal bone loss. The possibility that IL-1ra acts as an independent bone-sparing factor unrelated to estrogen withdrawal warrants further investigation. In conclusion, ERT maintains bone without affecting the release of the IL-1 family of cytokines in whole blood cultures.


Vaccine-associated "wild-type" measles.
Measles is the most contagious of the childhood exanthems and is the leading cause of vaccine-preventable deaths in children, mostly in developing countries. The prodromal stage, consisting of high fever and the triad of cough, coryza, and conjunctivitis, is followed by a caudal progressing rash over a period of 2 to 3 days. With a worldwide vaccination program in place, mortality and morbidity have decreased substantially. Receipt of the live attenuated vaccine generally causes no or only mild side effects such as a low-grade fever and a subtle rash. We report a 1-year-old boy who, 10 days after vaccination, developed vaccine measles which was clinically indistinguishable from the natural disease. Vaccine virus was detected by polymerase chain reaction in the patient's nasopharyngeal secretions.


Value of teamwork.
I recently attended a national consensus conference to take part in a debate on advanced nursing practice.


Tissue expression and the host's immunological recognition of a Rhipicephalus microplus paramyosin.
Rhipicephalus microplus is a parasite that causes economic losses in cattle herds, and immunological control is the most promising alternative to replace chemical control. The muscular protein paramyosin has been additionally found in non-muscle tissues and characterized as presenting activities that enable the evasion of the host's immune system in various parasites. This report investigated the recognition level of paramyosin by sera of infested bovines, its expression in tissues, organs and different life stages of R. microplus. ELISA analyses showed that paramyosin and salivary gland extract were recognized by infested Bos taurus and B. indicus sera. Paramyosin gene expression was evaluated in egg, larvae, adult male, and several tissues of partially- and fully-engorged females by qRT-PCR, showing the highest expression levels in fat body. These results show that R. microplus paramyosin is immunologically recognized during the tick infestation and together with the high transcription rate found in organs that do not present a highly developed musculature, further suggests that it may possess additional, non-muscle functions in the tick-bovine relationship.


Normal recovery of the stratum corneum barrier function following damage induced by tape stripping in patients with atopic dermatitis.
Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC), after its complete removal by tape stripping, in patients with AD and age-matched healthy control subjects. On the normal-looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.


Barring intervention? Lesbian and gay bars as an underutilized venue for tobacco interventions.
Lesbian, gay, bisexual, and transgender (LGBT) communities are at high risk for tobacco use. While LGBT communities have historically considered bars to be safe places to socialize and congregate, these spaces are often tobacco-friendly environments and may have potential as sites for much needed intervention. Only a few public health interventions have attempted to work through bars and clubs to decrease tobacco use in the LGBT populations. Evidence from HIV prevention suggests some potential interventions in bars, and the tobacco industry has worked extensively (and successfully) to utilize bars in marketing efforts. Lesbian and gay bars are underutilized in tobacco control, suggesting missed avenues for chronic disease prevention programs. Researchers and communities should continue to recognize the importance of clean indoor air laws covering bars and develop additional strategies for reaching LGBT populations with disparities.


Fluoride varnish was effective at reducing caries on high caries risk school children in rural Brazil.
Placebo controlled randomised controlled trial (RCT). Recruited children were randomly assigned to either a treatment (5% NaF varnish, n = 198) or a control group (placebo, n = 181). Data on oral health habits and socio-demographic characteristics was collected from the children by trained interviewers. Diet information was collected using a seven day food frequency diary. Caries was assessed using the International Caries Detection and Assessment System (ICDAS). The main outcome was decayed and filled surfaces (DFS) increment at 12 months. Two hundred and ten (55.4%) children having one or two applications of fluoride varnish or placebo were available for follow-up at 12 months. At the baseline examination, the children in the treatment and control groups presented with on average 6.2 and 5.6 DFS, respectively (P < 0.001). At 12 months, the children in the varnish group showed significantly lower DFS increments than did children in the control group (10.8 versus 13.3; P < 0.007), with a preventive fraction (PF) of 40% (95% CI: 34.3-45.7%; P < 0.0001). The results of this study suggest that applications of 5% NaF varnish can be recommended as a public health measure for reducing caries incidence in this high-caries-risk population.


Manipulating the quantum interference effect and magnetotransport of ZnO nanowires through interfacial doping.
We carefully prepared interfacial Al-doped (IAD) and interfacial natively-doped (IND) ZnO nanowires (NWs) by introducing atomic-layer interfacial Δ-doping between the two steps of CVD growth. Variable-temperature electron transport as well as magnetotransport behaviours of these NWs were systematically investigated. By virtue of the unique architecture and the quality-guaranteed growth technique, a series of quantum interference effects were clearly observed in the IAD ZnO NWs, including weak localization, universal conductance fluctuation and Altshuler-Aronov-Spivak oscillations. The phase-coherence length (Lφ) of electrons exceeds 100 nm in the IAD ZnO NWs, much longer than those in the IND ones and most conventionally doped ZnO NWs. This ability to efficiently manipulate a variety of quantum interference effects in ZnO NWs is very desirable for applications in nano-optoelectronics, nano- & quantum-electronics and solid-state quantum computing.


[Recovery of 3D structure from motion and its statistical efficiency].
In order to investigate characteristics of the "structure from motion" in noise, we compared performances of recovering a three-dimensional structure from motion (3D condition) with those of recovering a two-dimensional structure (2D condition). In addition, we adopted a statistical efficiency approach to analyze the results. We conducted two experiments where we presented to observers a pair of three dots corresponding to three apexes of triangles rotating around an axis projected onto the fronto-parallel plane. A gaussian noise was added to the area of each triangle for each stimulus frame. Observers were required to discriminate areas of two triangles perceived with moving dots. Main results were as follows: (a) Significant difference was found between the efficiencies for 3D condition and 2D condition. We obtained about 50% or less recovery (i.e., a ratio of the 3D efficiency to the 2D one) in Experiment 2. (b) When we removed the constraints, the human efficiency and the percent recovery decreased dramatically.


Analytical error and interference in immunoassay: minimizing risk.
Although generally robust, immunoassays remain vulnerable to occasional analytical errors that may have serious implications for patient care. Sporadic errors that occur as a result of properties of the specimen are particularly difficult to detect. They may be due to the presence of cross-reacting substances, antianalyte antibodies or antireagent antibodies, all of which may lead to erroneously high or low results. Low results may be observed for tumour markers due to high-dose hooking in the presence of very high analyte concentrations. Erroneous results can occur unexpectedly with any specimen and there is no practical means of identifying specimens likely to cause problems in immunoassays. The possibility of interference should always be considered when results do not appear to be in accord with the clinical picture. Errors can occur in even the best-managed laboratories and their early investigation is always desirable. If there is any doubt whatsoever about a result, clinical staff should be encouraged to contact the laboratory. Investigations for possible interference that can be undertaken in most laboratories include testing for linearity on dilution, recovery experiments, treatment with heterophilic blocking tubes and confirmation using a different method. It may be desirable to consult specialist laboratories if more complex studies are necessary. Informing clinical and laboratory staff of the ever-present possibility of unexpected interference, ensuring brief clinical details are available to laboratory staff, and above all facilitating excellent communication between laboratory and clinical staff are key to minimizing the risk of clinical mismanagement due to unsuspected interference.


Startle reveals independent preparation and initiation of triphasic EMG burst components in targeted ballistic movements.
Muscles involved in rapid, targeted movements about a single joint often display a triphasic [agonist (AG1)-antagonist (ANT)-agonist (AG2)] electromyographic (EMG) pattern. Early work using movement perturbations suggested that for short movements, the entire EMG pattern was prepared and initiated in advance (Wadman WJ, Dernier van der Gon JJ, Geuze RH, Mol CR. J Hum Mov Stud 5: 3-17, 1979), whereas more recent transcranial magnetic stimulation evidence indicates that the ANT may be programmed separately (MacKinnon CD, Rothwell JC. J Physiol 528: 633-645, 2000) with execution of the bursts occurring serially (Irlbacher K, Voss M, Meyer BU, Rothwell JC. J Physiol 574: 917-928, 2006). The purpose of the current study was to investigate the generation of triphasic EMG bursts for movements of different amplitudes. In experiment 1, participants performed rapid elbow extension movements to 20° and 60° targets, and on some trials, a startling acoustic stimulus (SAS), which is thought to trigger prepared motor commands at short latency, was delivered at the onset of AG1. For short movements, this perturbation elicited ANT and AG2 early, suggesting the agonist and antagonist bursts may have been programmed independently. In contrast, the same manipulation did not disrupt EMG timing parameters for the long movements, raising the possibility that ANT and AG2 were not fully programmed in advance of movement onset. In experiment 2, an SAS was delivered later in the movement, which produced early onset of both ANT and AG2. We propose that the triphasic pattern is executed serially but believe the trigger signal for initiating the ANT burst occurs not in relation to the AG1 burst, but rather in close temporal proximity to the expected onset of ANT.


Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal men.
Studies of sleep influences on human pharyngeal and other respiratory muscles suggest that the activity of these muscles may be affected by non-rapid-eye-movement (NREM) sleep in a nonuniform manner. This variable sleep response may relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic) and peripheral events occurring in the airway. Furthermore, the ability of these muscles to respond to respiratory stimuli during NREM sleep may also differ. To systematically investigate the effect of NREM sleep on respiratory muscle activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s) during wakefulness and NREM sleep. Seven normal male subjects were studied on a single night with intramuscular electrodes placed in the TP and GG and surface electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving time average electromyograph (EMG) of the above four muscles were continuously recorded. The EMG of both tonic muscles fell significantly (P less than 0.05) during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/- 0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5; stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both inspiratory phasic muscles (GG and D) was well maintained.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of modified atmosphere treatment on post-harvest reactive oxygen metabolism of pomegranate peels.
Modified atmosphere storage can regulate the reactive oxygen metabolism of fruits and vegetables, reduce the accumulation of hazardous free radicals, and mitigate the peroxidation degree of fruit membrane lipids. In this study, different gas matching ratios were adopted for the modified atmosphere treatment of pomegranate fruits. Up to 120 d of storage, compared with the control treatment, the H2O2 and malonaldehyde (MDA) contents in treatment 2 decreased by 8.88% and 18.28%, respectively, when the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbic acid peroxidase (APX) in treatment 2 increased by 21.44%, 117.38% and 114.95%, the ascorbic acid (ASA) and glutathione (GSH) contents in treatment 2 also increased by 116.83% and 50%, these results showed that treatment 2 (6.0% O2, 6.0% CO2) could effectively regulate various indexes of the reactive oxygen metabolism of pomegranate peels, maintain the normal physiological actions of the fruits, and postpone the ripening and senescence of histocytes. Under treatment 4 (10.0% O2, 10.0% CO2), H2O2 contents in the pomegranate peel significantly increased, and the activities of SOD, CAT and APX significantly reduced. ASA and GSH were degraded, the MDA content abruptly increased, the membrane lipid peroxidation accelerated, and the cytomembrane structure was destroyed.


Functional Polymorphisms of CTLA4 Associated with Aggressive Periodontitis in the Chinese Han Population.
CTLA4 has been identified functioning as a protein receptor which functions as an immune checkpoint, downregulating the immune system. Susceptibility to aggressive periodontitis (AgP) is influenced by gene polymorphisms related to the immune response. In this study, we focused on SNPs in the 3'-UTR of CTLA4 among Chinese AgP patients, and investigated any further relationships between the SNPs and miRNAs. This case-control study included 120 AgP patients and 150 healthy controls. Genotyping was used to detect allele distribution. Cell transfection and the dual luciferase reporter assay were performed to investigate the potential functions of SNPs located in the 3'UTR of CTLA4. The data show that patients with a history of smoking were more susceptible compared to controls, exhibiting deeper probing depth, greater attachment loss and more sites of bleeding on probing. The results of genotyping analysis revealed that individuals with the GA and AA genotypes, and with the A carrier had a decreased risk (P = 0.015, P = 0.03). Furthermore, patients with the G allele might be regulated by miR-105, which caused a down-regulation of CTLA4. The carriers of the GG genotype exhibited the worst results of attachment loss and bleeding on probing. These findings show that rs56102377 in the 3'-UTR of CTLA4 may act as a protective factor by disrupting the regulatory role of miR-105 in CTLA4 expression. Thus, our study highlighted a potential role of these polymorphisms as genetic susceptibility biomarkers of periodontitis in Chinese Han populations.


Repetitive chemoembolization of hypovascular liver metastases from the most common primary sites.
To evaluate tumor response in patients with hypovascular liver metastases from the most common primary sites treated with chemoembolization. Chemoembolization was performed in 190 patients (five groups) who had hypovascular liver metastases from the colon (n = 66), breast (n = 40), uveal malignant melanoma (n = 20), pancreas (n = 48) and stomach (n = 16). Surgical resection of primary sites had been performed for all included patients. Tumor response, survival statistics from the first chemoembolization using Kaplan-Meier method and progression rate of embolized lesions were evaluated by analysis of variance with Tukey's post hoc test. Multiple comparison between the groups showed no statistical significant difference in local tumor response (H: 9.23; p > 0.05). Survival indices of the patients, including survival rate, progression-free survival rate, median survival time and time to progression, demonstrated significant difference between the groups during the follow-up period (H: 9.7; p = 0.045). The progression rate of treated liver metastases from colon, breast, uvea, pancreas and stomach were 16.6, 17.5, 30.0, 25.0 and 32.0%, respectively (p = 0.002). Hypovascular liver metastases treated with chemoembolization may demonstrate equal local response, but are significantly different in rate of progression and survival.


Consequences of intravascular catheter sepsis.
Intravascular (IV) catheter sepsis is a widely recognized complication of IV therapy or monitoring, but little emphasis has been placed on the morbidity and cost associated with this infection. To assess the consequences of IV catheter sepsis, we examined the medical records of 94 patients with 102 episodes of IV catheter sepsis due to percutaneously inserted catheters. Major complications occurred in 33 (32%) of the episodes and included septic shock (12 episodes), sustained sepsis (12), suppurative thrombophlebitis (7), metastatic infection (5), endocarditis (2), and arteritis (2). One patient died due to sepsis, and hospital stay was clearly prolonged in 15 episodes. The risk of major complications was highest in episodes of IV catheter sepsis caused by Candida, Pseudomonas aeruginosa, Staphylococcus aureus, or multiple pathogens, and the most severe complications were usually caused by S. aureus. The hospital cost of IV catheter sepsis was assessed by reviewing medical and billing records to identify extra medical care and then multiplying charges for that care by the appropriate cost-to-charge ratio. The average cost per episode, adjusted to 1991 dollars, was $3,707 for all episodes and $6,064 for episodes caused by S. aureus. The morbidity and cost associated with IV catheter sepsis warrant substantial efforts to minimize the incidence of this complication and especially to prevent cases due to S. aureus.


Some artefacts of the approaches with the discretization in near-field optics calculations.
This article is devoted to an observation artefact arising in near-field optical calculations by methods with the discretization of a scattering object and the substitution of separated dipoles instead of discretizing meshes. It is discussed that such an artificial discretization gives within the object a non-monotonously changing field on the scale of the discretizing mesh size, which propagates from the object to a distance of the same order of magnitude as the mesh size in contrast to the real situation where such a non-monotonously changing fields exist on the scale of a real atomic lattice. If such a non-monotonously changing field exists in the observation plane where the picture is calculated, the choice of the observation points can change the obtained picture remarkably.


Unique structural features that influence neutrophil emigration into the lung.
Neutrophil emigration in the lung differs substantially from that in systemic vascular beds where extravasation occurs primarily through postcapillary venules. Migration into the alveolus occurs directly from alveolar capillaries and appears to progress through a sequence of steps uniquely influenced by the cellular anatomy and organization of the alveolar wall. The cascade of adhesive and stimulatory events so critical to the extravasation of neutrophils from postcapillary venules in many tissues is not evident in this setting. Compelling evidence exists for unique cascades of biophysical, adhesive, stimulatory, and guidance factors that arrest neutrophils in the alveolar capillary bed and direct their movement through the endothelium, interstitial space, and alveolar epithelium. A prominent path accessible to the neutrophil appears to be determined by the structural interactions of endothelial cells, interstitial fibroblasts, as well as type I and type II alveolar epithelial cells.


CCN3/Nephroblastoma Overexpressed Is a Functional Mediator of Prostate Cancer Bone Metastasis That Is Associated with Poor Patient Prognosis.
Prostate cancer (PC) commonly metastasizes to the bone, resulting in pathologic fractures and poor prognosis. CCN3/nephroblastoma overexpressed is a secreted protein with a known role in promoting breast cancer metastasis to bone. However, in PC, CCN3 has been ascribed conflicting roles; some studies suggest that CCN3 promotes PC metastasis, whereas others argue a tumor suppressor role for CCN3 in this disease. Indeed, in the latter context, CCN3 has been shown to sequester the androgen receptor (AR) and suppress AR signaling. In the present study, we demonstrate that CCN3 functions as a bone-metastatic mediator, which is dependent on its C-terminal domain for this function. Analysis of tissue microarrays comprising >1500 primary PC patient radical prostatectomy specimens reveals that CCN3 expression correlates with aggressive disease and is negatively correlated with the expression of prostate-specific antigen, a marker of AR signaling. Together, these findings point to CCN3 as a biomarker to predict PC aggressiveness while providing clarity on its role as a functional mediator of PC bone metastasis.


Cholelithiasis - always infected?
This study aims to present results regarding the presence and identification of bacterial strains found in bile and gallstones located in the gallbladder and bile ducts in patients operated on due to cholelithiasis. Bacterial culture was evaluated in 92 patients. There were 54 women (59%) and 38 men (41%) who underwent surgery on account of cholelithiasis and /or gallstones in bile ducts between 2013 and 2014. Bile and gallstone samples were cultured intraoperatively for bacteria; bacterial strains were identified, and their sensitivity to antibiotics was determined. Molecular methods (NGS and Sanger method) were used to separate bacterial strains in one of the gallbladder stones and the results were compared with bacterial strains grown from the bile. Bile cultures were positive in 46 patients that is, 50% of the study group. The following bacteria strains were grown: Enterococcus spp. (44%), Escherichia coli (37%) and Klebsiella spp. (35%). Candidiasis accompanied by bacterial infection was detected in 7 patients (15%). Molecular testing of gallstones revealed DNA of Enterococcus spp., Escherichia spp., Streptococcus spp. and Clostridium spp. In the bile culture of the same patient Enterococcus spp. (avium and faecalis) was detected. Conclusion 1. More than one pathogen was grown on samples obtained from 31 patients (70%) with bile infection. 2. The most common pathogens include Enterococcus spp., Escherichia coli and Klebsiella spp. 3. Bacterial infections are often accompanied by a fungal infection (Candida albicans) 4. Bacterial strains grown from a gallstone sample partially corresponded with strains identified in the bile of the same patient.


