Transcriptional control of fetal liver hematopoiesis: dominant negative effect of the overexpression of the LIM domain mutants of LMO2.
The LIM-finger protein LMO2 forms a transcription factor complex with other hematopoietic regulator proteins, such as TAL1 (SCL), LDB1, GATA1, 2, and 3, in the promoters of several erythroid genes. To elucidate the functional role of two LIM domains in LMO2, we introduced deletion or mutation in each of the LIM domains and analyzed their phenotypic effects on the hematopoietic system when overexpressed in vivo or in vitro. Protein interactions of LIM-modified LMO2 constructs with TAL1, LDB1, and GATAs were examined in an immunoprecipitation assay. In vivo hematopoiesis in transgenic mice with wild-type and LIM-modified Lmo2 was studied morphologically and by measuring the progenitor cells in fetal liver. Their effects on the erythroid differentiation of the dimethylsulfoxide (DMSO)-induced murine erythroleukemia (MEL) cells were evaluated. Deletion of the LIM2 domain, but not of the LIM1 domain, abolished its binding of GATA proteins. Overexpression of wild-type LMO2 is known to have dominant negative inhibitory effects on erythropoietic development. Enforced expression of LMO2 constructs with mutant or absent LIM2 but with an intact LIM1 domain resulted in fetal death, small livers and hearts, and decreased hematopoiesis, as well as a hypoplastic thymus. DMSO-induced erythroid differentiation of the MEL cells was inhibited by the overexpressed LMO2 with mutant LIM2 but not by the LMO2 with modified LIM1. Overexpression of the LMO2 with modified LIM2 inhibited hematopoiesis probably by interfering with the formation of the physiological complex or by replacing the functional LMO2 with mutants with reduced affinity to GATA proteins. In this experiment, no evident effect of the LMO2 with modified LIM1 could be observed.


[Evaluation of lymphatic emboli in gastric cancer by D2-40/CKpan dual immunostain and its significance].
To investigate the evaluation of lymphatic emboli by D2-40/CKpan dual immunostain and its prognostic significance in advanced primary gastric adenocarcinoma. Tissue samples of 108 cases of advanced gastric adenocarcinoma with radical gastrectomy were collected from Chinese PLA General Hospital in 2001. Lymphatic emboli were evaluated by D2-40/CKpan dual immunostain on consecutive sections, and compared with routine HE staining. The correlation of lymphatic emboli with lymph node metastasis and overall survival was analyzed by Pearson Chi-squared test and univariate survival analysis, respectively. Lymphatic emboli were detected in 73/108 (67.6%) cases by D2-40/CKpan staining, compared to 57/108 (52.8%) by HE staining. There was significant difference (P=0.007). Lymphatic emboli on HE staining revealed false negative in 24/108 cases and false positive in 8/108 cases. A significant correlation was found between lymphatic emboli and lymph node metastasis on HE staining (P=0.024), while it was not found on D2-40/CKpan staining (P=0.422). The overall survival rate was significantly different between lymphatic emboli positive and negative cases on HE staining (P=0.043). The overall survival rate was lower in lymphatic emboli positive cases on HE staining. Lymphatic emboli evaluated on D2-40/CKpan staining had no prognostic value (P=0.402). D2-40/Ckpan dual immunostaining is more sensitive for lymphatic emboli in gastric adenocarcinoma but may not predict lymph node metastasis and survival, while HE staining may.


[Analysis of correlation between physical training and autonomic function by using multivariate analysis: establishing an indicator of health].
The purpose of this study is to assess the effects of physical training on autonomic nervous function. Twenty-two healthy subjects(12 males and 10 females) participated in this study. We inquired contents of the exercise for each subject. Continuous ECG was recorded during 320 seconds at supine resting. Respiratory rhythm was fixed at 0.25 Hz(15 time/min). On the basis of spectral analysis of heart rate variability, the autonomic nervous function was assessed by low frequency power(LF: 0.06-0.13 Hz) and high frequency power(HF: 0.16-0.50 Hz). The predominance of sympathetic nervous activity were indicated by the LF/HF and LF-HF. Relationship between physical training and autonomic function was analyzed by using multivariate analysis(partial correlation analysis). As the results, LF power and LF-HF negatively correlated with training time per day, energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). HF power positively correlated with energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). These results indicate not training time but energy expenditure alters the autonomic nervous function. This index may be useful for evaluating training effect on the promotion of health.


Cognitive processing speed deficits in multiple sclerosis: Dissociating sensorial and motor processing changes from cognitive processing speed.
The assessment of cognitive information processing speed (IPS) is complicated in MS, with altered performance on tests such as the Symbol Digit Modalities Test (SDMT) potentially representing changes not only within cognitive networks but in the initial sensorial transmission of information to cognitive networks, and/or efferent transmission of the motor response. We aimed to isolate and characterise cognitive IPS deficits in MS using ocular motor tasks; a prosaccade task (used to assess and control for sensorial and motor IPS) which was then used to adjust performance on the Simon task (cognitive IPS). All participants (22 MS patients with early disease, 22 healthy controls) completed the ocular motor tasks and the SDMT. The Simon task assessed cognitive IPS by manipulating the relationship between a stimulus location and its associated response direction. Two trial types were interleaved: (1) congruent, where stimulus location = response direction; or (2) incongruent, where stimulus location ≠ response direction. RESULTS MS patients did not perform differently to controls on the SDMT. For OM tasks, when sensorial and motor IPS was controlled, MS patients had significantly slower cognitive IPS (incongruent trials only) and poorer conflict resolution. SDMT performance did not correlate with slower cognitive IPS in MS patients, highlighting the limitation of using SDMT performance to interpret cognitive IPS changes in patients with MS. Cognitive IPS deficits in MS patients are dissociable from changes in other processing stages, manifesting as impaired conflict resolution between automatic and non-automatic processes. Importantly, these results raise concerns about the SDMT as an accurate measure of cognitive IPS in MS.


Two-phase anaerobic digestion of vegetable market waste fraction of municipal solid waste and development of improved technology for phase separation in two-phase reactor.
Biogas production from vegetable market waste (VMW) fraction of municipal solid waste (MSW) by two-phase anaerobic digestion system should be preferred over the single-stage reactors. This is because VMW undergoes rapid acidification leading to accumulation of volatile fatty acids and consequent low pH resulting in frequent failure of digesters. The weakest part in the two-phase anaerobic reactors was the techniques applied for solid-liquid phase separation of digestate in the first reactor where solubilization, hydrolysis and acidogenesis of solid organic waste occur. In this study, a two-phase reactor which consisted of a solid-phase reactor and a methane reactor was designed, built and operated with VMW fraction of Indian MSW. A robust type filter, which is unique in its implementation method, was developed and incorporated in the solid-phase reactor to separate the process liquid produced in the first reactor. Experiments were carried out to assess the long term performance of the two-phase reactor with respect to biogas production, volatile solids reduction, pH and number of occurrence of clogging in the filtering system or choking in the process liquid transfer line. The system performed well and was operated successfully without the occurrence of clogging or any other disruptions throughout. Biogas production of 0.86-0.889m3kg-1VS, at OLR of 1.11-1.585kgm-3d-1, were obtained from vegetable market waste, which were higher than the results reported for similar substrates digested in two-phase reactors. The VS reduction was 82-86%. The two-phase anaerobic digestion system was demonstrated to be stable and suitable for the treatment of VMW fraction of MSW for energy generation.


Gastroesophageal reflux in children.
Gastroesophageal reflux (GOR) is a major cause of morbidity and failure to thrive particularly in neurologically impaired children. Clinical manifestations of GOR in children range from regurgitation, food refusal, irritability, failure to thrive, hematemesis, wheezing and aspiration pneumonia, apnoea and apparent life threatening events in infants to clinically silent reflux. Although, no one test is always best to diagnose GOR, 24 hour esophageal pH monitoring remains the 'gold standard' for diagnosis. Barium radiography is useful for the diagnosis of associated anatomical abnormalities and endoscopy enables a histological diagnosis of esophagitis. Therapy for gastroesophageal reflux disease is now well established. Proper positioning of the baby and thickening of feeds is beneficial in uncomplicated GOR. Prokinetic agents like cisapride should be tried if dietary management and antacids are ineffective. Metoclopramide or domperidone may be tried in neurologically impaired children. H2-receptor antagonists are indicated in GOR complicated by esophagitis. Ranitidine is regarded to be more potent. Cimetidine has additional spectrum of adverse effects and sufficient information is not available on famotidine. Omeprazole has been shown to be effective in treating GOR-esophagitis resistant to H2 antagonist therapy even in high risk patients.


Electrodeposition of catalytic and magnetic gold nanoparticles on dendrimer-carbon nanotube layer-by-layer films.
Magnetic and catalytic gold nanoparticles were electrodeposited through potential pulse on dendrimer-carbon nanotube layer-by-layer (LbL) films. A plasmon absorption band at about 550 nm revealed the presence of nanoscale gold in the film. The location of the Au nanoparticles in the film was clearly observed by selecting the magnetic force microscopy mode. To our knowledge, this is the first report on the electrochemical synthesis of magnetic Au nanoparticles. In addition to the magnetic properties, the Au nanoparticles also exhibited high catalytic activity towards ethanol and glycerol oxidation in alkaline medium.


[Effect of sulfur salt-bromine-iodine thermal waters on albumin and IgA concentrations in nasal secretions].
In chronic rhinopharyngotubaric phlogoses, the key pathogenic element sustaining phlogosis is a persistent modification of the biological, rheological features of the nasal mucus. For centuries sulphurous thermal waters have proved effective in clinically curing such phlogoses. In order to evaluate the effect of such sulphurous-salty-bromic-iodic thermal waters a randomized, double blind study was undertaken on a sampling of 50 patients. The effect such waters have on secretory IgA (sIgA) and albumin in the nasal secretions was tested against a placebo made of distilled water. Using the method of radial immunodiffusion, the response in the IgAs (mg/l) and albumin (mg/dl) concentrations in the nasal secretions was measured for 25 patients treated with the thermal waters and 25 patients treated with distilled water. The average concentrations were statistically compared using the Student t-test for paired samples. A significant increase (p < 0.0001) was seen in the mean IgAs concentration in the patients treated with the thermal waters. On the other hand, there was a weak, not statistically significant increase in the same data mean for the group treated with distilled water. The average increase in the albumin concentration in the nasal secretions proved significant in both cases although the significance was much more marked in the group treated with the thermal waters (p = 0.001) vs. the placebo group (p = 0.039).


