The interaction between human monocytes and red cells. Specificity for IgG subclasses and IgG fragments.
Studies were carried out in order to characterize the specificity of IgG sub-classes and IgG fragments for rosette formation using red cells and human mononuclear cells. Rosette formation of red cells coated with anti-D was inhibited by free IgG(1) and IgG(3); less inhibition occurred with IgG(2) and IgG(4). Red cells specifically coated with IgG(1) and IgG(3) by chromic chloride were bound to monocytes. Rosette inhibition of anti-D-coated red cells occurred with free Fc fragment of IgG globulin, and only partly with F(ab')(2). Inhibitory capacity of Fc fragments of IgG and gamma(1) heavy chain from heavy chain disease was reversed by the cleavage of disulfide bonds. No inhibition was noted with Fab, or with pepsin components II, III, or IV. These studies indicated that the mononuclear receptor was specific for IgG(1) and IgG(3). The peptide portion of IgG globulin which attached to the mononuclear cell appeared to reside in the N-terminal portion of the Fc fragment and also appeared to require the integrity of the inter-heavy chain disulfide bond. A specific receptor for C3 was not confirmed.


Autoregressive transitional ordinal model to test for treatment effect in neurological trials with complex endpoints.
A number of potential therapeutic approaches for neurological disorders have failed to provide convincing evidence of efficacy, prompting pharmaceutical and health companies to discontinue their involvement in drug development. Limitations in the statistical analysis of complex endpoints have very likely had a negative impact on the translational process. We propose a transitional ordinal model with an autoregressive component to overcome previous limitations in the analysis of Upper Extremity Motor Scores, a relevant endpoint in the field of Spinal Cord Injury. Statistical power and clinical interpretation of estimated treatment effects of the proposed model were compared to routinely employed approaches in a large simulation study of two-arm randomized clinical trials. A revisitation of a key historical trial provides further comparison between the different analysis approaches. The proposed model outperformed all other approaches in virtually all simulation settings, achieving on average 14 % higher statistical power than the respective second-best performing approach (range: -1 %, +34 %). Only the transitional model allows treatment effect estimates to be interpreted as conditional odds ratios, providing clear interpretation and visualization. The proposed model takes into account the complex ordinal nature of the endpoint under investigation and explicitly accounts for relevant prognostic factors such as lesion level and baseline information. Superior statistical power, combined with clear clinical interpretation of estimated treatment effects and widespread availability in commercial software, are strong arguments for clinicians and trial scientists to adopt, and further extend, the proposed approach.


Toward an evolutionary genomics of the avian Mhc.
We review recent developments in the ongoing study of the evolution of the Mhc gene family in birds, with emphasis on class II B genes and results from songbirds obtained in our laboratory. Southern blots suggest a surprising diversity in Mhc class II gene number among various songbird species (Passeriformes). We have sequenced approximately 30 kb contigs from Mhc bearing cosmid clones from two species, red-winged blackbirds (Agelaius phoeniceus) and house finches (Carpodacus mexicanus), whose demography, lifetime reproductive success, epizootics, parasitology and mate choice are among the best studied for natural populations of birds. Of three genes cloned from these species, only one appears strongly polymorphic, and one (from the house finch) is likely a pseudogene. All are similar in structure to those in chickens, albeit with introns intermediate in length between chickens and mammals. Phylogenetic analysis of available class II B peptide-binding region exons suggests that the overwhelming long-term force operating on avian genes sampled thus far has been post-speciation gene duplication and/or concerted evolution. These and other results suggest that the evolution of class II B genes in birds conforms to a mixture of several models of multigene family evolution proposed for the mammalian Mhc, incorporating ongoing homogenization, duplication and pseudogene formation. Large-scale sequencing studies in these and other species, though still in their infancy, will prove invaluable for studying the comparative structures of avian Mhcs, as well as patterns of selection, mutation and linkage disequilibrium at several scales.


Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders.
Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles.