Day-patient treatment after short inpatient care versus continued inpatient treatment in adolescents with anorexia nervosa (ANDI): a multicentre, randomised, open-label, non-inferiority trial.
In-patient treatment (IP) is the treatment setting of choice for moderately-to-severely ill adolescents with anorexia nervosa, but it is costly, and the risks of relapse and readmissions are high. Day patient treatment (DP) is less expensive and might avoid problems of relapse and readmission by easing the transition from hospital to home. We investigated the safety and efficacy of DP after short inpatient care compared with continued IP. For this multicentre, randomised, open-label, non-inferiority trial, we enrolled female patients (aged 11-18 years) with anorexia nervosa from six centres in Germany. Patients were eligible if they had a body-mass index (BMI) below the tenth percentile and it was their first admission to hospital for anorexia nervosa. We used a computer-generated randomisation sequence to randomly assign patients to continued IP or DP after 3 weeks of inpatient care (1:1; stratified for age and BMI at admission). The treatment programme and treatment intensity in both study groups were identical. The primary outcome was the increase in BMI between the time of admission and a 12-month follow-up adjusted for age and duration of illness (non-inferiority margin of 0·75 kg/m(2)). Analysis was done by modified intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN67783402, and the Deutsches Register Klinischer Studien, number DRKS00000101. Between Feb 2, 2007, to April 27, 2010, we screened 660 patients for eligibility, 172 of whom we randomly allocated to treatment: 85 to IP and 87 to DP. DP was non-inferior to IP with respect to the primary outcome, BMI at the 12-month follow-up (mean difference 0·46 kg/m(2) in favour of DP (95% CI, -0·11 to 1·02; pnon-inferiority<0·0001). The number of treatment-related serious adverse events was similar in both study groups (eight in the IP group, seven in the DP group). Three serious adverse events in the IP group and two in the DP group were related to suicidal ideation; one patient in the DP attempted suicide 3 months after she was discharged. DP after short inpatient care in adolescent patients with non-chronic anorexia nervosa seems no less effective than IP for weight restoration and maintenance during the first year after admission. Thus, DP might be a safe and less costly alternative to IP. Our results justify the broad implementation of this approach. German Ministry for Education and Research.


Cross-sectional echocardiography in assessing the severity of valvular aortic stenosis.
Real-time, cross-sectional echocardiograms were recorded in 28 consecutive adult patients with valvular aortic stenosis using a high resolution, mechanical sector scanner. Using the cross-sectional technique, the aortic valve orifice diameter was recorded in each of the 28 patients. With M-mode echocardiographic examination of these same patients, this value could be estimated in only 21 of these 28 patients (75%). The maximum aortic valve diameter recorded during the cross-sectional study averaged 7.9 +/- 1.8 mm (range 4-11 mm) in 15 patients with severe aortic stenosis; 11.6 +/- 2.3 mm (range 9-15 mm) in five patients with moderate aortic stenosis; 16.9 +/- 2.0 mm (range 14-20 mm) in eight patients with mild aortic stenosis; and 20.5 +/- 2.8 mm (range 15-26 mm) in 25 patients with no evidence of aortic valve disease. Comparing the means of these groups yielded the following: severe vs moderate P less than 0.005; moderate vs mild P less than 0.001; and mild vs normal P less than 0.001. Although there was some overlap between the individual groups, a clear separation existed between patients with severe and mild aortic stenosis. In addition, the group of patients in whom surgical intervention was recommended was also separated from the other subjects. When the aortic valve orifice was recorded using the M-mode technique, there was also a good correlation with the severity of the stenosis; however, the tendency of the M-mode study to overestimate severity in individual patients with calcific aortic stenosis and to underestimate severity in congenital aortic stenosis was again demonstrated. This study suggests that real-time, high resolution, cross-sectional echocardiography should be valuable in the noninvasive assessment of patients with aortic stenosis.


Serodiscussion, Perceived Seroconcordance, and Sexual Risk Behaviors Among Dyads of Men Who Have Sex with Men Who Use Geosocial-Networking Smartphone Applications in London.
Serodiscussion-the mutual discussion of HIV statuses between sexual partners-can be viewed as an essential prerequisite for risk-reduction behaviors among men who have sex with men (MSM). The current study aimed to assess the prevalence of serodiscussion with one's most recent sexual partner and its association with sexual behaviors with these partners. Broadcast advertisements were placed on a geosocial-networking smartphone application, encouraging users to complete an online survey. A total of 200 MSM completed the survey. Serodiscussion occurred in 43.5% of dyads, and it was most common in dyads where both partners were reported to be HIV positive, χ2(5) = 60.3, P < .001. Serodiscussion was associated with engagement in both condomless insertive, χ2(1) = 3.847, P = .046, and receptive anal intercourse, χ2(1) = 6.5, P = .011. However, there were no significant differences in how recently a respondent was tested for HIV, representing potentially high-risk scenarios.


Do diurnal cortisol levels mediate the association between sleep disturbances and cognitive impairment?
Previous research found an association between sleep disturbances and cognitive deficits on the one hand, and between increased cortisol levels and poor cognitive performance on the other hand. We hypothesized that cortisol may, at least partially, mediate the link between sleep disturbances and cognitive impairment (CI). We analyzed data from 440 nondemented subjects aged ≥65 years (72.4 ± 4.5 years old, 55.7% women) participating at the population-based CoLaus/PsyCoLaus study, who underwent cognitive evaluation, complete polysomnography and cortisol measures during the day. Subjects with CI (N = 207, 47.05% of the sample) had lower sleep efficiency, less deep sleep (stage N3) and rapid eye movement sleep, and higher apnea/hypopnea index and oxygen desaturation index. After adjustment for possible confounders, oxygen desaturation index (≥4% and ≥6% per hour of sleep) were significantly associated with impaired cognitive performance. The results of Sobel's test for mediation using the regressions between the sleep-related variables and cortisol values, and between the cortisol and the Clinical Dementia Rating score were not significant (all p > 0.05). Our data suggest that sleep-disordered breathing is associated with CI, but that this association is not mediated by increased diurnal cortisol levels.


Development of basic nursing education in China and Hong Kong.
Hong Kong returned to the sovereignty of the People's Republic of China in July 1997. In the past, Hong Kong has been greatly influenced by the British system of nurses' training, which was very different from that in mainland China. As Hong Kong is now a part of China again, there is an increased opportunity for the exchange of experience and ideas among nurse educators. The First China-Hong Kong Nursing Education Conference has provided opportunities for the authors to gain a deeper understanding of the development of nursing education in China and Hong Kong. The authors believe that it is also important for China and Hong Kong to increase networking with the international nursing community. This paper has been written largely based on the information gathered from papers presented in the Conference and the discussion with nurse educators who attended the Conference, together with a review of literature. This paper focuses on comparing the history and present development of basic nursing education in both places. The future direction for the development of nursing education in these two places will also be discussed.


Proceedings for the 5th Asia-Pacific Conference on Disaster Medicine: creating an agenda for action.
Disaster medicine has come to the forefront and has become the focus of interest not only in the medical community, but also in the eyes of the public. The 5th APCDM was convened in Vancouver, Canada, 27-30 September 2000. It brought together over 300 delegates from 32 countries to share their experiences and thoughts regarding disaster events and how to effectively manage them. The conference was devoted to the task of establishing priorities and creating an Agenda for Action. From the discussions, key actions required were defined: COMMUNICATIONS: (1) Identify existing regional telehealth groups and gather lessons to be learned from them; (2) Form a telehealth advisory group to work with regional groups to compile telehealth initiatives, identify international protocols in telehealth already in existence, and solicit feedback before setting international standards; and (3) Increase corporate partnerships in the fields of telehealth and telecommunications, and invite corporations to send delegates to future APCDM meetings. This should be an initiative of the APCDM, the World Association of Disaster and Emergency Medicine (WADEM), or the European Society of Emergency Medicine. EDUCATION AND RESEARCH: (1) Formalize education in disaster medicine and management. The World Health Organization and WADEM should take a leadership role; (2) WADEM is requested to hold a conference with a focus on qualitative research; (3) WHO is requested to continue the provision of international research teams, but to advocate for the development of national disaster research infrastructure; (4) Make research findings and reports available on web sites of such organizations as WHO and PAHO; (5) Develop the translation of research for community utilization. The WHO and PAHO are organizations that are requested to consider this action; and (6) WADEM/APCDM are requested to focus future conferences on applied research. INFORMATION AND DATA: (1) Create an "Information and Data Clearinghouse on Disaster Management" to collect, collate, and disseminate information; (2) Collect data using standardized tools, such as CAR or Hazmat indices; (3) Analyze incentives and disincentives for disaster readiness and establish mechanisms for addressing the obstacles to preparedness; and (4) WADEM is requested to develop a web site providing a resource list of interdisciplinary institutions and response activities, organized by country, topic, and research interests. Links to other pertinent web sites should be provided. INTERDISCIPLINARY DEVELOPMENT: (1) Focus on the interdisciplinary nature of disaster response through more conferences encompassing grassroots efforts and through WADEM publications; (2) Develop and apply a standardized template of Needs Assessment for use by multidisciplinary teams. Team Needs Assessment is essential to determine the following: (a) Local response and international assistance required; (b) Appropriate command system; and (c) Psychosocial impact and support necessary. PSYCHOSOCIAL ASPECTS: (1) Incorporate relief for caregivers into action plans. This should include prime family members who also are caregivers; and (2) Implement measures that give survivors control over the recovery process. RESPONSE MANAGEMENT: (1) Define relationships and roles between governments, military and security personnel, non-governmental organizations (NGOs), and civic groups. Use an international legal framework and liability to reinforce accountability of disaster responders; (2) Establish a more sophisticated use of the media during disasters; (3) Establish standards in key areas. WADEM is requested to write "White Papers" on standards for the following areas: (a) management, (b) health/public health, (c) education/training, (d) psychosocial, and (e) disaster plans; (4) Establish task forces to anticipate and resolve issues around evolving and emerging disasters (e.g., chemical and biological terrorism, landmines, emerging infectious diseases). WADEM was again identified as the vehicle for promoting this action. The responsibility of the next meeting of the Asia-Pacific Conference on Disaster Medicine will be to measure progress made in these areas by assessing how well these collective decisions have been implemented.