Stress or no stress: mineralocorticoid receptors in the forebrain regulate behavioral adaptation.
Corticosteroid effects on cognitive abilities during behavioral adaptation to stress are mediated by two types of receptors. While the glucocorticoid receptor (GR) is mainly involved in the consolidation of memory, the mineralocorticoid receptor (MR) mediates appraisal and initial responses to novelty. Recent findings in humans and mice suggest that under stress, the MR might be involved in the use of different learning strategies. Here, we used male mice lacking the MR in the forebrain (MR(CaMKCre)), which were subjected to 5-10 min acute restraint stress, followed 30 min later by training trials on the circular hole board. Mice had to locate an exit hole using extra- and intra-maze cues. We assessed performance and the use of spatial and stimulus-response strategies. Non-stressed MR(CaMKCre) mice showed delayed learning as compared to control littermates. Prior stress impaired performance in controls, but did not further deteriorate learning in MR(CaMKCre) mice. When stressed, 20-30% of both MR(CaMKCre) and control mice switched from a spatial to a stimulus-response strategy, which rescued performance in MR(CaMKCre) mice. Furthermore, MR(CaMKCre) mice showed increased GR mRNA expression in all CA areas of the hippocampus and an altered basal and stress-induced corticosterone secretion, which supports their role in the modulation of neuroendocrine activity. In conclusion, our data provide evidence for the critical role of MR in the fast formation of spatial memory. In the absence of forebrain MR spatial learning performance was under basal circumstances impaired, while after stress further deterioration of performance was rescued by switching behavior increasingly to a stimulus-response strategy.


Age and disease severity predict choice of atypical neuroleptic: a signal detection approach to physicians' prescribing decisions.
We used a novel application of a signal detection technique, receiver operator characteristics (ROC), to describe factors entering a physician's decision to switch a patient from a typical high potency neuroleptic to a particular atypical, olanzapine (OLA) or risperidone (RIS). ROC analyses were performed on pharmacy records of 476 VA patients who had been treated on a high potency neuroleptic then changed to either OLA or RIS. Overall 68% patients switched to OLA and 32% to RIS. The best predictor of neuroleptic choice was age at switch, with 78% of patients aged less than 55 years receiving OLA and 51% of those aged greater than or equal to 55 years receiving OLA (chi(2)=38.2, P<0.001). Further analysis of the former group indicated that adding the predictor of one or more inpatient days to age increased the likelihood of an OLA switch from 78% to 85% (chi(2)=7.3, P<0.01) while further analysis of the latter group indicated that adding the predictor of less than 10 inpatients days to age decreased the likelihood of an OLA switch from 51% to 45% (chi(2)=7.0, P<0.01). ROC analyses have the advantage over other analyses, such as regression techniques, insofar as their "cut-points" are readily interpretable, their sequential use forms an intuitive "decision tree" and allows the potential identification of clinically relevant "subgroups". The software used in this analysis is in the public domain (http://mirecc.stanford.edu).


The pediatric foot and ankle.
MR imaging can be extremely helpful in evaluating congenital and acquired deformities of the foot and ankle. Knowledge of the normal developmental anatomy of the foot and ankle is important to accurately identify abnormalities versus normal variants. The foot and ankle may be abnormal because of trauma, infection, tumor, or systemic disease. MR imaging can help in the differential diagnosis of abnormalities as well as in treatment planning and follow-up.


Clinical and therapeutic applications of neuromuscular stimulation: a review of current use and speculation into future developments.
In this paper we present an overview of current research into clinical and therapeutic applications of electrical neuromuscular stimulation (NMS). As this is now such a huge subject we have focused our attention on the therapeutic rather than orthotic uses of stimulation and limited the field almost exclusively to upper limb applications in hemiplegia. The evidence that NMS influences motor re-learning and how this may be measured is discussed. We have identified the following as the three most important unresolved issues: 1) an understanding of how NMS modifies the interactions within the nervous system, 2) clinical effectiveness of NMS, and 3) inexpensive, simple to insert and reliable controllable implanted systems. We discuss recent research aimed at resolving these issues and based on this we make some suggestions for future research. To resolve these issues we propose: 1) neurophysiologic research into the mechanism through which NMS interacts with the nervous system; 2) large multicenter randomized controlled trials using rigorous methodology that compare different applications of NMs; 3) continued technical development that is closely linked to clinical applications.


Sleep anomalies in the chronic fatigue syndrome. A comorbidity study.
Polysomnographic findings were compared between a group of patients with the chronic fatigue syndrome (CFS; n = 49) and a matched healthy control (HC) group (n = 20). Sleep initiation and sleep maintenance disturbances were observed in the CFS group. The percentage of stage 4 was significantly lower in the CFS group. A discriminant analysis allowed a high level of correct classification of CFS subjects and HC. Sleep-onset latency and the number of stage shifts/hour contributed significantly to the discriminant function. The presence of these anomalies as well as the decrease in stage 4 sleep were not limited to the patients also diagnosed with fibromyalgia or with a psychiatric disorder. No association was found between sleep disorders and the degree of functional status impairment. The mean REM latency and the percentage of subjects with a shortened REM latency were similar in CFS and HC.


Analysis of host-inducing proteome changes in bifidobacterium longum NCC2705 grown in Vivo.
To investigate the molecular mechanisms underlying the adaptation of Bifidobacterium longum to the intestinal tract, we utilized a new model for rabbit intestinal culture of B. longum and reported the changes in proteomic profiles after incubation in the in vivo environment. By 2D-PAGE coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and/or electrospray ionization tandem mass spectrometry (ESI-MS/MS) analyses, proteomic profiles of B. longum strain NCC2705 grown in the in vivo and in vitro environments were compared. Confirmed by semiquantitative RT-PCR, which exhibited at least a 3-fold change or greater, 19 up-regulated proteins, 14 down-regulated proteins, and 4 proteins with mobility changes were identified during intestinal growth. These identified proteins include key stress proteins, metabolism-related proteins, and proteins related to translation. Our results indicate that some useful proteins are expressed at higher levels in cells during intestinal growth. These proteins reflected the adaptation of B. longum NCC2705 to the intestine, such as EF-Tu which contributes to the retention or attachment as a Bifidobacterium adhesin-like factor, bile salt hydrolase (BSH) which might play an important role in the molecular mechanisms for the initial interaction of probiotic with the intestinal environment, and stress proteins which defend B. longum against the action of bile salts and other harmful ingredients of the gastrointestinal tract (GIT). The most striking fact of our observation was that four proteins GlnA1, PurC, LuxS, and Pgk exhibit clear post-translational modification. Western blot (WB) analysis and Pro-Q Diamond staining revealed that substances of the GIT trigger Pgk and LuxS phosphorylation at Ser/Thr residues for bacteria grown in vivo. These proteins were identified for the first time as bifidobacterial phosphoproteins. Our data suggest that the phosphorylated autoinducer-2 production protein LuxS of B. longum NCC2705 (LuxS-P) is the active form of LuxS and that LuxS-P may play a key role in the regulation of quorum sensing.


Cord blood red cell osmotic fragility: a comparison between preterm and full-term newborn infants.
The osmotic fragility of red blood cells reflects their membrane ability to maintain structural integrity. The osmolality at which the cells lyse is related to their shape, deformability, surface area/volume ratio and intrinsic membrane properties. In cord blood, there may be differences between premature and term infants, and be influenced by maternal medication and other factors. There have been no definitive findings on possible differences between preterm and full-term infant osmotic fragility. To determine if cord blood erythrocyte osmotic fragility differs between premature and full-term newborn infants, using two parallel techniques. Cord blood samples were obtained from preterm singletons (N=11), preterm multiple births (N=10), full-term infants (N=24), as well as adults (N=22), for comparison. An osmotic fragility test was used to determine the NaCl concentration at which 20%, 50% and 80% of hemolysis occurred using individual logistic curves. A glycerol lysis test determined the time needed to lyse 50% of red blood cells. Cord blood red cells of multiple birth premature infants were more hemolysis-resistant than erythrocytes from full-term infants or adults. Another index of osmotic fragility, the difference in NaCl concentration for 80% and 20% red cell hemolysis showed that premature infants had greater differences than full-term infants or adults. Glycerol lysis time revealed that both preterm and full-term infants had an erythrocyte subpopulation that took longer than adult blood to attain 50% hemolysis. Correlation between both tests was very significant (r=-0.603, P<0.0001, N=67). This study shows that erythrocytes of premature infants, although, in average, less osmotically fragile than those of healthy full-term infants, contain a more hemolysis-susceptible cell subpopulation.


Inhibition of metastasis of syngeneic murine melanoma in vivo and vasculogenesis in vitro by monoclonal antibody C11C1 targeted to domain 5 of high molecular weight kininogen.
Metastasis of malignant tumors is a major cause of morbidity and mortality. Inhibition of tumor growth in distant organs is of clinical importance. We have demonstrated that C11C1, a murine monoclonal antibody to the light chain region of high molecular weight kininogen (HK), reduces growth of murine multiple myeloma in normal mice and human colon cancer in nude mice. C11C1 inhibits angiogenesis by reducing tumor microvascular density by blocking binding of HK to endothelial cells. We now evaluate the anti-metastatic effect of C11C1 on C57BL/6 mouse lung metastatic model using B16F10 melanoma cells. The tail veins of mice were injected with 0.5 × 10(6) cells of melanoma B16F10. One group received C11C1 and the other received saline (control) intraperitoneally. When mice were killed at 28 days, 6 of 10 control mice had detectable metastatic pulmonary nodules which stained positive with an antibody against S-100 protein, a tumor antigen present in malignant melanoma cells. In the C11C1 groups, none of the mice showed metastatic foci in their lungs. We showed that C11C1 inhibits endothelial cell tube formation in a 3-D collagen fibrinogen gel model by inhibiting the rate of cleavage of HK by plasma kallikrein without changing the binding affinity for HK. These studies demonstrate that a monoclonal antibody to HK has the potential to prevent metastasis with minimal side effects.