Treatment with nebivolol combined with physical training promotes improvements in the cardiovascular responses of hypertensive rats.
The aim of this study was to determine whether exercise training combined with beta-blocker treatment promotes additional cardiovascular benefits compared with either intervention on its own. For this we used 76 Wistar rats distributed among different groups: normotensive sedentary (NS), normotensive trained (NT), normotensive sedentary treated with beta-blocker (NS_BB), normotensive trained treated with beta-blocker (NT_BB), hypertensive sedentary (HS), hypertensive trained (HT), hypertensive sedentary treated with a beta-blocker (HS_BB), and hypertensive trained rats treated with beta-blocker (HT_BB). Exercise training consisted of 4 weeks of swimming for 60 min a day, 5 days a week. Hypertension was induced with l-NAME (4 weeks), whereas the control rats received saline, and both the control and test rats received nebivolol. The animals underwent surgery to directly record their blood pressure. The HS group showed higher mean arterial pressure (MAP) (P = 0.000), systolic arterial pressure (P = 0.000), and diastolic arterial pressure (P = 0.000) compared with NS. MAP was higher in the HS compared with the HT (P = 0.002), HS_BB (P = 0.018), and HT_BB (P = 0.015) groups. Hearts from the HS group had a higher percentage of collagen compared with the NS and HS_BB groups. The HT_BB and HT groups only had a higher percentage of cardiac collagen by comparison with the HS_BB group. The HT_BB group showed higher levels of macrophages and neutrophils by comparison with the HT and HS_BB groups. Thus, treatment with a beta-blocker combined with physical training was associated with increased cardiovascular benefits over either intervention alone.


The promoter of the endo A cytokeratin gene is activated by a 3' downstream enhancer.
Mouse cytokeratin EndoA is an intermediate filament subunit of the type II cytokeratin class which initiates expression in trophectoderm cells of blastocyst during embryogenesis. To identify the regulatory elements of the endo A gene, we constructed a series of CAT expression vectors and transfected them into PYS-2 cells. We found an enhancer element locating 1 kb downstream from the endo A gene which acts on both the endo A and SV40 promoters. This enhancer consists of six direct repeated sequences with homology to the PEA3 motif in polyoma virus alpha enhancer core. In undifferentiated F9 embryonal carcinoma cells, expression of the construct containing the enhancer was not detected. These results indicate that one of the regulatory mechanisms of endo A gene expression is the 3' downstream enhancer.


Use of Fully Covered Self-expanding Metal Biliary Stents in Pediatrics: A Case Series.
Endoscopic retrograde cholangiopancreatography is used to manage biliary pathology in pediatric patients. Plastic biliary stents have been used in this population for obstructive lesions and bile leaks; however, they are sometimes not effective due to migration, occlusion, or ineffective sealing. Fully covered self-expanding metal stents (FCSEMS) have larger diameters making them more suitable for some situations. Their use in pediatrics has, however, not been defined. The aim of the present study is to describe our experience with FCSEMS at our institution. We present a series of all patients who underwent FCSEMS placement at Children's Hospital Colorado including 3 adolescents and 1 young adult with complex medical needs. Patient age range was 12 to 24 years and the weight ranged between 36 and 75 kg. All patients underwent previous endoscopic retrograde cholangiopancreatography and 1 or more rounds of plastic stenting without adequate clinical response before consideration of FCSEMS placement. Indications included recalcitrant biliary anastomotic stricture after liver transplant, persistent bile leak after needle perforation, recurrent obstructive choledocholithiasis after cholecystectomy, and malignant biliary stricture. Sizes of FCSEMS depended on patient bile duct size and biliary pathology. Dwell time was 6 to 8 weeks. Three patients had resolution of biliary pathology after FCSEMS therapy. One patient had distal migration of FCSEMS necessitating repeat stenting. There were no adverse events from FCSEMS placement or removal. FCSEMS therapy should be considered in appropriate pediatric patients when plastic biliary stents are not effective. Further studies are needed to evaluate the safety and efficacy of FCSEMS in the pediatric age group.


Two new 3-benzylphthalides from Scorzonera veratrifolia Fenzl.
A phytochemical investigation of Scorzonera veratrifolia Fenzl (Asteraceae) yielded two new 3-benzylphthalides, scorzoveratrin (1) and scorzoveratrozit (2), together with five known compounds, chlorogenic acid (3), chlorogenic acid methyl ester (4), cryptochlorogenic acid (5), 4,5-dicaffeoylquinic acid (6) and 3,5-dicaffeoylquinic acid (7). All secondary metabolites were assigned using physicochemical and spectroscopic data. The known compounds 3-7 were isolated for the first time from this species.


Enhancer activation by FGF signalling during otic induction.
Vertebrate ear progenitors are induced by fibroblast growth factor signalling, however the molecular mechanisms leading to the coordinate activation of downstream targets are yet to be discovered. The ear, like other sensory placodes, arises from the pre-placodal region at the border of the neural plate. Using a multiplex NanoString approach, we determined the response of these progenitors to FGF signalling by examining the changes of more than 200 transcripts that define the otic and other placodes, neural crest and neural plate territories. This analysis identifies new direct and indirect FGF targets during otic induction. Investigating changes in histone marks by ChIP-seq reveals that FGF exposure of pre-placodal cells leads to rapid deposition of active chromatin marks H3K27ac near FGF-response genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling otic gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we show that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to selected otic enhancers. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.