Evolving interpretable structure-activity relationship models. 2. Using multiobjective optimization to derive multiple models.
A multiobjective evolutionary algorithm (MOEA) is described for evolving multiple structure-activity relationships (SARs). The SARs are encoded in easy-to-interpret reduced graph queries which describe features that are preferentially present in active compounds compared to inactives. The MOEA addresses a limitation associated with many machine learning methods; that is, the inherent tradeoff that exists in recall and precision which is usually handled by combining the two objectives into a single measure with a consequent loss of control. By simultaneously optimizing recall and precision, the MOEA generates a family of SARs that lie on the precision-recall (PR) curve. The user is then able to select a query with an appropriate balance in the two objectives: for example, a low recall-high precision query may be preferred when establishing the SAR, whereas a high recall-low precision query may be more appropriate in a virtual screening context. Each query on the PR curve aims at capturing the structure-activity information into a single representation, and each can be considered as an alternative (equally valid) solution. We then investigate combining individual queries into teams with the aim of capturing multiple SARs that may exist in a data set, for example, as is commonly seen in high-throughput screening data sets. Team formation is carried out iteratively as a postprocessing step following the evolution of the individual queries. The inclusion of uniqueness as a third objective within the MOEA provides an effective way of ensuring the queries are complementary in the active compounds they describe. Substantial improvements in both recall and precision are seen for some data sets. Furthermore, the resulting queries provide more detailed structure-activity information than is present in a single query.


A transition metal-free tandem process to pyridazinopyrido[3,2-f][1,4]thiazepine-diones via Smiles rearrangement.
A transition metal-free methodology for the synthesis of pyridazinopyrido[3,2-f][1,4]thiazepine-diones was studied. The construction of this tricyclic system went through a one-pot coupling/Smiles rearrangement/cyclization process. The high yields of pure products were obtained through simple recrystallization.


Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer's Disease.
We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aβ in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer's disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aβ-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer's disease.


Therapeutic strategies to protect the immature newborn myocardium during resuscitation following asphyxia.
Perinatal asphyxia contributes to over one million newborn deaths worldwide annually, and may progress to multiorgan failure. Cardiac dysfunction, of varying severity, is seen in 50%-70% of asphyxiated newborns. Resuscitation is necessary to restore oxygenation to deprived tissues, including the heart. However, reoxygenation of asphyxiated newborns may lead to generation of reactive oxygen species (ROS) and further myocardial damage, termed reperfusion injury. The newborn heart is especially vulnerable to oxidative stress and reperfusion injury due to immature antioxidant defense mechanisms and increased vulnerability to apoptosis. Currently, newborn myocardial protective strategies are aimed at reducing the generation of ROS through controlled reoxygenation, boosting antioxidant defenses, and attenuating cellular injury via mitochondrial stabilization.


Involvement of a calcium-phospholipid-dependent protein kinase in the maturation of Xenopus laevis oocytes.
It has been described that phosphorylation, and dephosphorylation, of specific proteins is associated with key events of the cell cycle and is likely to be due to activation of kinase(s). From our results, the presence of calcium-phospholipid-dependent protein kinase (PKC) was clearly demonstrated in both the cytosolic and particulate fractions of immature Xenopus laevis oocytes and in the cytosolic fraction of mature oocytes. However, it was less active in metaphase II- than in prophase I-arrested oocytes. The enzyme was partially purified by DEAE-cellulose and phenyl-Sepharose chromatography. It was activated in vitro by the tumor-promoting phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA) as already described for PKC from other tissues. On the other hand, a calcium-phospholipid-independent histone kinase activity 4-fold higher in metaphase II- than in prophase I-arrested oocytes was detected. The possible role of PKC and phospholipid-independent histone kinase in the maturation process is discussed.


Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.
Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.


Acute effects of alcohol on anterior pituitary secretion of the tropic hormones.
The plasma or serum concentrations of GH, TSH, LH, PRL, testosterone, cortisol, T4, and T3, and the values of the T3 uptake test were monitored in 12 healthy male volunteers for a period of 20 h after administration of one large dose of ethanol (1.5 g/kg BW). The effects of TRH and LRH on the secretion of TSH, PRL, and LH were studied in these subjects once during the period of acute alcohol intoxication (4 h after the start of drinking) and once during the hangover period (14 h after the start of drinking). Each subject served as his own control by drinking water only during another experimental session. Alcohol had no significant effect on basal concentrations of GH, TSH, LH, T4, T3, or testosterone. The concentration of cortisol in plasma was elevated during the whole 20-h period after ingestion of alcohol, as compared with the control values. Alcohol also did not significantly alter the effects of TRH and LRH on plasma TSH and LH levels at 4 and 14 h. During the hangover period, the PRL response to TRH was totally blocked, but during alcohol intoxication, there was a slight increase in the PRL response to TRH. The lack of response of PRL to TRH during the hangover suggests that withdrawal symptoms are associated with increased dopaminergic activity in the hypothalamus.


Development of a pressurized liquid extraction and clean-up procedure for the determination of alpha-endosulfan, beta-endosulfan and endosulfan sulfate in aged contaminated Ethiopian soils.
Pressurized liquid extraction (PLE) was investigated for the extraction of two endosulfan isomers and their metabolite from two real contaminated soil samples. PLE for 3x10min at 100 degrees C was proven to be more exhaustive than Soxhlet extraction (SOX) in one soil sample. On the other soil sample investigated the method was found to be equally exhaustive as SOX. The use of hazardous organic solvents such as n-hexane, toluene, and diethyl ether has been avoided in PLE and clean-up. Instead less toxic solvents have been used both at the extraction step (acetone/n-heptane) and clean-up step (ethyl acetate/n-heptane). A column Florisil clean-up procedure that consumes relatively low solvent volumes has been optimized and applied to purify soil extracts. The developed analytical procedure was validated by applying it to a certified reference soil material (CRM811-050). A recovery of 103% total endosulfan residue was obtained versus certified values.


What do patients want and do we want to know? A review of patients' requests of psychiatric services.
A systematic review was conducted of the literature concerning patients' requests of psychiatric care in order to identify the types of requests patients make, psychiatrists' perceptions of their patients' requests, and the relationship between requests and the outcome of care. A total of 28 published original articles which fulfilled specific inclusion criteria were reviewed. The studies showed that there are certain core requests that patients make irrespective of the type of service attended. Patients mainly request psychological approaches, and the most common requests are for 'clarification', 'psychological expertise' and 'psychodynamic insight'. There is evidence that patients normally feel inhibited about making requests, and that psychiatrists often fail to identify what their patients want. The majority of patients attending psychiatric services have requests which they will express when encouraged to do so, but little is known about the relationship between patients' requests and the outcome of care. Recommendations are made for future research.


Hypothermic renal protection using cold histidine-tryptophan-ketoglutarate solution perfusion in suprarenal aortic surgery.
We examined data of 21 patients who were treated with selective perfusion of both renal arteries with 500 mL of 8 degrees C histidine-tryptophan-ketoglutarate (HTK) solution each for renal protection during aortic surgery. Only the data from aortic surgeries with unavoidable suprarenal aortic cross-clamping for juxtarenal or suprarenal abdominal aortic aneurysms (AAAs) or high Leriche syndrome accompanied with stenosis of renal arteries are presented. Five patients underwent immediate surgery because of perforation of an AAA; the other 16 patients went through elective surgeries. In three cases (14%) stenosis of the renal arteries was diagnosed; nevertheless, implantation of an aortorenal bypass was necessary in seven patients. In total, 14 aortorenal bypasses were implanted (five venous grafts and nine prosthesis grafts). Four (19%) patients needed catecholaminergic support to establish stable circulatory conditions; in two (9%) of these cases additional ischemia of the colon was observed and sigmoidectomy was performed. All of these four patients underwent immediate surgery, and one died after surgery because of severe sepsis. In four cases postsurgical renal insufficiency was observed. Three of these patients were admitted for emergency surgery because of their hemodynamic situation due to perforation of the AAA. None of the patients needed chronic dialysis after surgery. Whereas in all patients who underwent elective surgery the renal function remained stable as judged by postoperative serum creatinine values, in five out of seven patients with aortorenal bypass surgery the renal function improved. Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients undergoing elective surgery with suprarenal cross-clamping of the aorta.