Oxidation of an o-iminobenzosemiquinone radical ligand by molecular bromine: structural, spectroscopic, and reactivity studies of a copper(II) o-iminobenzoquinone complex.
The bis(o-iminobenzosemiquinonato)copper(II) complex 1, containing the radical form [L(*)SQ](1-) arising from the aerial oxidation of the noninnocent ligand 2-anilino-4,6-di- tert-butylphenol, H2L, is readily oxidized by molecular bromine to a bis(o-iminobenzoquinone)copper(II) complex, 2. Thus, a ligand-based oxidative addition is reported for complex 1 containing an electron-rich Cu(II) d(9) metal ion. The crystal structure of the synthesized hexacoordinated complex [Cu(II)(LBQ)2Br2] (2) has been determined by X-ray crystallography at 100 K. Variable-temperature (2-290 K) magnetic susceptibility measurements and an X-band electron paramagnetic resonance spectrum establish the spin state to be St = 1/2 because of localized spin moments mainly in the (d(x(2)-y(2)))(1) orbital of a Cu(II) d(9) ion, indicating clearly the presence of a neutral iminobenzoquinone form, [LBQ](0), of the ligand in 2, as is found also in the X-ray structure. Electrochemical measurements (cyclic voltammograms and coulometry) indicate two successive one-electron reductions of the ligand. The reactivity of complex 2 as an oxidizing agent toward ethanol and triethylamine has been investigated.


Lead-Free Perovskite Nanowire-Employed Piezopolymer for Highly Efficient Flexible Nanocomposite Energy Harvester.
In the past two decades, mechanical energy harvesting technologies have been developed in various ways to support or power small-scale electronics. Nevertheless, the strategy for enhancing current and charge performance of flexible piezoelectric energy harvesters using a simple and cost-effective process is still a challenging issue. Herein, a 1D-3D (1-3) fully piezoelectric nanocomposite is developed using perovskite BaTiO3 (BT) nanowire (NW)-employed poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) for a high-performance hybrid nanocomposite generator (hNCG) device. The harvested output of the flexible hNCG reaches up to ≈14 V and ≈4 µA, which is higher than the current levels of even previous piezoceramic film-based flexible energy harvesters. Finite element analysis method simulations study that the outstanding performance of hNCG devices attributes to not only the piezoelectric synergy of well-controlled BT NWs and within P(VDF-TrFE) matrix, but also the effective stress transferability of piezopolymer. As a proof of concept, the flexible hNCG is directly attached to a hand to scavenge energy using a human motion in various biomechanical frequencies for self-powered wearable patch device applications. This research can pave the way for a new approach to high-performance wearable and biocompatible self-sufficient electronics.


Prognostic significance of estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and nm23 expression in patients with invasive breast cancer.
To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC). Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections. We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients. Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.


Increase in serum concentrations of inhibin in early onset pre-eclampsia with intrauterine growth restriction.
Recently, it has been hypothesized that reduced placental blood flow in early pregnancy causes changes in endothelial function, leading to pre-eclampsia. To clarify this clinically, we assessed serum concentrations of inhibin and uric acid in pre-eclamptic women compared with those of normotensive pregnant women. One hundred and forty normotensive pregnant women (at 20-41 weeks' gestation) and 50 women with pre-eclampsia (at 24-41 weeks' gestation) were the study subjects. Pre-eclamptic women were classified according to the new criteria for pregnancy-induced hypertension produced by the Japanese Society of Obstetrics and Gynecology (JSOG). Serum concentrations of uric acid and inhibin were measured enzymatically and by radioimmunoassay, respectively. Serum concentrations of inhibin and uric acid in the pre-eclamptic women were significantly higher than in gestational age-matched normotensive pregnant women. There were significant correlations among inhibin and uric acid, blood pressure and birth weight. According to JSOG criteria, of the 50 pre-eclamptic women, 18 were early onset (EO), including 16 cases complicated by intrauterine growth restriction (IUGR), and 32 cases were late onset, including 12 cases complicated by IUGR. In the patients with EO and IUGR, serum concentrations of inhibin, but not uric acid, were significantly elevated as compared with those of the other pre-eclamptic women. The results suggest that an increase in the serum concentration of inhibin seen in EO pre-eclampsia, together with IUGR, might be a cause of reduced placental blood flow.


Cost-effectiveness of the HiBalance training program for elderly with Parkinson's disease: analysis of data from a randomized controlled trial.
To determine the cost-effectiveness of the HiBalance training program for managing Parkinson's disease (PD)-related balance and gait disorders. Cost comparison design following the randomized controlled trial comparing a novel balance training intervention with care as usual. A total of 100 participants with mild-moderate PD were randomized to either the intervention ( n = 51) or the control group ( n = 49). A 10-week (three times per week), group-based, progressive balance training program, led by two physical therapists. All program costs were collected for both groups. Cost-utility was evaluated using quality-adjusted life years (QALYs) and cost-effectiveness measures were the Mini Balance Evaluation Systems Test (Mini-BESTest; assessing balance performance) and gait velocity. Incremental cost-effectiveness ratios were calculated and a probabilistic sensitivity analysis was conducted. The between-group difference in QALYs was 0.043 (95% confidence interval (CI): 0.011-0.075), favoring the intervention group. Between-group differences in balance performance and gait velocity were 2.16 points (95% CI: 1.19-3.13) and 8.2 cm/second (95% CI: 2.9-13.6), respectively, favoring the intervention group. The mean cost per participant in the intervention group was 16,222 SEK (€1649) compared to 2696 SEK (€274) for controls. The estimated incremental cost-effectiveness ratios were 314,558 SEK (€31,969) for an additional QALY, 6262 SEK (€631) for one point improvement in balance performance, and 1650 SEK (€166) for 1 cm/second increase in gait velocity. Sensitivity analyses indicated a high probability (85%) of program success. In terms of QALYs, the HiBalance program demonstrated a high probability of cost-effectiveness in the short-term perspective when considering the willingness-to-pay thresholds used in Europe.


Joint nested frailty models for clustered recurrent and terminal events: An application to colonoscopy screening visits and colorectal cancer risks in Lynch Syndrome families.
Joint models for recurrent and terminal events have not been yet developed for clustered data. The goals of our study are to develop a statistical framework for modelling clustered recurrent and terminal events and to perform dynamic predictions of the terminal event in family studies. We propose a joint nested frailty model for colonoscopy screening visits and colorectal cancer onset in Lynch Syndrome families. The screening and disease processes could each depend on individuals' screening history and other measured covariates and be correlated within families; our approach allows for familial correlations to affect both the visit process and the terminal event and the dependence between the two processes is specified through frailty distributions. We provide dynamic predictions of colorectal cancer risk for an individual conditional on his/her own screening history, his/her family history of screening and disease and other important clinical covariates. We apply our model to 18 Lynch Syndrome families from Newfoundland for individualized dynamic predictions of colorectal cancer risks. We demonstrate that the screening visits are non-ignorable for estimating the disease risks, and the joint nested frailty model improves dynamic prediction accuracies compared to existing joint frailty models after accounting for familial and individual screening and cancer histories.


Clinical relevance of terminal transferase and adenosine deaminase in leukemia.
Terminal Transferase (TdT), Adenosine Deaminase (ADA), immunological membrane markers, cytochemical reactivity and cytogenetics were analyzed in 226 patients with ALL, AUL and AML, in 70 patients with CML and in 3 cases of Ph' positive acute leukemia presenting as ALL. TdT was tested in peripheral blood and bone marrow with both the biochemical and immunofluorescence (IF) methods, and ADA was determined biochemically only in peripheral blood cells. By using conventional cytochemistry, cell surface markers determinations, TdT and ADA analysis, three distinct groups are recognized in ALL at presentation: T-ALL with TdT+ and very high ADA values; non-T, non-B ALL with TdT+ and intermediate levels of ADA; B-ALL with TdT absence and low levels of ADA. Clinical presentation and responses to therapy in adult and children ALL were correlated to TdT determinations. The median survivals in adults, calculated for TdT+ and TdT- groups, were 14.2 and 5.6 months, respectively. TdT and ADA were determined in ALL during remission. The wide fluctuation observed for TdT IF and ADA values prevented a reliable monitoring of remissions. At relapse, TdT and ADA values were similar to those found for ALL at presentation; TdT IF determinations were diagnostic in cases showing CNS involvement as the only localization. Forty per cent of AUL and 11% of AML cases were positive for TdT; the medians of ADA values of the TdT+ cases in both AML and AUL were several times higher than those obtained in the TdT- group. While TdT positivity and high ADA had a favorable prognostic value in AUL, similar conclusions can not be drawn at the moment for AML. In chronic phase of CML, TdT was strictly negative and ADA values were increased over the control line only in cases showing initial signs of transformation. In acute phase, the cases positive for TdT (32%) presented a significantly higher ADA activity than the TdT negative ones. The actuarial survival curves for the TdT+ and TdT- groups differ significantly, presenting median survivals from onset of phase of 11 and 4.8 months respectively. The three cases of Ph' positive ALL were all TdT+, presented high ADA values and entered chronic phase of CML after therapy.


Clinical application of the forearm tourniquet.
We undertook this prospective study of 148 consecutive hand and wrist procedures to evaluate the safety and efficacy of the forearm tourniquet. Patients were assigned to three groups based on tourniquet pressure used, ranging from 50 to 125 mmHg above systolic blood pressure. The forearm tourniquet was well tolerated by all patients. No patient had neurologic complications. Minimal intraoperative bleeding occurred when the pressure was greater than 75 mmHg above systolic blood pressure. The forearm tourniquet is a safe and effective means of providing a bloodless field for wrist and hand surgery.