A method to evaluate tracer kinetics in small laboratory animals using a series of thermoluminescent dosimeters.
Miniature detector probes have previously been used in large animal models to investigate myocardial 201Tl clearance kinetics. The results of these studies helped develop clinical imaging protocols that greatly improved the accuracy of thallium scintigraphy. However, miniature detector probes are too large to be used in small animals. Thus, if a method could be developed to measure regional time activity curves in small animals, it would provide a cost-effective alternative to both experiments in large animals and/or multiple experiments at varying time points that can produce results only by postmortem analysis of several animals. Accordingly, we developed a method to measure a regional time activity curve of a tracer in rabbits by using a series of thin thermoluminescent dosimeters [CaF2 (dopant) TLDs, 1 mm thick] placed on the surface of the myocardium. Background contributions associated with high blood pool activity are modeled and then subtracted from the initial TLD response. To validate and illustrate this method, thallium kinetics were determined for nonischemic rabbit myocardium (n = 6). Myocardial thallium concentration decreased monoexponentially with a mean half-time equal to 396 +/- 141 min. Arterial blood activity decreased triexponentially with a final half-time of 243 +/- 73 min. No significant difference was found when the myocardial half-time was compared to the final arterial half-time. These findings are consistent with previous work using a cadmium telluride probe in a canine model. Therefore, TLD analysis can provide a cost-effective, reliable, and reproducible method to measure regional myocardial clearance kinetics.


The additional value of anticipated regret and psychopathology in explaining intended condom use among drug users.
Abstract In this study we examine determinants of intended condom use with casual and steady sex partners among drug users. Our aim was to find out whether anticipated regret and psychopathology represent additional factors in explaining condom use behaviour, on top of the constructs defined in traditional psychosocial models of behaviour. A questionnaire measuring intentions, attitude, beliefs, personal norm, subjective norm, descriptive norm, self-efficacy and anticipated regret toward condom use with steady and casual sex partners, and the Symptom Checklist '90 (to measure dimensions of psychopathology) were handed out to 150 Dutch drug users. The results showed that intended condom use with steady sex partners was mainly predicted by self-efficacy, personal norm and anticipated regret (total R2 = 0.41). Lower feelings of hostility and a more positive personal norm, subjective norm and attitude significantly predicted intended condom use with casual sex partners (total R2 = 0.24). The results also showed that intended condom use with steady sex partners seems to result from anticipating possible barriers, whereas condom use with casual sex partners is largely a matter of having safe sex norms. Practical implications of this study for Aids-preventive campaigns are also discussed.


Construction of Discrete Element Constitutive Relationship and Simulation of Fracture Performance of Quasi-Brittle Materials.
In order to solve the problem that the built-in parallel bond model in the discrete element software cannot adequately simulate the post-peak fracture behavior of quasi-brittle materials, a linear cohesive model was established. First, two particles are used to simulate the interface constitutive behavior in different modes. The results show that the new model can better simulate the behavior of Mode-I fracture, Mode-II fracture, and Mixed-mode fracture. Then, the influence of micro-parameters on the newly constructed constitutive model is analyzed, which provides a basis for the determination of micro-parameter values. Finally, the proposed softening model is applied to a three-point bending test of mortar, and the fracture behavior obtained is compared to the acoustic emission results. The simulation results also show that the constitutive model we built can be used to simulate the fracture behavior of quasi-brittle materials such as mortar and concrete.


Modulation of bovine luteal cell synthetic capacity by interferon-gamma.
Previous work from our laboratory has demonstrated that major histocompatibility complex (MHC) antigens are expressed on cultured bovine luteal cells following exposure to the T lymphocyte-derived cytokine, interferon-gamma (IFN-gamma). In light of these actions of IFN-gamma, it was of interest to investigate the effects of this cytokine on other aspects of luteal function. Therefore, bovine luteal cells were cultured for 7 days in the presence or absence of IFN-gamma, and luteal progesterone (P4), prostaglandin F2 alpha (PGF2 alpha), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) production were evaluated. After a 24-h exposure to IFN-gamma (100 U), both PGF2 alpha and 6-keto-PGF1 alpha production were decreased approximately 50% (p less than 0.05). However, as time in culture progressed, IFN-gamma markedly increased the synthesis of both prostaglandins approximately 400% above controls (p less than 0.05). Stimulation of prostaglandin production by IFN-gamma was abrogated by the addition of exogenous P4. During the period of IFN-gamma-stimulated prostaglandin synthesis, LH-stimulated P4 production was inhibited by IFN-gamma treatment. However, the suppression of P4 production by IFN-gamma was not mediated by the increase in prostaglandins since concomitant treatment with indomethacin did not reverse the inhibition of steroidogenesis. These results suggest that IFN-gamma, in addition to an indirect role in promoting immune response mechanisms, may also directly affect luteal function by enhancing luteal prostaglandin synthesis and by inhibiting luteal steroidogenesis.