Parity As a Protective Biomarker Against Silent Brain Infarction in Community-Dwelling Older Adults: The Sefuri Study.
Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial. The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders. We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause. The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886). Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI.


Establishing the Turkish version of the SIGAM mobility scale, and determining its validity and reliability in lower extremity amputees.
The aim of this study is to adapt the Special Interest Group in Amputee Medicine (SIGAM) mobility scale to Turkish, and to test its validity and reliability in lower extremity amputees. Adaptation of the scale into Turkish was performed by following the steps in American Association of Orthopedic Surgeons (AAOS) guideline. Turkish version of the scale was tested twice on 109 patients who had lower extremity amputations, at hours 0 and 72. The reliability of the Turkish version was tested for internal consistency and test-retest reliability. Structural validity was tested using the "scale validity" method. For this purpose, the scores of the Short Form-36 (SF-36), Functional Ambulation Scale (FAS), Get Up and Go Test, and Satisfaction with the Prosthesis Questionnaire (SATPRO) were calculated, and analyzed using Spearman's correlation test. Cronbach's alpha coefficient was 0.67 for the Turkish version of the SIGAM mobility scale. Cohen's kappa coefficients were between 0.224 and 0.999. Repeatability according to the results of the SIGAM mobility scale (grades A-F) was 0.822. We found significant and strong positive correlations of the SIGAM mobility scale results with the FAS, Get Up and Go Test, SATPRO, and all of the SF-36 subscales. In our study, the Turkish version of the SIGAM mobility scale was found as a reliable, valid, and easy to use scale in everyday practice for measuring mobility in lower extremity amputees. Implications for Rehabilitation Amputation is the surgical removal of a severely injured and nonfunctional extremity, at a level of one or more bones proximal to the body. Loss of a lower extremity is one of the most important conditions that cause functional disability. The Special Interest Group in Amputee Medicine (SIGAM) mobility scale contains 21 questions that evaluate the mobility of lower extremity amputees. Lack of a specific Turkish scale that evaluates rehabilitation results and mobility of lower extremity amputees, and determines their needs, directed us to perform a study on this topic when we took the number of amputations performed in our country into consideration. SIGAM mobility scale is directed at rehabilitation specialists who are working in amputee medicine. Turkish version of this scale was found both reliable and valid in our study and hence it can be used in clinical practice and studies.


Structure and intracellular localization of mouse ADP-ribosylation factors type 1 to type 6 (ARF1-ARF6).
ADP-ribosylation factors (ARFs) are a family of small GTP-binding proteins that are proposed to be involved in the formation of coated transport vesicles. Although six ARF sequences have been reported in mammals to date, it has been unclear how many ARF members are present in a single organism. In this study, we provide the first direct evidence by cDNA cloning for the presence of all six ARF members in mouse. These proteins are highly conserved across mammalian species and Northern blot analysis revealed that mRNAs for all the members were expressed ubiquitously. Transfection of cells with epitope-tagged ARFs revealed that ARFs 1-3 displayed a perinuclear Golgi localization, while ARFs 4-6 appeared to be widely dispersed throughout the cytoplasm. These results suggest that although all the ARF proteins play fundamental and critical roles in cellular function, they are involved in different vesicular transport processes.


Haemopoietic receptors and helical cytokines.
A bewitching interplay of proteins, variously clothed as chemical messengers and cellular receptors, control the pace of growth and the course of progressive differentiation in blood cell types. The messengers are lymphokines, interleukins, colony-stimulating factors, growth hormones and interferons: generically, the cytokines. The second components of the regulatory pairs are membrane-spanning receptor proteins: these molecules transduce the specific binding of cognate cytokines into a mitogenic cellular response. In this article, Fernando Bazan discusses a provocative structural model for cytokine-receptor interactions which, if correct, will alter perceptions of the evolutionary design of the haemopoietic system.


Diagnosis of upper gastro-intestinal lesions by endoscopy, cytology and biopsy.
A prospective consecutive series of 210 upper gastrointestinal endoscopic procedures, at which material for both cytological and histopathological examination was obtained, was conducted at Baragwanath Hospital. The purpose of the study was to determine the respective and combined diagnostic value of endoscopic visualization, cytological brushings and histological sections in benign and malignant lesions of the oesophagus and stomach; and in particular to assess the contribution, if any, of exfoliative cytology to the diagnostic regimen. Endoscopic visualization alone was inconclusive or incorrect in 13% of procedures, cytology alone in 9%, and biopsy alone in 12% (the latter 2 figures corrected for adequacy of material submitted). When assessed together, the diagnostic accuracy achieved by all 3 techniques was 99%. The major contribution of cytology was the correct positive diagnosis in 20% of procedures, performed on patients with malignant lesions, whose initial biopsy specimen was inadequate or normal. It is concluded that for maximal diagnostic accuracy of upper gastro-intestinal lesions, a combined approach, utilizing endoscopic examination, lesion-directed brushings and biopsy specimens, is required.


Activated and interferon-gamma producing thyroid-derived T cells are detected in Graves' disease, thyroid autonomy as well as in non-toxic multinodular goiter.
The relative numbers of activated and interferon gamma (IFN-gamma)-producing peripheral blood lymphocytes (PBL) and thyroid-derived lymphocytes (TL) were determined using double surface and intracellular labeling techniques in flow cytometry. Cells were analyzed from 10 patients with Graves' disease (GD), eight patients with thyroid autonomy (TA) and five patients with non-toxic multinodular goiter (NTG). A maximum of 1% IFN-gamma+ cells were detected both in unstimulated PBL and TL. Stimulation caused a two- to threefold higher number of IFN-gamma+ cells in TL (GD, 48 +/- 12%; TA, 48 +/- 11%; NTG, 50 +/- 15%) as compared to PBL (GD, 15 +/- 7%; TA, 16 +/- 8%, NTG, 18 +/- 10%) of the same patients. Nearly all IFN-gamma+ TL in GD were CD3+ T cells, whereas 10-20% of IFN-gamma+ TL in TA and NTG were NK cells. In PBL 80% and in TL almost 100% of IFN-gamma+ cells were antigen-primed CD45RO+ cells. Only 25-35% of IFN-gamma+ thyroid-derived T cells expressed the CD4 antigen. About 42 +/- 10% thyroid-derived T cells in GD, 33 +/- 11% in TA and 34 +/- 13% in NTG expressed the HLA-DR molecule but not the interleukin 2 (CD25) or the transferrin receptor (CD71). Forty per cent of these HLA-DR+ T cells showed an intracellular staining for IFN-gamma and half of them co-expressed the activation antigen CD69. Immunofluorescence double labeling on thyroid cryostat sections demonstrated that HLA-DR+ T cells were also present in situ. The presence of activation antigens on thyroid-derived T cells not only in patients with GD but also in TA and NTG suggests failsafe mechanisms such as anergy, suppression or cytokine regulation in so-called non-immunogenic goiter.


Bone implants--a challenge to materials science.
The review paper discusses the conditions for obtaining in vivo a composite from a synthetic, inorganic material and collagen fibres. Bone itself is a composite containing collagen fibres and hydroxoapatite crystals. The crystal size is, however, far smaller than can be made using conventional methods of ceramics technology. The paper discusses therefore the possibilities to synthesize the apatite in a gel. The requirements of initial load bearing can be met by forming the gel on the surface of glass particle, sintered to a porous body. In the pores calcium ions react with the gel to form (= SiO)Ca+ complexes. When the phosphate concentration in the pore is high enough to exceed the solubility product of apatite, the calcium-gel complexes release the calcium and highly dispersed apatite crystallites are precipitated in the gel. These give the gel the osteoconductive properties observed for bioactive glasses. Glass compositions, which give a gel surface enough hydrated to form calcium complexes, are discussed.


Single-crystal 55Mn NMR spectra of two Mn12 single-molecule magnets.
The initial application is reported of single-crystal 55Mn NMR spectroscopy, and associated orientation dependence studies, to single-molecule magnets (SMMs). The studies were performed on two members of the Mn12 family of SMMs, [Mn12O12(O2CMe)16(H2O)4].2MeCO2H.4H2O (Mn12-Ac) and [Mn12O12(O2CCH2Br)16(H2O)4].4CH)Cl) (Mn12-BrAc). Single-crystal spectra give a dramatic improvement in the spectral resolution over oriented powder spectra, allowing the clear observation of quadrupolar splittings, the determination of quadrupole coupling parameters (e2qQ), and an assessment of the symmetry-lowering perturbation of the core of Mn12-Ac by hydrogen-bonding interactions with lattice solvate molecules of crystallization. The results emphasize the utility of single-crystal NMR studies to probe the cores of these magnetic molecules.


Identification - obstacle to individuation, or: on how to become 'me'.
This paper will explore the use of identification with aspects of a lost object as a defensive strategy to cope with traumatic loss, and will show how in the depth of the analytic work this identification can be accessed and made conscious. Descriptions of work with a three-year-old boy illustrate how the sudden loss of his mother's breasts had made weaning un-accessible to him, and how, in the absence of a good experience of separation, the process of mourning had not been able to take place. Instead, identification with aspects of the lost breast was used as a defence against pain, and this state of affairs was proving a hindrance to individuation. In the discussion of the case material, the use of identification as a defence will be highlighted, and a differentiation made between abandonment and separation as this illuminates the link between mourning and individuation.