Pressure effect on the rotator-II to rotator-I transition of alkanes.
We examine the effect of pressure on the rotator-II (R(II)) to rotator-I (R(I)) (R(II)-R(I)) transition within Landau phenomenological theory. The influence of pressure on the R(II)-R(I) transition is discussed by varying the coupling between the lattice distortion and the area/molecule. The pressure dependence of the area/molecule and the lattice distortion are calculated near the R(II)-R(I) transition. The R(II)-R(I) transition is found to be first order even at elevated pressure. The Landau coefficients are calculated from the experimental data. The theoretical results are in good agreement with available experimental results.


Decontamination of ultrasound equipment used for peripheral ultrasound-guided regional anaesthesia.
Portable ultrasound machines are frequently used in operating theatres for peripheral single-shot nerve block procedures. This equipment must be decontaminated by reducing the microbial load to a sufficient level to reduce the risk of nosocomial infection. In our institution we use a simple three-step decontamination protocol utilising 70% isopropyl alcohol as chemical disinfectant. We performed a prospective, quality assurance study to assess the efficacy of this protocol, as it is unclear if this is suitable for disinfecting semi-critical equipment. The primary endpoint was presence of microbial contamination prior to re-use of equipment. Over a four-week period, 120 swabs were taken from multiple sites on our ultrasound machines and linear array transducers for microbial culture. Swabs were taken after decontamination and immediately prior to patient contact. Any pathogenic and environmental bacterial organisms were isolated and identified. No pathogenic organisms were grown from any of the collected swabs. In 85% (n=102) of cultures, no growth was detected. Of the remaining 15% (n=18), commensal organisms commonly found on skin, oral and environmental surfaces were isolated. Our results suggest that our decontamination protocol may be an effective, rapid and cost-effective method of cleaning ultrasound equipment used for peripheral invasive single-shot nerve blocks. Further guidance from national bodies is required to define appropriate cleaning protocols for these machines.


Spontaneous cutaneous endometriosis in the mons pubis region: a case report diagnosed by fine-needle aspiration biopsy.
Most cutaneous endometriosis develops at the site of an abdominal surgical scar. Spontaneous cutaneous endometriosis is extremely rare. We report a case of spontaneous cutaneous endometriosis in the mons pubis region. A 41-year-old woman presented with a mass in the right mons pubis, causing cyclic pain associated with menses. Fine-needle aspiration (FNA) biopsy was performed. The smears contained three cellular components: honeycombed sheets of glandular epithelial cells, fragments of ovoid-to-spindle shaped stromal cells, and background inflammatory cells, including hemosiderin-laden macrophages, histiocytes, and neutrophils. Biphasic clusters of glandular epithelial cells and stromal cells were identified. FNA cytology is a safe and useful adjunctive tool for diagnosing cutaneous endometriosis.


Modulation of brain dopamine transmission by sex steroids.
Sex steroid hormones influence the dopaminergic systems of the hypothalamus as well as the extrahypothalamic regions of the brain in controlling movement and behavior in both humans and animals. This review focuses on the effects of sex steroids on dopaminergic activity in extrahypothalamic brain areas. Among sex steroids, estrogens have been most extensively investigated, and many studies report that estrogens affect behaviors mediated by the basal ganglia, such as in humans suffering from extrapyramidal disorders. Epidemiological and clinical evidence also suggests an influence of estrogens on the vulnerability threshold for schizophrenia and sex differences in the clinical expression of this disease. Clinical observations point to a role of androgenic hormones in Gilles de la Tourette's syndrome. In normal humans, sex steroids were also shown to influence motor and cognitive performance. Biochemical and behavioral studies in animals have also shown the effect of sex steroids on dopaminergic activity in the basal ganglia; however, both activating and inhibiting effects have been reported. This may partly be explained by effects of the dose, duration of treatment, interval between steroid administration and testing the behavior measured, and the part of the basal ganglia from which the behavior is elicited. In view of the numerous variables that influence net dopaminergic response to steroids, focus will be on the literature using similar experimental conditions to assess the effect of in vivo chronic steroid treatment, acute short-term steroid treatment and the estrous cycle as well as in vitro effects of steroids on dopamine receptors. These experimental paradigms point to two general mechanisms of action of steroids: a rapid short-term non-genomic membrane effect and a slower long-term possibly genomic effect of steroids on dopamine systems. Combining dopaminergic drugs with sex steroids could improve efficacy or reduce side effects associated with these drugs. Examples of such combined treatments in rats and monkeys are presented for delta 9-tetrahydrocannabinol, cocaine, neuroleptics, apomorphine and L-DOPA. A better understanding of steroid-dopamine interactions and the possible isolation of conditions to have only pro or anti dopaminergic activity could then be used to develop combined therapies or to optimize drug treatments that would take into account the patient's sex and endocrine status.


Associations between social behaviour and adrenal activity in female Barbary macaques: consequences of study design.
Faecal glucocorticoid metabolite (fGCM) concentrations have been used to evaluate adrenal activity in a variety of species; including as an indicator of the physiological response to social stress. However, across studies, the relationships between dominance rank, social behaviours and adrenal responses can be inconsistent. Differences in the relationship between rank and glucocorticoids may be due to the relative costs of social status, and the relative frequencies of social stressors and potential coping mechanisms. However, the differences in observed relationships between specific social behaviours and glucocorticoids may be partly explained by sampling frequency, as studies often use average fGCM concentrations collected over a period of weeks or months, rather than fGCM concentrations that are temporally-matched with behavioural data. In this study, we directly compared long-term average and temporally-matched data to determine whether particular social behaviours were related to adrenal activity in female Barbary macaques (Macaca sylvanus) at Trentham Monkey Forest, UK; and whether observed relationships were consistent using these two approaches. Average rates of autogrooming were positively correlated with average fGCM; however, this relationship was not robust in temporally-matched samples. Instead, specific social behaviours associated with agonism were associated with fGCM in temporally-matched samples within individuals. These results indicate that analyses of relationships using long-term average fGCM and temporally-matched samples do not necessarily provide comparable results, highlighting that study design is critical in determining associations between an individual's social behaviour and the relative physiological costs involved.


Postmortem distribution of trazodone concentrations.
Non-toxic postmortem trazodone tissue (liver) concentrations have not been previously described. Liver trazodone concentrations were compared to peripheral blood and central blood concentrations in 19 medical examiner cases. Postmortem blood specimens were initially screened for alcohol and simple volatiles, drugs of abuse, and alkaline drugs. Trazodone, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a high performance liquid chromatography procedure. Re-analyses showed that there may be degradation of trazodone in postmortem blood stored at 4°C. There was, on average, about a 20% decrease in samples stored up to eight months. These data suggest that postmortem trazodone peripheral blood concentrations may be considered non-toxic to at least 1.0mg/L with liver concentrations to at least 2.2mg/kg. Overall, trazodone concentrations ranged from 0.08-6.1mg/L in peripheral blood, 0.07-7.1mg/L in central blood, and 0.39-26mg/kg in liver. The median trazodone central blood to peripheral blood ratio was 0.98 (N=19). The liver to peripheral blood ratios showed a median value of 2.8L/kg (N=18). Given that a liver to peripheral blood ratio less than 5L/kg is consistent with little to no propensity for postmortem redistribution, these data demonstrate that trazodone is unlikely to show significant redistribution.


A signal network involving coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCL-XL expression and promotes cell survival of head and neck squamous cell carcinomas.
Abrogation of apoptosis to sustain cell survival is an essential step in development of cancer. Aberrant activation of signal transcription factors NF-kappaB or STAT3, alterations in p53 status, or BCL/BAX family expression have each been reported to affect cell survival in cancer, including head and neck squamous cell carcinomas (HNSCC). However, molecular targeting of these alterations individually has yielded disappointing results. In our study, we examined the hypothesis that alterations in a signal network involving NF-kappaB, STAT3 and p53 modulates expression of proapoptotic BAX and antiapoptotic BCL-XL proteins, and promotes cell survival of HNSCC. We found that NF-kappaB and STAT3 are coactivated together, and with cytokine stimulation or siRNA knock-down, both modulate BAX/BCL-XL. Greater modulation among HNSCC lines expressing low wt p53 than those over-expressing mt p53 protein suggested that decreased p53 expression might enhance activation of NF-kappaB, STAT3 and BCL-XL. Reexpression of wt p53 suppressed NF-kappaB and STAT3 nuclear binding activity, and BCL-XL expression, while inducing p21 and BAX. Over-expression of p53 together with inhibition of NF-kappaB or STAT3 induced greater increase in the BAX/BCL-XL ratio and apoptosis than modulation of these transcription factors individually. Conversely, NF-kappaB or STAT3 inducing cytokines decreased the BAX/BCL-XL ratio. Thus, a network involving signal coactivation of NF-kappaB and STAT3, differentially modified by p53 inactivation or mutation, promotes altered BAX/BCL-XL expression and cell survival in HNSCC. Inhibition of signal activation of both NF-kappaB and STAT3 together with reexpression of p53 could be the most effective strategy to restore BAX/BCL-XL regulation and for cytotoxic therapy of HNSCC.


Responsiveness of two methods for measuring foot and ankle volume.
Measurements of volume are taken in the clinical environment to determine the extent of swelling and to evaluate the effects of treatment interventions. In the research setting, volume measurements are taken to determine experimental outcomes. Water displacement and figure-of-eight methods are highly reliable for measuring foot and ankle volumes, but the responsiveness of the two methods has not been compared. This study was designed to investigate effects of manipulating hydrostatic and blood pressures on foot and ankle volume and responsiveness of the two methods to induced changes in foot and ankle volume. Intervention effects on volume were compared using water displacement and tape (figure-of-eight) methods. Foot and ankle volume was measured in each of the 30 participants while they were supine, sitting, and sitting with a sphygmomanometer cuff inflated around the lower thigh to occlude blood flow into the leg. These variations allowed manipulation of the hydrostatic and blood pressures acting on the foot and ankle. Data from the water displacement method showed that a significant increase in volume of 31 mL (p < 0.002) occurred with the cuff in place, but this was not detected using the figure-of-eight method. No significant difference (p > 0.136) between the sitting and supine positions was detected using either method. Limb dependency while sitting or lying had no effect on measures from either method, but volumetry had a higher responsiveness to changes induced by application of the cuff. This effect was interpreted as arterial leakage past the cuff. The figure-of-eight tape method and the water displacement technique for measuring ankle and foot volume may not be interchangeable. Changes in volume of the ankle and foot are better measured by the water displacement technique, but for measurements of ankle volume alone, the tape method is appropriate. The responsiveness of the tape method to changes in volume is yet to be determined.


Effect of resonator length on a doubly resonant optical parametric oscillator pumped by a multilongitudinal-mode beam.
The resonator length of an optical parametric oscillator (OPO) is normally made a short as possible to minimize the signal-buildup time and maximize the output energy. We have found that, when a doubly resonant OPO is pumped by a multilongitudinal-mode beam, its output energy has a significant maximum when its optical length matches that of the pump source, even if this length is much greater than the shortest possible for the OPO. We have observed this effect in a ZnGeP>(2)-based OPO and reproduced it in numerical simulations.


Time-dependent density functional theory investigation of electric field effects on absorption spectra of meso-meso-linked zinc porphyrin arrays: Role of charge-transfer States.
By using time-dependent density functional theory, we calculated the transition energies of a zinc porphyrin monomer and its meso-meso-linked arrays. In line with the prediction of the molecular exciton model, the calculated splitting energy of the Soret band increased as the number of linked porphyrins increased. We then examined how the transition energies of the dimer array were shifted by an applied electric field. For reproduction of an electroabsorption spectrum (EA), i.e., the field-induced change in absorption intensity, a model Hamiltonian constructed from five states is proposed. It is concluded for the dimer that the field-induced coupling between the lower-energy Soret band Se and the lower-lying ionic character (charge-transfer) states is responsible for the experimentally observed blue shift of Se as well as the second-derivative profile in the EA spectrum.


Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers.
Metabolism and excretion of erlotinib, an orally active inhibitor of epidermal growth factor receptor tyrosine kinase, were studied in healthy male volunteers after a single oral dose of [14C]erlotinib hydrochloride (100-mg free base equivalent, approximately 91 microCi/subject). The mass balance was achieved with approximately 91% of the administered dose recovered in urine and feces. The majority of the total administered radioactivity was excreted in feces (83+/-6.8%), and only a low percentage of the dose was recovered in urine (8.1+/-2.8%). Only less than 2% of what was recovered in humans was unchanged erlotinib, which demonstrates that erlotinib is eliminated predominantly by metabolism. In plasma, unchanged erlotinib represented the major circulating component, with the pharmacologically active metabolite M14 accounting for approximately 5% of the total circulating radioactivity. Three major biotransformation pathways of erlotinib are O-demethylation of the side chains followed by oxidation to a carboxylic acid, M11 (29.4% of dose); oxidation of the acetylene moiety to a carboxylic acid, M6 (21.0%); and hydroxylation of the aromatic ring to M16 (9.6%). In addition, O-demethylation of M6 to M2, O-demethylation of the side chains to M13 and M14, and conjugation of the oxidative metabolites with glucuronic acid (M3, M8, and M18) and sulfuric acid (M9) play a minor role in the metabolism of erlotinib. The identified metabolites accounted for >90% of the total radioactivity recovered in urine and feces. The metabolites observed in humans were similar to those found in the toxicity species, rats and dogs.


Neurotrophin receptor expression in retrogradely labeled trigeminal nociceptors--comparisons with spinal nociceptors.
In situ hybridization for trkA mRNA in trigeminal ganglion neurons retrogradely labeled with FluoroGold from the mandibular incisor demonstrated limited expression of the high-affinity nerve growth factor (NGF) receptor in this presumptive nociceptor population. Immunocytochemistry using polyclonal anti-trkA antibodies confirmed this result and extended it to show low levels of trkA protein expression in afferents labeled from the cornea. Less than 10% of the cells innervating the incisor, and approximately 15% of those innervating the cornea, were trkA-positive in adult and neonatal mice. This proportion is considerably lower than that observed in Dorsal Root Ganglion nociceptors, in which approximately 80% in neonates and approximately 40% in adults express trkA (Molliver and Snider, J. Comp Neurol 381: 428-438, 1997). Presumptive trigeminal nociceptors were further identified on the basis of expression of Calcitonin gene related peptide. In the entire ganglion, approximately 43% of the trkA-positive cells were CGRP-positive, and approximately 44% of the CGRP-positive cells were trkA-positive. Most trkA-positive cells that were CGRP-negative were medium-to-large diameter, while most of those that were CGRP-positive but trkA-negative were small diameter. Only approximately 5% of trkA-positive cells labeled from the incisor, and approximately 10% from the cornea, were CGRP-positive. Approximately 15% of the corneal or pulpal afferent neurons expressed ret-immunoreactivity. These results suggest that trigeminal nociceptors differ from spinal nociceptors in several significant ways. Differences in neurotrophic requirements may be related to differences in target tissues, in embryonic origin of some trigeminal ganglion cells, or in the timing of down-regulation of trkA expression in trigeminal ganglion cells.


Japanese Gastric Cancer Association Task Force for Research Promotion: clinical utility of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography in gastric cancer. A systematic review of the literature.
Since April 2010, the Japanese Public Health Insurance System has covered the costs incurred for performing ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) imaging for patients with advanced gastric cancer. The aim of this review was to evaluate the clinical impact of PET for patients with gastric cancer. A systematic literature search was performed in PubMed/MEDLINE using the keywords "gastric cancer" and "PET" to search for relevant articles published from January 2000 to September 2010. The clinical impact of selected articles was assessed by the authors to evaluate the following: (a) tumor staging, (b) diagnosis for recurrent disease, (c) evaluation of treatment response, and (d) screening for gastric cancer. FDG uptake increases in papillary adenocarcinoma, tubular adenocarcinoma, and solid-type poorly differentiated adenocarcinoma. This uptake is also associated with glucose transporter 1 expression. The sensitivity and specificity of FDG-PET for metastatic lymph node detection were 21-40% and 89-100%, respectively. The sensitivity and specificity for distant metastasis detection were 35-74% and 74-99%, respectively. Treatment response can be detectable at an earlier stage by PET than by computed tomography (CT), because FDG uptake by cancer cells decreases according to the treatment response. In summary, although PET has limitations such as frequent false-negative cases in signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma, it can contribute to the selection of a more appropriate treatment modality by detecting distant metastases and treatment response.


Media Effects in Youth Exposed to Terrorist Incidents: a Historical Perspective.
This paper reviews the evidence on the relationship between contact with media coverage of terrorist incidents and psychological outcomes in children and adolescents while tracing the evolution in research methodology. Studies of recent events in the USA have moved from correlational cross-sectional studies examining primarily television coverage and posttraumatic stress reactions to longitudinal studies that address multiple media forms and a range of psychological outcomes including depression and anxiety. Studies of events in the USA-the 1995 Oklahoma City bombing, the September 11 attacks, and the 2013 Boston Marathon bombing-and elsewhere have used increasingly sophisticated research methods to document a relationship between contact with various media forms and adverse psychological outcomes in children with different event exposures. Although adverse outcomes are associated with reports of greater contact with terrorism coverage in cross-sectional studies, there is insufficient evidence at this time to assume a causal relationship. Additional research is needed to investigate a host of issues such as newer media forms, high-risk populations, and contextual factors.


[[111In]-DTPA-D-phenylalanine octreotide SPECT for the scintigraphic imaging of enhanced somatostatin-receptor density in endocrine ophthalmopathy].
Recently, [111In]-DTPA-D-phenylalanine-octreotide was introduced for clinical use. This radioligand binds specifically to somatostatin receptors and is suitable for SPECT examinations. The aim of this study was to clarify whether an increased somatostatin receptor density can be imaged and quantified in patients with endocrine ophthalmopathy (e.o.). 7 patients between 34 and 55 years with e.o. at stages III to VI and 4 controls between 38 and 63 years were examined. All patients and controls received approximately 200 MBq [111In]-DTPA-D-phenylalanine-octreotide by IV injection. A SPECT examination was performed 4 hours after injection and a normalised tracer uptake (A(n)) was calculated for both orbitae. In patients with e.o. the values of A(n) were significantly higher compared with controls (P = 0.002). There was a correlation between A(n) and exophthalmus stages according to Hertel with r = 0.844 (P = 0.001). These results indicate that [111In]-DTPA-D-phenylalanine-octreotide SPECT might be useful for the in vivo assessment of an increased somatostatin receptor density in e.o. These findings could have an impact on the treatment with somatostatin analogous in e.o.


An absorbable intravasal stent and a silicone intravasal reversible plug. Report of experiments on animals.
The high failure rate of vasovasotomy to restore fertility in vasectomized men prompted this investigation using guinea pigs as the experimental animals. The vasa were divided and absorbable intravasal stents were inserted into the lumens of the vasa at the site of anastomosis. The success or failure to secure patency and reestablish fertility was appraised by histologic sections, vasograms, semen analyses, and breeding tests. A second group of animals had silicone plugs equipped with a detachable central pin placed in both vasa. The design of this procedure was to produce an occlusive azoospermia which might be reversed by removing the central pin. Similar tests were used to establish the effectiveness of this reversible device in producing a temporary sterilization. The procedures were controlled by sham operations and insertion of plugs without pins.


Integration of three-dimensional corticospinal tractography into treatment planning for gamma knife surgery.
In the radiosurgical treatment of critically located lesions, the effort to minimize the risk of complication is essential. In this study the integration of diffusion-tensor (DT) imaging-based tractography was clinically applied to treatment planning for gamma knife surgery (GKS). Seven patients with cerebral arteriovenous malformations located adjacent to the corticospinal tract (CST) underwent this technique. Data provided by DT imaging were acquired before the frame was affixed to the patient's head and the CST of the DT tractography was created using our original software. Stereotactic three-dimensional imaging studies were obtained after frame fixation and then coregistered with the data from DT tractography. After image fusion of the two studies, the combined images were transported to a GKS treatment-planning workstation. The spatial relationship between the dose distribution and the CST was clearly demonstrated within the 2 hours it took to complete the entire imaging process. The univariate logistic regression analysis of transient or permanent motor complications revealed a significant independent correlation with the volume of the CST that received 25 Gy or more and with a maximum dose to the CST (p < 0.05). The integration of DT tractography into the GKS treatment planning was highly useful in confirming the dose to the CST during treatment planning.