Monitoring conformational dynamics with solid-state R 1rho experiments.
A new application of solid-state rotating frame (R(1rho)) relaxation experiments to observe conformational dynamics is presented. Studies on a model compound, dimethyl sulfone (DMS), show that R(1rho) relaxation due to reorientation of a chemical shift anisotropy (CSA) tensor undergoing chemical exchange can be used to monitor slow-to-intermediate timescale conformational exchange processes. Control experiments used d ( 6 ) -DMS and alanine to confirm that the technique is monitoring reorientation of the CSA tensor rather than dipolar interactions or methyl group rotation. The application of this method to proteins could represent a new site-specific probe of conformational dynamics.


Proteolytic processing of the beta-subunit of the lysosomal enzyme, beta-hexosaminidase, in normal human fibroblasts.
We have characterized the proteolytic processing of the beta-subunit of beta-hexosaminidase by identifying the amino termini of the various forms synthesized in cell-free translation and in cultured human fibroblasts. The procedures used had been developed for similar studies of the alpha-subunit (Little, L. E., Lau, M. M. H., Quon, D. V. K., Fowler, A. V., and Neufeld, E. F. (1988) J. Biol. Chem. 263, 4288-4292). Radioactive amino acids were incorporated biosynthetically into the different forms of the beta-subunit, which were isolated by immunoprecipitation, gel electrophoresis, and electroelution, and analyzed by automated Edman degradation. Translation by reticulocyte lysate in the presence of canine pancreas microsomes gave a product with alanine 43 at the amino terminus. The lysate could initiate translation at methionine 1 or methionine 13, depending on the SP6 mRNA provided. The product of signal peptidase action, the precursor form of the beta-subunit with amino-terminal alanine 43, was found in NH4+-induced secretions of cultured fibroblasts; intracellularly, this form was trimmed of two additional amino acids. The mature form was found to consist of three polypeptides joined by disulfide bonds; the amino termini were found to be valine 48, threonine 122, and lysine 315. Thus, in contrast to the alpha-subunit, the mature form of the beta-subunit of beta-hexosaminidase is derived from the precursor by internal proteolytic nicking rather than by removal of a large amino-terminal peptide segment.


Examining the relationships among item recognition, source recognition, and recall from an individual differences perspective.
The authors of the current study examined the relationships among item-recognition, source-recognition, free recall, and other memory and cognitive ability tasks via an individual differences analysis. Two independent sources of variance contributed to item-recognition and source-recognition performance, and these two constructs related differentially to other memory and cognitive ability constructs. The results are in accordance with a dual-process theory of memory retrieval in which a familiarity process can support judgments of previous occurrence and a more strategic recollection process is needed for controlled search of long-term memory. Furthermore, the authors offer additional evidence in favor of a dual-process model by showing validity for these two unique sources of variance.


The diagnostic threshold of HbA1c and impact of its use on diabetes prevalence-a population-based survey of 6898 Han participants from southern China.
The objective of this study is to determine the diagnostic threshold of HbA1c for diabetes and the impact of using it on diabetes prevalence. A population-based stratified study was conducted in 2010 among community-dwelling adults aged ≥35years in southern China. Participants without previously-diagnosed diabetes (PDD) took oral glucose tolerance test (OGTT) and HbA1c assay. HbA1c diagnostic threshold was determined by receiver operating characteristic curve. A total of 6989 participants with mean age of 52years were recruited. The area under curve of HbA1c was 0.903 (95% CI: 0.883-0.922), with optimal cut-off value at 6.25% (sensitivity 75.6% and specificity 91.9%). There were 449 (6.42%) patients with PDD and 422 (6.04%), 815 (11.66%) and 918 (13.13%) new cases diagnosed by OGTT, HbA1c ≥6.25% or either, respectively. When either HbA1c or OGTT was used, newly-diagnosed diabetes prevalence increased by 117.4%. Diabetes is prevalent in southern China. Near half of the patients go undetected with current diagnostic criteria. HbA1c ≥6.25% may be the diagnostic threshold value but needs further verification. The introduction of HbA1c threshold into diabetes diagnosis in China will cause a substantial increase in diabetes prevalence and great challenge on the public healthcare system.


Cbl promotes clustering of endocytic adaptor proteins.
The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.


TCR α+ β+ /CD19+ cell-depleted hematopoietic stem cell transplantation for pediatric patients.
TCR α+ β+ /CD19+ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α+ β+ /CD19+ cell-depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 108 /kg TNC, 12.1 × 106 /kg CD34+ cells, and 0.4 × 105 /kg TCR α+ β+ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8-22) and platelet engraftment 24 days (range 12-69). TRM at 1 year was 15%. Rate of grade II-IV aGVHD at 1 year was 20% with no grade III-IV aGVHD seen. CMV reactivation occurred in 81% of CMV-positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 106 /L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α+ β+ /CD19+ cell-depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.


A stable sulfone based electrolyte for high performance rechargeable Li-O2 batteries.
A tetramethylene sulfone based electrolyte was used in rechargeable Li-O(2) batteries for the first time. Without a catalyst, superior battery performances were successfully obtained, and desired lithium peroxide (Li(2)O(2)) dominates the discharge product.


Extra-individual sources of social support as described by adults with mild intellectual disabilities.
The extra-individual social support responses provided by adults with intellectual disabilities on a social support survey were examined. Felton and Berry (1992) argued that extra-individual social support, support from larger than individual entities, is a valid source of social support for older adults. We hypothesized that extra-individual support would also be relevant to adults with intellectual disabilities. Results showed that 43% of participants with intellectual disabilities listed extra-individual support sources in their social networks or as providers of one of several support functions. The most popular forms of extra-individual support were those from "staff" and "work." Findings are discussed in terms of implications for social support measurement for persons with intellectual disabilities.


Structure and characterization of AAT-1 isoforms.
A novel protein, AAT-1, was identified as a AMY-1-binding protein and three splicing variants of AAT-1, AAT-1alpha, -beta and -gamma were identified. The function of AAT-1 is thought to be related to spermatogenesis. In this study, we further identified other splicing isoforms of AAT-1, AAT-1L, AAT-1M and AAT-1S, consisting of 767, 603 and 252 amino acids, respectively. These isoforms were found to use a promoter different from that used by AAT-1alpha, -beta and -gamma in the aat-1 gene, which contains 20 exons. Only 60 amino acids in the C-terminal portion of AAT-1 derived from exons 15-17 are common among AAT-1L, AAT-1M, AAT-1S and AAT-1alpha. While AAT-1alpha is specifically expressed in the testis, AAT-1L, AAT-1M, AAT-1S were found to be differentially expressed in human tissues. All of the isoforms of AAT-1 were found to bind to and colocalized with AMY-1 in human cells. While AAT-1L and AAT-1M were found to be localized diffusely in the cytoplasm, AAT-1S, like AAT-1alpha, was found to be localized in the mitochondria-like structure, suggesting different roles of AAT-1 isoforms in cells.


Prolonged intermittent high intensity exercise impairs neuromuscular performance of the knee flexors.
This study investigated the effect of prolonged intermittent high intensity exercise upon the isokinetic leg strength and electromechanical delay of the knee flexors. Seven male collegiate soccer players were exposed to: (i) a prolonged intermittent high intensity exercise task (PIHIET) which required subjects to complete a single-leg pedalling task, with the preferred limb, (75 rpm for all constant-load portions of the task) consisting of 48 x 1.8 minute cycles of exercise, and (ii) a control task consisting of no exercise. Pre-, mid- and post-PIHIET gravity corrected indices of knee flexion angle-specific torque (0.44 rad knee flexion (AST); 0 rad=full knee extension; [1.05 rad x s(-1)]) were made for both intervention and control limbs. Electromechanical delay (EMD) of the m. biceps femoris during supine knee flexion movements was evaluated in the preferred leg on both intervention and control days. Repeated measures ANOVAs revealed significant condition (intervention; control) by time (pre; mid; post) interactions for both knee flexor AST (F[2,12]=4.8; p < 0.03) and EMD (F[2,12]=4.1; p < 0.05). AST was observed to decrease by 16% and EMD increase by 30% pre to post intervention. These observations suggest an impairment of neuromuscular control and the ability to maintain force generation in the knee flexors, near the extremes of the range of motion during prolonged intermittent high-intensity exercise activities. Changes of this magnitude may pose a threat to the integrity of the knee joint.


A field test of inverse modeling of seed dispersal.
Seed dispersal distance-a key process in plant population dynamics-remains poorly understood because of the difficulty of finding a source plant so well isolated from conspecifics that seeds or seedlings can be unambiguously attributed to it. Inverse modeling (IM) of seed dispersal, a simple statistical technique for parameterizing dispersal kernels, has been widely used since 1992; surprisingly, however, this approach has never been verified in the field. We released from 20 nearby trees the winged seeds of a liana species, Entada polystachya, near the coast in a tropical, dry forest in Jalisco, Mexico. With a two-parameter log-normal function, we found that IM predicted both the shape and scale parameters well as long as we used the entire data set. When, however, we subsampled (thus simulating the use of transects for seedlings or an array of seed traps), the estimates of the scale and shape parameters were often more than double the real values. The problem was due to the marked anisotropy (directional bias; in this case, in the direction of the diurnal sea breeze) of the individual dispersal curves. When we randomized the direction of dispersal of individual seeds from the trees (keeping dispersal distances unchanged), predictions of parameter values were excellent. Inverse modeling must include directional parameters when dealing with areas where strong anisotropy is to be expected, e.g., for wind dispersal of seeds near coasts or pollination by any vector where a plant species is limited to a strongly linear habitat such as river banks.