Quantification of animal fat biodiesel in soybean biodiesel and B20 diesel blends using near infrared spectroscopy and synergy interval support vector regression.
In this work, multivariate calibration based on partial least squares (PLS) and support vector regression (SVR) using the whole spectrum and variable selection by synergy interval (siPLS and siSVR) were applied to NIR spectra for the determination of animal fat biodiesel content in soybean biodiesel and B20 diesel blends. For all models, prediction errors, bias test for systematic errors and permutation test for trends in the residuals were calculated. The siSVR produced significantly lower prediction errors compared to the full spectrum methods and siPLS, with a root mean squares error (RMSEP) of 0.18%(w/w) (concentration range: 0.00%-69.00%(w/w)) in the soybean biodiesel blend and 0.10%(w/w) in the B20 diesel (concentration range: 0.00%-13.80%(w/w)). Additionally, in the models for the determination of animal fat biodiesel in blends with soybean diesel, PLS and SVR showed evidence of systematic errors, and PLS/siPLS presented trends in residuals based on the permutation test. For the B20 diesel, PLS presented evidence of systematic errors, and siPLS presented trends in the residuals.


Aldosterone, not estradiol, is the physiological agonist for rapid increases in cAMP in vascular smooth muscle cells.
Steroid-induced gene regulation in the endocrine tissues and vascular wall is achieved through the interaction of specific receptor proteins and promoters of target genes. In addition to these delayed steroid actions, rapid effects of steroids have been reported in various tissues that were clearly incompatible with the classic theory of genomic steroid action. Because high doses of 17beta-estradiol have been shown to modulate intracellular cAMP levels in vascular smooth muscle cells, steroid-induced stimulation of adenylate cyclase stimulation and phosphorylation of cAMP response element binding protein was investigated in porcine coronary artery vascular smooth muscle cells. Aldosterone induces a approximately 1.5- to 2.5-fold increase in intracellular cAMP levels (EC50 approximately 0.01 to 0.1 nmol/L) within 1 minute, whereas 17beta-estradiol and hydrocortisone act only at supraphysiological concentrations (10 micromol/L). Aldosterone-induced changes in intracellular cAMP are calcium dependent; they are not blocked by inhibitors of mineralocorticoid receptors, transcription, or protein synthesis. In addition, aldosterone induces a time-dependent phosphorylation of cAMP response element binding protein with potential transcriptional importance. A nongenomic modulation of vascular smooth muscle cells by aldosterone is consistent with the data that aldosterone, not estrogen, is the physiological stimulus for cAMP.


Facing type 2 diabetes in the healthcare reform era.
One of the greatest challenges facing healthcare systems today is the management of chronic disease. Patients with chronic diseases often require multiple medications, frequent physician visits and monitoring, and even hospitalization. Diabetes is one of the most prevalent chronic conditions in the United States, affecting over 20 million Americans. Diabetes causes significant morbidity and mortality and places a tremendous strain on the American healthcare system. One of the greatest contributing factors to the increase in diabetes prevalence is the increased incidence of obesity; in 2000, almost 20% of Americans were considered obese. In order to fight the growing prevalence of diabetes, numerous guidelines and consensus statements have been issued to lay the groundwork for the management and prevention of this chronic disease. Despite these efforts, significant barriers remain. These barriers may only be overcome through significant change within the healthcare system. Value-based insurance design is one method that has the potential to bring about the necessary change to fight chronic diseases such as diabetes. Further investigation of clinical practice and payer models is necessary to resolve some of the interrelated clinical and economic issues associated with its implementation.


[Comorbid depression in patients with epilepsy treated with single and multiple drug therapy].
A seizure is a disturbance of movement, feeling or consciousness occasioned by sudden, inappropriate and excessive electrical discharges in the grey matter of the brain. The most common psychiatric disorder in epilepsy is interictal depression, with lifetime prevalence of 40 to 60%. Particular attention should be paid to suicidal ideations, due to the fact that most of the patients have easy access to potentially lethal when overdosed, antiepileptic drugs. The aim of our paper is to determine the presence of depressive symptoms in epileptic patients according to their treatment protocols (monotherapy or polytherapy), gender, age, social status, age when diagnosed, type and frequency of seizures. Prospective evaluation of monotherapy and polytherapy in 60 subjects, (30 subjects in each group), who were diagnosed with epilepsy. Assessment of depressive symptoms was performed with the use of BDI scale. In both groups there was a similar structure according to gender, mean age was 34 (with an s.d. of 11.06). More than 96 percent of the subjects had low or average socioeconomic status. Average age of first attack was 20.43 (with an s.d. of 11.9). In the group treated with monotherapy there was the biggest number of generalized convulsive seizures, and in the group treated with polyantiepileptic therapy there was the biggest number of partial complex seizures. Symptoms of moderate and severe depression were registered in 33% patients treated with monotherapy and 60% of patients treated with polytherapy (t = 2.198, for p less than 0.05). 16.7 percent of the patients had suicidal ideation. On the basis of our research we can conclude that significantly more frequent and severe depressive symptoms were found in the group of epileptic patients who were treated with polytherapy. In those patients the occurrence of partial complex seizures was the biggest, and their frequency was weekly or even daily.


[Efficacy of physical training and types of hemodynamics of essential hypertension patients and healthy subjects].
Physical stress tolerance and the effect of swimming-pool exercise were examined in patients with essential hypertension (EH) and normal untrained subjects with respect to their hemodynamic types. Threshold load capacity at bicycle ergometry and the amount of swimming-pool exercise were lower in EH patients and normal individuals with hypokinetic circulation, as compared to other hemodynamic types. Insufficient dilatation of the precapillary channel during exercise may be implicated here. In patients with stable EH and hypokinetic hemodynamics, exercise should be less intensive.


Perkinsus mediterraneus n. sp., a protistan parasite of the European flat oyster Ostrea edulis from the Balearic Islands, Mediterranean Sea.
A new species, Perkinsus mediterraneus, a protistan parasite of the European oyster Ostrea edulis (L.), farmed along the coast of the Balearic Islands, Mediterranean Sea, is described. Morphological examinations with light and transmission electron microscopy, DNA sequence-analysis and enlargement in Ray's fluid thioglycollate medium (RFTM) confirmed that this parasite belongs to the genus Perkinsus. Specific morphological and genetic characteristics indicated that it should be considered a new species in the genus. Sequencing of the small subunit ribosomal (ssu rRNA) gene confirmed that the parasite belongs to the genus Perkinsus, and sequences of the internal transcribed spacer (ITS) were distinct from any Perkinsus ITS sequences previously published and/or deposited in the GenBank. Phylogenetic analysis revealed that the ITS sequences of the new species formed a monophyletic group comprising a sister clade to the P. atlanticus/olseni group. In addition, morphological differences were observed between the new species and the other described Perkinsus spp.. After incubation in RFTM for 1 wk, the prezoosporangium had reached an extremely large size (97.4 +/- 1.99 microm) (mean +/- SE), and after 2 wk incubation had again almost doubled in size (167.1 +/- 8.09 microm). The discharge-tube length was one sixth the diameter of the zoosporangium, i.e. a ratio of 17.36:97.38, the lowest ratio observed for any Perkinsus species. At the ultrastructural level, zoosporangia and zoospores exhibited some differences compared to other Perkinsus species.


Physique and performance for track and field events.
Evidence of the importance of physique in the athletics disciplines is supported by the persistence of certain characteristics over long periods, despite marked secular changes in the source population. These characteristics may also result in physiological benefits such as effective thermoregulation or a greater power-to-weight ratio. Coaches and athletes are often convinced of weight or fat loss benefits based on personal or anecdotal experience, intuition, and "trained eye" observation of successful competitors. This may entice athletes into adopting unbalanced, erratic or highly restrictive eating patterns that increase the risk for nutrient deficiencies, and disordered eating. Despite heavy training loads and often extreme diets, some athletes fall short of their physique goals as ultimately phenotype is under genetic control. Professionals assisting athletes with physique management need to be highly skilled in anthropometry and require a thorough understanding of sports-specific nutrition requirements. Careful assessment of the risks and benefits of various approaches to weight and fat loss is required before they are recommended to athletes.


[Multifocal fractures of the mandibular symphysis. Apropos of 3 cases].
Three patients presented with multiple site fractures of mandibular symphysis, associated in two cases with a bilateral subcondylar fracture. Treatment was by multiple solid osteosynthesis of mandibular body combining miniaturized screw plates and steel wire osteosynthesis. Emphasis is placed on the interest of a stable solid osteosynthesis of mandibular symphysis by screw plate, combined with osteosynthesis using a steel wire passing through the hole of a plate and into the small basilar bone fragment, allowing in this way the restitution of a perfect morphology of symphysis.


Prediction of the utility of a switch from unilateral to bilateral ECT in the elderly using treatment 2 ictal EEG indices.
The choice of whether to administer nondominant unilateral (UL) or bilateral (BL) ECT remains controversial. A study in which moderately suprathreshold UL nonresponders at treatment 6 were randomized to UL or BL ECT offered the opportunity to explore whether ictal EEG indices at treatment 2 might predict response to UL ECT, and also which UL ECT nonresponders are likely to respond to BL ECT. We found that less postictal suppression in response to the second UL ECT stimulus was predictive of a poorer subsequent therapeutic response to UL ECT, but of a better therapeutic response if switched to BL ECT. A multivariate ictal EEG model was developed that had a significant capacity to differentiate those who will respond to UL ECT versus those who will not respond to UL ECT, but who will be therapeutic responders when switched to BL ECT. This study raises the possibility that ictal EEG indices at treatment 2 may identify situations when UL ECT is physiologically and therapeutically inadequate, and when BL ECT is likely to be more effective. The determination of whether such predictive physiologic models are of clinical utility for the prediction of outcome awaits further study.


Transcultural aspects of eating disorders: a critical literature review.
A review of studies addressing anorexia nervosa and bulimia nervosa among Native Americans, African-Americans, Hispanics, Asians, Africans, and Middle Easterners yielded only 35 studies, of which 22 were qualitative case reports, three were clinical quantitative studies, and ten were non-clinical quantitative studies. The case studies reported symptoms similar to those of Caucasian patients, and eating disorders were reported in all SES classes. The clinical studies, all reported from Asian countries, described a number of cases for eating disorders quite different from one another. The non-clinical quantitative studies reported a number of cases consistent with the ranges previously reported for controlled samples of non-clinical Caucasian populations. We found few or no quantitative studies on eating disorders from Hispanic, Middle Eastern, African, or Asian countries other than Japan.


Patterned Au/poly(dimethylsiloxane) substrate fabricated by chemical plating coupled with electrochemical etching for cell patterning.
In this paper, we present a novel approach for preparing patterned Au/poly(dimethylsiloxane) (PDMS) substrate. Chemical gold plating instead of conventional metal evaporation or sputtering was introduced to achieve a homogeneous gold layer on native PDMS for the first time, which possesses low-cost and simple operation. An electrochemical oxidation reaction accompanied by the coordination of gold and chloride anion was then exploited to etch gold across the region covered by electrolyte. On the basis of such an electrochemical etching, heterogeneous Au/PDMS substrate which has a gold "island" pattern or PDMS dots pattern was fabricated. Hydrogen bubbles which were generated in the etching process due to water electrolysis were used to produce a safe region under the Pt auxiliary electrode. The safe region would protect gold film from etching and lead to the formation of the gold "island" pattern. In virtue of a PDMS stencil with holes array, gold could be etched from the exposed region and take on the PDMS dots pattern which was selected to for protein and cell patterning. This patterned Au/PDMS substrate is very convenient to construct cytophobic and cytophilic regions. Self-assembled surface modification of (1-mercaptoundec-11-yl)hexa(ethylene glycol) on gold and adsorption of fibronectin on PDMS are suitable for effective protein and cell patterning. This patterned Au/PDMS substrate would be a potentially versatile platform for fabricating biosensing arrays.


Is there a role for circulating tumor cells in the management of breast cancer?
Circulating tumor cells (CTC) can be identified and characterized in blood of patients with many solid tumors, particularly breast cancer. Between 10% and 30% of patients with stage I to III breast cancer and 50% to 70% of women with metastatic breast cancer have detectable CTCs. In both cases, presence and elevation of CTCs are associated with worse prognosis. In the metastatic setting, persistent CTC after 3 to 5 weeks of a new therapy seem to indicate lack of activity of that regimen, and an ongoing prospective randomized clinical trial is addressing the relative worth of changing to an alternative treatment rather than waiting for classic clinical and radiologic evidence of progression. Recent technical advances offer the promise of further genotyping and phenotyping for important tumor-associated genes and proteins.


Pemetrexed ameliorates experimental arthritis in rats.
Pemetrexed (PMTX) is an anti-folate drug as methotrexate. The purpose of this study was to assess the efficacy of PMTX on collagen-induced arthritis (CIA). Forty Wistar albino rats were randomized into four groups. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant. Animals were sacrificed at the 15th day after the onset of arthritis. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and malondialdehyde (MDA) levels were increased, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were decreased in the arthritis group. In the PMTX-treated (0.2 and 1 mg/kg/week i.p.) groups, the levels of TNF-α, IL-17, and MDA were decreased; the activities of SOD, CAT, and GPx and the expressions of Nrf2 and HO-1 were restored, and perisynovial inflammation and cartilage-bone destruction were decreased. PMTX has anti-arthritic potential in the CIA model and may be a therapeutic agent for rheumatoid arthritis.


Prevalence of musculoskeletal disorders among paramedics working in a large hospital in Ahwaz, southwestern Iran in 2010.
Musculoskeletal disorders (MSDs) are common among employees throughout the world, particularly in high risk groups such as nurses. To determine the prevalence of MSDs among nurses in a large hospital in Ahwaz, southwestern Iran, and to examine its correlation with gender, age, shift working, years at service and smoking. Using a self-reported questionnaire-based cross-sectional study, Nordic questionnaire for MSDs was disseminated to all inpatient hospital paramedics (n = 195) in a large hospital in Ahwaz. Questionnaires of 161 participants were completed and returned back for analysis (response rate of 83%). The reported prevalence of MSDs was very high in the studied paramedics so that more than 90% of them reported at least one MSD in last week. The most prevalent site affected was that of neck (64%) followed by head (62.1%), knees (54.7%) and wrists/hands (49.7%); the least frequent disorder was that of elbows (14.3%). MSD was more common in females and increased with age and years of service. Non-shift workers reported more neck and elbows MSDs than shift workers. Considering the very high prevalence of MSDs among paramedics, it is suggested that they engage in an exercise program at their work place to lower the risk of MSDs and promote working efficiency.


Testing of the assumptions made in estimating the extent of futile cycling.
In estimating glucose and fructose 6-phosphate futile cycling in vivo, complete detritiation of [2-3H]glucose is assumed at the glucose 6-phosphate level, [3-3H]glucose at triose phosphate formation, and [6-3H]glucose in its conversion to glucose via pyruvate. [3-3H]glucose detritiation via the pentose cycle is assumed to be negligible. Normal and non-insulin-dependent diabetic subjects, in the basal state and infused with glucose, were given [2-3H,2-14C]galactose, and 3H-to-14C ratios in blood glucose were determined. [2-3H,2-14C]glucose was given with acetaminophen, and 3H/14C in urinary glucuronide was determined. Detritiation at glucose 6-phosphate was approximately 80%. [3-3H,1-14C]fructose was infused, and 3H/14C was determined in blood glucose and urinary glucuronide. At triose phosphate, 75-90% of the 3H was removed. The pentose cycle contribution was only a few percent. [6-3H,6-14C]glucose was infused, and 3H/14C in blood lactate was determined. [3-3H,3-14C]lactate was infused, and ratios in blood glucose were determined. Maximally, 10% of 3H from [6-3H]glucose was retained. If glucose and galactose are metabolized in the same hepatic site(s), glucose conversion to three-carbon intermediates in the indirect pathway of glycogen formation occurs in extrahepatic tissue(s). Reported estimates of futile cycling, although qualitatively correct, quantitatively require correction.


Hydrolysis of neutral glycerides by lipases of rat brain microsomes.
The hydrolysis of monoacylglycerol and diacylglycerol by rat brain microsomes was followed by measuring the release of glycerol and monooleylglycerol from dispersions of water insoluble glyceryl esters of oleic acid. The microsomes showed three lipolytic activities. One activity, optimal at pH 4.8, catalyzed the hydrolysis of diacylglycerol but not monoacylglycerol. Two other lipolytic activities, optimal at pH 8.0-8.6, catalyzed the hydrolysis of both diacylglycerol and monoacylglycerol. The pH 8.0-8.6 activities were sensitive to heat and SH-reagents. Detergents were inhibitory in all cases. Extraction of the microsomes with KCl, KSCN, urea or Triton X-100 did not change the ratio of diacylglycerol hydrolysis at pH 4.8 and 8.0. The results of subcellular fractionation studies showed that there was no significant enrichment of the acid lipase in any fraction.


Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1.
Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (glypican). Molecular characterization and phylogenic analysis of 3 immune-related genes (macrophage expressed protein, multicopper oxidase and immunoglobulin domain cell adhesion molecule) were performed. Finally, quantitative PCR revealed significant changes in the expression of immune related genes (multicopper oxidase, macrophage expressed protein, myeloid differentiation factor 88 and interferon-induced protein 44) in oysters experimentally challenged with OsHV-1. These findings provide a first basis for studying the role of innate immunity in response to viruses in bivalves and identified genes may serve as markers of interest in breeding programs in order to obtain selected oysters presenting OsHV-1 resistance.


Psychological distress and risk for eating disorders in subgroups of dieters.
The aim of the present study was to predict the risk of developing an eating disorder in subgroups of dieters, based on the adolescents own accounts of the reason for starting to diet. Eighty-one dieters from a cohort of 595 adolescents (318 boys and 288 girls) aged 15 participated in the present prospective study. Personal interviews at both base-line and follow-up were combined with questionnaire data on depression, social phobia and self-esteem. Four mutually exclusive groups of dieters were identified: vanity dieters, overweight dieters, depressed dieters and feeling fat dieters. Depressed and feeling-fat dieters had a 15-fold risk of having a lifetime eating disorder at age 18 compared to vanity and overweight dieters. Typical teenage vanity dieting and dieting among overweight adolescents appears to be a benign practice, but adolescents dieting because of psychological distress have high-risk of developing an eating disorder.


Ephrin-As play a rhombomere-specific role in trigeminal motor axon projections in the chick embryo.
In this study, we investigate the possible role of ephrin-Eph signaling in trigeminal motor axon projections. We find that EphA receptors are expressed at higher levels by rhombomere 2 (r2) trigeminal motor neurons than by r3 trigeminal motor neurons in the chick embryo. Mapping of rhombomere-specific axon projections shows that r2 and r3 trigeminal motor neurons project to different muscle targets, including the mandibular adductor and the intermandibularis muscles respectively. Ephrin-A5 is expressed in these muscles, especially in some regions of the intermandibularis muscle, and can cause growth cone collapse of both r2 and r3 motor axons in vitro. We demonstrate that in vivo overexpression of ephrin-A5 in the intermandibularis muscle, or overexpression of dominant-negative EphA receptors in trigeminal motor neurons leads to a reduction in branching of r3-derived motor axons specifically. Overexpression of full-length EphA receptors impairs the formation of r3 projections to the intermandibularis muscle. These findings indicate that ephrins and their Eph receptors play a role in trigeminal motor axon topographic mapping and in rhombomere 3-derived projections in particular.