Responsiveness and minimal clinically important change in overactive bladder symptom score.
To assess the responsiveness and minimal clinically important change (MCIC) in the Overactive Bladder Symptom Score (OABSS), a single score used to quantify overactive bladder symptoms. The data were derived from a clinical trial of propiverine in patients with overactive bladder. The analysis included participants who completed the OABSS, a bladder diary, and patient-reported outcome measures (urgency and incontinence impact) at baseline and 12 weeks. Responsiveness was assessed with effect sizes, correlations between the OABSS items and bladder diary variables, and comparisons between the score changes and symptom improvement. The MCIC was comprehensively estimated from the discriminating thresholds for minimal symptom improvement, and the receiver operating characteristics curve analyses were used to derive cutoff scores for symptom improvement. A total of 282 participants were included in the present analysis. The effect sizes for the OABSS ranged from -0.369 to -1.485, and correlations between the changes in the OABSS items and the corresponding bladder diary variables were moderate to large. A linear tendency was found between the changes in the OABSS and symptom improvement. The mean change for urgency and incontinence impact was -2.59 and -2.49 for "no change" and -3.67 and -3.78 for "minor improvement," respectively. The optimal cutoff score ranged from -4 to -3. Integrating the MCIC analyses, -3 was estimated as the minimal threshold for a meaningful change. With good responsiveness, the OABSS is a useful tool for assessing the treatment of OAB symptoms. Furthermore, the results of our study suggest that the MCIC of the OABSS is -3.


Georeferencing of deaths from sepsis in the city of São Paulo.
The aim of the present study was to obtain information about deaths due to sepsis in São Paulo from 2004 to 2009 and their relationship with geographical distribution. Causes of death, both main and secondary, were defined according to the codes of the International Classification of Disease version 10 (ICD-10) contained in the database. Sepsis, septic shock, multiple organ failure, pneumonia, urinary tract infection, peritonitis and other intraabdominal infections, skin and soft tissue infections (including surgical wound infection) and meningitis were considered as immediate cause of death or as the condition leading to the immediate cause of death related or associated to sepsis. In the analyzed period, there was a 15.3% increase in the absolute number of deaths from sepsis in São Paulo. The mean number of deaths during this period was 28,472±1566. Most deaths due to sepsis and sepsis-related diseases over the studied period occurred in a hospital or health care facility, showing that most of the patients received medical care during the event that led to death. We observed a significant concentration of deaths in the most populous regions, tending more toward the center of the city. Georeferencing data from death certificates or other sources can be a powerful tool to uncover regional epidemiological differences between populations. Our study revealed an even distribution of sepsis all over the inhabited areas of São Paulo.


Complications associated with immunosuppressive therapy and their management.
Besides general complications of immunosuppression such as increased susceptibility to opportunistic infections or malignancy, individual immunosuppressive agents are associated with specific side effects. Nephrotoxicity is the major side effect of cyclosporine (CsA). Various attempts have been made to minimize this toxicity, such as monitoring drug blood levels, modifying the protocol, and coadministering other agents. Other side effects caused by CsA are hepatotoxicity, hyperkalemia, hypertension, tremor, gum overgrowth, and hirsutism. Azathioprine (AZA) causes dose-related bone marrow suppression, commonly leading to leukopenia. Careful monitoring of complete blood cell count and dosage adjustment according to white blood cell count are usually adequate to prevent serious leukopenia. The side effects of corticosteroids are numerous and include slow wound healing and de novo insulin-dependent diabetes mellitus. Many complications are dose related, and with low dosage or discontinuation of steroids, their frequency rapidly decreases. Antilymphoblast and antithymocyte globulins (P-ALG) are foreign antibodies and may cause allergic-type reactions such as fever, chill, and hypotension. The initial side effect of monoclonal antibody (muromonab-CD3, OKT3) is similar to that of P-ALG. It includes high fever, shaking chills, headache, rigors, and hypotension. To prevent it, acetaminophen, an antihistamine, and a steroid usually are administered before injection. Because this agent is also associated with high frequency of pulmonary edema, it should not be given to any patient who has more than 3% body weight gain during the week prior to therapy. In rare case, it causes aseptic meningitis or encephalopathy, which is manifested by fever, severe headache, and seizure.


A genetic study of 2,000-year-old human remains from Japan using mitochondrial DNA sequences.
We present nucleotide sequence data for mitochondrial DNA extracted from ancient human skeletons of the Yayoi era (ca. 2,000 BP) excavated from the Takuta-Nishibun site in northern Kyushu of Japan. Nucleotide sequence diversity showed that the Yayoi people of the Takuta-Nishibun site were not a genetically homegeneous population. This site shows a diversity in the burial style. Phylogenetic analysis indicated a statistically significant correlation between burial style and the genetic background of the Takuta-Nishibun individuals, and revealed no discrete clusterig patterns for the Yayoi individuals, for early modern Ainu, or for the Jomon people.


Examination of Collagen Structure and State by the Second Harmonic Generation Microscopy.
Collagen is the major component of the extracellular matrix in mammals and its characteristics provide important information about the state of connective tissue. There are only few methods of label-free visualization of collagen fibers; the most frequently used is the second harmonic generation (SHG) microscopy. SHG microscopy is a non-invasive technique for the assessment of the abundance and structure of fibrillar collagen with a high resolution and specificity. At constant measurement parameters (magnification, excitation power, resolution, digital gain of registration matrix), quantitative analysis of SHG images provides a reliable characterization of collagen state. Current approaches to the SHG signal quantification are numerous and typically should be adapted to a specific task. In this review, we systematize the variety of these approaches and present the examples of biomedical application of the SHG signal quantitative analysis, as well of combined application of SHG and autofluorescence imaging.


A Comparison of Dressing Techniques for Presurgical Closure of Myelomeningocele in the Neonate.
Myelomeningoceles are routinely closed surgically within 24 to 48 hours after birth; the defect and exposed placode must be protected from further damage from excoriation and contamination until surgery. Two methods to keep the defect moist and clean are used at our large Midwestern children's hospital: the occlusive and the drip. There was no agreement between the neonatal and neurosurgical teams as to which technique was superior, hence the need for a formal evaluation. A prospective, randomized trial was conducted to compare the ease of nursing care, cost of supplies, neonatal temperature, and moisture of the placode at the time of closure in neonates with a myelomeningocele. Nurses categorized the occlusive group as easy care (100%) compared with 60% for the drip group, although the difference was not statistically significant (P = .18). The mean temperatures of the 2 groups before surgery were identical (36.9°C) in both groups. The cost of the drip was 6 times higher than that of the occlusive technique. The placode was assessed as moist in all 13 cases (100%). The occlusive technique was easier to care for by all the nurses and was 6 times more cost effective. Both methods kept the placode moist and did not affect the temperature of the baby.


Critical thinking and accuracy of nurses' diagnoses. Part I: Risk of low accuracy diagnoses and new views of critical thinking.
Interpretations of patient data are complex and diverse, contributing to a risk of low accuracy nursing diagnoses. This risk is confirmed in research findings that accuracy of nurses' diagnoses varied widely from high to low. Highly accurate diagnoses are essential, however, to guide nursing interventions for the achievement of positive health outcomes. Development of critical thinking abilities is likely to improve accuracy of nurses' diagnoses. Newer views of critical thinking serve as a basis for critical thinking in nursing. Seven cognitive skills and ten habits of mind are identified as dimensions of critical thinking for use in the diagnostic process.


Predictive value of 16-slice multidetector spiral computed tomography to detect significant obstructive coronary artery disease in patients at high risk for coronary artery disease: patient-versus segment-based analysis.
In this study, we investigated the diagnostic value and limitations of multidetector computed tomography (MDCT)-based noninvasive detection of significant obstructive coronary artery disease (CAD) in a consecutive high-risk patient population with inclusion of all coronary segments. In a prospective, blinded, standard cross-sectional technology assessment, a cohort of 33 consecutive patients with a positive stress test result underwent 16-slice MDCT and selective coronary angiography for the detection of significant obstructive CAD. We assessed the diagnostic accuracy of MDCT in a segment-based and a patient-based model and determined the impact of stenosis location and the presence of calcification on diagnostic accuracy in both models. Analysis of all 530 coronary segments demonstrated moderate sensitivity (63%) and excellent specificity (96%) with a moderate positive predictive value of 64% and an excellent negative predictive value (NPV) of 96% for the detection of significant coronary stenoses. Assessment restricted to either proximal coronary segments or segments with excellent image quality (83% of all segments) led to an increase in sensitivity (70% and 82%, respectively), and high specificities were maintained (94% and 93%, respectively). In a patient-based model, the NPV of MDCT for significant CAD was limited to 75%. Coronary calcification was the major cause of false-positive findings (94%). For all coronary segments included, 16-slice MDCT has moderate diagnostic value for the detection of significant obstructive coronary artery stenosis in a population with a high prevalence of CAD. The moderate NPV of patient-based detection of CAD suggests a limited impact on clinical decision-making in high-risk populations.


Variations in cadmium accumulation and distribution among different oilseed rape cultivars in Chengdu Plain in China.
Cadmium (Cd) is a widespread toxic heavy metal trace pollutant worldwide. The ability of Cd absorption and accumulation highly varies among different species and varieties. In order to screen oilseed rape cultivars which are appropriate for cultivation and application in Cd-contaminated soils, we conducted the field trial of 32 oilseed rape varieties in Shifang County of Chengdu Plain. The various biomass, Cd accumulation, and distribution patterns were investigated via determining the Cd concentration in different plant tissues. Moreover, the food safety risks of rapeseeds were finally assessed. The results indicated diverse responses to Cd stress appeared in various tested varieties, including plant biomass, seed yield, Cd concentration, and proportion in different tissues. And most Cd were concentrated in non-edible parts. Through cluster analysis, we found that Nanchongjie, Pengzhoubai, and J-25 belong to high-biomass and high-Cd-accumulated groups in experimental cultivars, which indicated that they could possess more biomass and gather higher Cd content in overground part, so they could be great materials for phytoremediation in Cd-polluted area. Besides, combined with the risk assessment of food safety in rapeseeds, cultivars 72A and 47 with the traits of high yield, low-Cd concentration, and low food safety risk can be considered as suitable materials to widely plant as cash crop. These results provide valuable reference for practical planting and application of oilseed rape in Cd-polluted areas.


Pediatric cancer in the United States. A preliminary report of a collaborative study of the Childrens Cancer Group and the Pediatric Oncology Group.
Cancer is the second leading cause of death in children younger than 15 years. Although 5-year survival rates have increased dramatically for many childhood tumors, more than 100,000 person-years of life are lost to childhood cancer each year. The exact proportion of pediatric patients with cancer who receive care at centers that use up-to-date therapeutic protocols (such as those affiliated with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG) is unknown. Based on residence at the time of diagnosis, observed numbers of pediatric cancer cases seen by member institutions of the CCG and the POG in 1989 and 1990 were compared with the expected number of cases. Expected values were calculated from incidence rates obtained from the Surveillance, Epidemiology and End Results Program and population counts obtained from the US Census Bureau. Results indicate that more than 90% of children younger than 15 years who have a diagnosis of malignant neoplasm are seen at an institution that is a member of either CCG or POG. The highest proportion seen occurs in the youngest (0-4 years) age group, and the proportion declines steadily with increasing age. There are specific regions within the United States where the observed number of cases was substantially less than the expected number, including areas of Texas, Idaho, and Virginia. Although the exact reasons for these potential deficits are unknown, additional study of these areas is recommended.


An agonist that is selective for adenylate cyclase-coupled muscarinic receptors.
Compound BM5 [N-methyl-N(1-methyl-4-pyrrolidino-2-butynyl) acetamide] has previously been described as an agonist at postsynaptic muscarinic receptors and as an antagonist at presynaptic receptors. In the current work, we studied the ability of this compound to selectively stimulate phosphoinositide (PI) turnover in Chinese hamster ovary cells transfected with m1 muscarinic receptors and in SK-N-SH neuroblastoma cells that express only m3 receptors. We also studied the ability of this compound to stimulate adenylate cyclase inhibition in m2 muscarinic receptors from heart tissue and in m4 receptors expressed in NG108-15 cells. BM5 stimulated the two muscarinic receptor subtypes coupled to adenylate cyclase inhibition. In NG108-15 cells, 100 microM BM5 inhibited prostaglandin E1-stimulated cAMP formation by 36 +/- 1.5%, whereas 100 microM of the full agonist oxotremorine-M inhibited cAMP formation by 64.1 +/- 1.9%. The half-maximal concentration for BM5 inhibition of cAMP formation was 0.4 +/- 0.1 microM. In heart membranes, BM5 inhibited isoproterenol-stimulated adenylate cyclase by 24 +/- 2%, whereas oxotremorine inhibited this activity by 34 +/- 3%. In contrast to its activity at these receptor subtypes, BM5 did not stimulate the m1 or m3 receptor subtypes, which couple to PI turnover. In these latter two subtypes, BM5 inhibited oxotremorine-M-stimulated PI turnover with IC50 values of 10-20 microM. Therefore, BM5 is a partial agonist at adenylate cyclase-coupled muscarinic receptor subtypes and is a pure antagonist at PI turnover-coupled muscarinic receptor subtypes. These studies also suggest that, at least in some parts of the brain, postsynaptic muscarinic receptors are coupled to adenylate cyclase, whereas presynaptic muscarinic receptors are coupled to PI turnover.


Infectious keratitis: correlation between corneal and contact lens cultures.
This article reports a study of the effectiveness of performing contact lens cultures to identify causative organisms of infectious keratitis in patients using extended-wear soft contact lenses (cosmetic or therapeutic). Patients' records from the Ocular Microbiology Laboratory of the Department of Ophthalmology, Paulista School of Medicine, from 1976 to 2000, and data of patients with contact lens-related keratitis in which the contact lens had been cultured were collected and reviewed. One hundred thirteen patients were included. Only soft contact lenses had been cultured and 29.2% of them were therapeutic contact lenses. An overall concordance of 84.0% was found between cultures obtained from corneal scrapings and contact lenses, with a higher rate in fungal keratitis (100%) compared to amebic (80.0%) and bacterial (74.5%) keratitis. In cases of concomitant bacterial growth in cultures of scrapings and contact lenses, the same organism was detected in 97.04%. Most cases of bacterial infection were caused by Pseudomonas spp. Among the discordant cases (16%), a microorganism was more likely to be isolated by contact lens culture (94.4%). Contact lens cultures may identify the causative organisms in most cases of contact lens-related keratitis. The clinical relevance of positive contact lens cultures in keratitis with negative corneal cultures needs further investigation.


Molecular model for a complete clathrin lattice from electron cryomicroscopy.
Clathrin-coated vesicles are important vehicles of membrane traffic in cells. We report the structure of a clathrin lattice at subnanometre resolution, obtained from electron cryomicroscopy of coats assembled in vitro. We trace most of the 1,675-residue clathrin heavy chain by fitting known crystal structures of two segments, and homology models of the rest, into the electron microscopy density map. We also define the position of the central helical segment of the light chain. A helical tripod, the carboxy-terminal parts of three heavy chains, projects inward from the vertex of each three-legged clathrin triskelion, linking that vertex to 'ankles' of triskelions centred two vertices away. Analysis of coats with distinct diameters shows an invariant pattern of contacts in the neighbourhood of each vertex, with more variable interactions along the extended parts of the triskelion 'legs'. These invariant local interactions appear to stabilize the lattice, allowing assembly and uncoating to be controlled by events at a few specific sites.


RF-powered BIONs for stimulation and sensing.
Virtually all bodily functions are controlled by electrical signals in nerves and muscles. Electrical stimulation can restore missing signals but this has been difficult to achieve practically because of limitations in the bioelectric interfaces. Wireless, injectable microdevices are versatile, robust and relatively inexpensive to implant in a variety of sites and applications. Several variants are now in clinical use or under development to perform stimulation and/or sensing functions and to operate autonomously or with continuous coordination and feedback control.


[The conservative treatment of early-stage benign prostatic hypertrophy].
After outlining the methods currently used in benign prostate hyperplasia (BPH) treatment, data defining some etiological aspects of the disease are briefly analyzed. Initial experience had with the treatment of early stage BPH using Permixon--a drug exerting effect on alpha-2 reductase--is described. The results in a series of twenty-seven patients presenting BPH are encouraging.


Dacron femoral-popliteal bypass grafts in good-risk claudicant patients.
To evaluate prosthetic femoral-popliteal (FP) grafts as bypass conduits in favorable patients with refractory calf claudication. University-affiliated urban teaching hospital. Cohort study of patency of 6-mm Dacron FP grafts used to treat patients with medically refractory calf claudication meeting the following criteria: nonsmoker; above-knee popliteal artery as an appropriate target vessel; > or =2-vessel tibial outflow; and postoperative anticoagulation and antiplatelet therapy. End points included primary and secondary FP graft patency, need for and outcome of subsequent intervention, limb amputation, and survival. From January 1998 through March 2001, 92 patients underwent 100 Dacron bypass grafts for medically refractory claudication. All underwent serial postoperative graft surveillance using duplex ultrasound. Using the Society for Vascular Surgery/International Society of Cardiovascular Surgery criteria life-table, primary patency was 84%, assisted primary patency was 88%, and secondary patency was 90% at 5 years. Two patients (2%) died during a mean follow-up period of 49 months (range 30 to 68). No limbs required amputation. Among 9 limbs in which Dacron FP bypass failed, 8 underwent subsequent successful autogenous bypass to the popliteal artery. In highly selected subjects with favorable features known to increase the likelihood of prosthetic graft patency, prosthetic FP grafts function well. Such patients undergo a simpler, more straightforward procedure than when autogenous FP bypass is performed. Subsequent success of autogenous FP repeat bypass suggests that previous prosthetic FP bypass does not threaten lower-extremity arterial outflow.


The effect of digitalis on the bladder in man.
The effects of intravenous digitalis on the bladder were investigated in 36 patients. Digitalis consistently decreased the bladder capacity and in some it increased the intravesical pressure. The significance of these findings and its clinical applications are discussed.