Paeoniflorin inhibits IL‑1β‑induced expression of inflammatory mediators in human osteoarthritic chondrocyte.
Interleukin (IL)-1β serves an important role in the promotion of the growth of osteoarthritis (OA) lesions. Paeoniflorin (PF) has been identified to exert anti‑inflammatory and anti‑arthritic effects. However, it is uncertain whether PF may affect the expression levels of inflammatory mediators in OA chondrocytes. Therefore, the objective of the present study was to determine the effects of PF on the expression levels of inflammatory mediators in IL‑1β‑stimulated human OA chondrocytes. The results of the present study determined that PF inhibited the production of nitric oxide and prostaglandin E2 induced by IL‑1β, and the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in chondrocytes. Additionally, PF significantly inhibited the IL‑1β‑stimulated production of metalloproteinase‑3 (MMP‑3) and MMP‑13 in chondrocytes. PF inhibited the expression of nuclear factor‑κB (NF‑κB), p65 and NF‑κB inhibitor α degradation was induced by IL‑1β in chondrocytes. The results of the present study suggest that PF may inhibit IL‑1β‑induced expression of inflammatory mediators in human OA chondrocytes by suppressing the activation of the NF‑κB signaling pathway. Therefore, PF may be a potential agent in the future treatment of OA.


Incidence and progression of diabetic retinopathy among non-insulin-dependent diabetic subjects: a 4-year follow-up.
To assess the incidence and progression of diabetic retinopathy and explore risk factors associated with them among non-insulin-dependent diabetes mellitus (NIDDM) patients. A total of 471 NIDDM subjects aged > or 40 were recruited from four primary health care centres of northern Taiwan in 1986 and followed up for 4 years. Their ocular fundi were clearly visible by ophthalmoscopy and the status of diabetic retinopathy could be graded. A structured questionnaire interview was conducted to collect basic data. Overnight fasting venous blood was collected every year to measure the levels of glucose, glycosylated haemoglobin (HbA1c), cholesterol and high density lipoprotein cholesterol. Among the 344 subjects who had no retinopathy initially, 66 subjects developed retinopathy 4 years later giving a 4-year cumulative incidence of 19.2%. Of the 120 subjects initially with background or preproliferative retinopathy, evidence of deterioration developed in 36 subjects. The cumulative incidence of progression was 30%. Seven subjects developed proliferative retinopathy giving a cumulative incidence of progression to proliferative retinopathy of 5.8%. The univariate analysis disclosed that the development of retinopathy was correlated with mean fasting blood glucose (MFBG) and HbA1c, diabetic duration, diabetic treatment and residential area. The progression of retinopathy correlated with MFBG and proteinuria, and the progression to proliferative retinopathy correlated with MFBG. Stepwise logistic regression analysis revealed that MFBG and HbA1c were the significant risk factors related to the development of retinopathy. Diabetic control assessed by MFBG or HbA1c was the significant risk factor correlated with the incidence and progression of retinopathy.


Simultanagnosia: when a rose is not red.
Abstract Information regarding object identity ("what") and spatial location ("where/how to") is largely segregated in visual processing. Under most circumstances, however, object identity and location are linked. We report data from a simultanagnosic patient (K.E.) with bilateral posterior parietal infarcts who was unable to "see" more than one object in an array despite relatively preserved object processing and normal preattentive processing. K.E. also demonstrated a finding that has not, to our knowledge, been reported: He was unable to report more than one attribute of a single object. For example, he was unable to name the color of the ink in which words were written despite naming the word correctly. Several experiments demonstrated, however, that perceptual attributes that he was unable to report influenced his performance. We suggest that binding of object identity and location is a limited-capacity operation that is essential for conscious awareness for which the posterior parietal lobe is crucial.


Understanding the shielding effects of whey protein on mulberry anthocyanins: Insights from multispectral and molecular modelling investigations.
Assembling between polyphenols and proteins has been recently spotlighted and this binding is of specific importance in food chemistry since these complexes are typically used in different foodstuffs. A study on the copigmentation among three encapsulation wall-materials, including maltodextrin, gum Arabic, and whey proteins, with mulberry anthocyanins (AC) proved that whey protein (WP) is an outstanding wall-material due to its wrapping and hyperchromicity effects. Additionally, high binding ability of WP with AC was shown to be responsible for its superior copigmentation effects. Accordingly, the underlying shielding mechanism of WP on AC based on their non-covalent assembling was deeply studied using multispectral and computational assays. The fluorometric results demonstrated that a static and heat-stable binding between WP and AC occurred, leading to modification in size, hydrophobicity, and secondary structures of WP. The docking results explained that WP-AC complex was mainly molded via hydrophobic effects of WP surface and subsequently be stabilized by H-bonding and van der Waals forces. These results may contribute to a better understanding on the enhanced colouring proprieties of anthocyanins by using whey proteins.


A simplified method using commercial milk powder for hand-rearing of the Caesarean-derived infant rabbits (author's transl).
An efficient and simplified method for hand-rearing of Caesarean-derived infant rabbits under gnotobiotic condition was devised. The Caesarean-derived infant Dutch or Japanese-White rabbits and their hybrids (F1; Japanese-White female x Dutch male) were reared in sterilized vinyl-isolators by hand-feeding with two kinds of milk diets, A and B, consisted mainly ofa commercial milk powder for dogs and cats (Esbilac) supplemented with several minor components (Table 2) and administered intragastrically once a day through a Nelaton's catheter. Bacteriological examinations revealed that feces and urine were sterile for the first three days. On the third day, Escherichia coli, Staphylococcus epidermidis, Streptococcus faecalis, Bacillus subtilis, Enterococcus, and Bacteroides sp. were given with milk diet and the infant rabbits were reared until 10 to 12 weeks of age. The weaning rate at 5 weeks of age and the raising rate at 3 months of age were approximately 78% and 77%, respectively (Table 3), indicating that feeding once-a-day with a milk diet mainly composed of Esbilac is suitable for the hand-rearing of infant rabbits. There was, however, no significant difference milk diet A and B on the weaning rate.


[Outpatient commitment under court order in psychiatry].
Outpatient commitment under court order is a controversial issue among mental health professionals in different countries. This kind of outpatient involuntary treatment is provided for mental patients suspected to have committed a crime endangering society while in a severe psychotic state. Despite their dangerousness, the Israeli Mental Health Law of 1991 provides outpatient commitment under court order as an alternative to inpatient commitment. This legal provision raises several concerns and important ethical questions. A major dilemma is the question of whether this legal tool is efficacious in stabilizing the mental condition of criminal mental patients in order to prevent the perpetuation of violent crimes in an open setting such as outpatient clinics. Other major concerns are: (a) who bears the responsibility for the implementation of the enforcement? (b) how the enforcement might be implemented? This paper discusses this complex issue and presents some possible solutions aimed at improving the practical use of this important component of the comprehensive modern system of care for mental patients.


Phenylglyoxal modification of the Photosystem II reaction center.
Time-resolved spectroscopic techniques, including optical flash photolysis and electron spin resonance (ESR), have been used in conjunction with fluorescence-induction and dye-reduction assays to monitor electron transport in Photosystem II (PS II) subchloroplast particles incubated with the covalent modifier, phenylglyoxal. Phenylglyoxal-modified digitonin (D-10) particles from spinach are characterized by a high initial fluorescence yield (Fi) and an abolition of the variable component of fluorescence (Fv); an inhibition of PS-II-mediated reduction of dichlorophenol indophenol (DPIP) by sym-diphenylcarbazide; an abolition of flash-induced absorption transients (t1/2 greater than 2 microseconds) at 820 nm attributed to the primary electron donor, P-680+; the inhibition of photoreduction of the acceptor Qa; and the elimination of the ESR Signal 2s and Signal 2f. These observations suggest the critical participation of specific arginine residues on both the oxidizing and reducing sides of Photosystem II and also implicate phenylglyoxal as a quinone-binding site inhibitor (Golbeck, J.H. and Warden, J.T. (1984) Biochim. Biophys. Acta 767, 263-271).


Protective effect of pig brain polypeptides against corticosterone-induced oxidative stress, inflammatory response, and apoptosis in PC12 cells.
Pig brain polypeptides (PBP), active polypeptides hydrolysate extracted from fresh porcine brain tissue, has been shown to have neuroprotective effects in both in vitro and in vivo studies. The present study aimed to explore the molecular mechanisms underlying the neuroprotective effects of PBP in corticosterone (CORT)-induced rat adrenal pheochromocytoma PC12 cells. Cell viability and lactate dehydrogenase (LDH) release were measured in PC12 cells induced with 200 μM CORT in the presence or absence of various concentrations of PBP for 48 h. Intracellular reactive oxygen species (ROS) generation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and glutathione (GSH) content were examined to analyze the effect of PBP on CORT-induced oxidative stress. The levels of pro-inflammatory factors, the percentage of apoptotic cells, and apoptosis-related protein expression in PC12 cells were determined. PBP is mainly composed of protein subunits with molecular weights ranging from 1000 to 10,000 Da. PBP treatment increased cell viability and decreased the release of LDH in CORT-stimulated PC12 cells. Moreover, PBP reduced the level of CORT-induced oxidative stress by decreasing ROS levels and increasing SOD, GSH-Px activities and GSH content. PBP had an inhibitory effect on the CORT-induced inflammatory response through inhibition of the NF-κB signaling pathway. PBP also inhibited CORT-induced apoptosis by downregulating the mitochondrial apoptotic signaling pathway. These results suggest that PBP exerts a neuroprotective effect against CORT-induced cell injury by inhibiting oxidative stress, inflammation, and apoptosis. PBP could act as a neuroprotective agent against nerve injury induced by CORT.


Structure and function of fibrinogen inferred from hereditary dysfibrinogens.
The structure-function relationships of human fibrinogen and their clinical implications are discussed on the basis of data provided by biochemical and electron microscopic analyses of normal and abnormal fibrinogen and by recent crystallographic studies on certain functional domains and segments of normal fibrinogen. Particularly, ultrastructure studies of individual fibrinogen molecules and fibrin networks of structurally elucidated dysfibrinogens enable us to understand the structure-function relationships of these dysfibrinogens more clearly than ever. Electron micrographs of some representative dysfibrinogen molecules are provided.