Diabetes mellitus and periodontal health: dentists' knowledge.
There is a strong body of evidence to support the relationship between periodontal diseases and diabetes mellitus. Unless dental practitioners are aware of this link, they cannot apply the information to their daily practice. The aim of the study was, therefore, to evaluate the knowledge of dental practitioners concerning the effect of diabetes on periodontal health. This was a cross-sectional survey of randomly selected dental practitioners in Kuwait. Participants were asked about specific periodontal complications which they believed that patients diagnosed with diabetes were more susceptible to. A total of 220 dental practitioners (133 general dental practitioners and 87 dental specialists) participated in the study. Less than 60% of all study participants reported that tooth loss due to periodontal reasons and periodontal abscess were frequent among diabetic patients. Dental specialists, especially periodontists, were significantly more aware of periodontal complications associated with diabetes. Factors significantly associated with having knowledge about the effect of diabetes on periodontal health in logistic regression analysis were dentists who were older and those who were specialists. The results of this study indicate that knowledge about the effects of diabetes on periodontal health among this sample of dental practitioners is generally low, and dentists may underestimate the outcomes of periodontal diseases in diabetic patients.


Cannabinoids modulate food preference and consumption in Drosophila melanogaster.
Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of two important sensory regulators Poxn and Orco. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.


Involvement of tubular complexes in pancreatic regeneration after acute necrohemorrhagic pancreatitis.
Localized acute necrohemorrhagic pancreatitis was induced in rats by multiple trypsin injections. Morphological alterations were monitored by light and electron microscopy until complete recovery. In the acute phase, typical pictures of focal acute necrohemorrhagic pancreatitis were observed. In the postacute phase, fibrosis and tubular complexes are characteristic of damaged areas. Tubular complexes appear from the dedifferentiation of acinar cells. They are characterized by duct-like cells bordering wide, empty luminae. In the recovery phase, cellular proliferation was accompanied by differentiation, with progressive acquisition of the morphological characteristics of acinar cells at the periphery of the tubular complexes. In that instance, cellular proliferation was concomitant with the development of collagen septa in tubular complexes. In these structures both duct-like and acinar-like cells presented mitoses. Cell division persisted in the dedifferentiated cells until tubular complexes disappeared. A very similar process was observed in the embryonic pancreas, where organized parenchyma originated from proliferation and differentiation of protodifferentiated cells. We concluded that pancreatic repair following necrohemorrhagic pancreatitis involves proliferation of cells from intact acini and from tubular complexes, at variance with edematous pancreatitis, where regeneration is exclusively due to acinar cell proliferation.


Site-Selective Itaconation of Complex Peptides by Photoredox Catalysis.
Site-selective peptide functionalization provides a straightforward and cost-effective access to diversify peptides for biological studies. Among many existing non-invasive peptide conjugations methodologies, photoredox catalysis has emerged as one of the powerful approaches for site-specific manipulation on native peptides. Herein, we report a highly N-termini-specific method to rapidly access itaconated peptides and their derivatives through a combination of transamination and photoredox conditions. This strategy exploits the facile reactivity of peptidyl-dihydropyridine in the complex peptide settings, complementing existing approaches for bioconjugations with excellent selectivity under mild conditions. Distinct from conventional methods, this method utilizes the highly reactive carbamoyl radical derived from a peptidyl-dihydropyridine. In addition, this itaconated peptide can be further functionalized as a Michael acceptor to access the corresponding peptide-protein conjugate.


Patent Ductus Arteriosus Device Closure in Interrupted Inferior Vena Cava: Challenges Overcome and Lessons Learnt: A Case Series.
Interrupted inferior vena cava (IVC) with azygous continuation provides technical challenge in many percutaneous cardiac interventions. They are performed via the femoral venous access route. We describe four such cases in whom, patent ductus arteriosus (PDA) device closure was done in interrupted IVC. All the four cases were done using the femoral route. Two cases were done via retrograde approach through femoral artery access, in which one was closed with a muscular VSD device and the other with a Gianturco coil. The introduction of newer closure devices helps in the retrograde approach. Two cases were done via anterograde approach through the femoral venous route, with a loop through the azygous vein. One child had transient bradycardia due to cardiac stretch which normalized after the device deployment and introducer system removal. Thus, we describe different femoral approaches in interrupted IVC patients for PDA closure, with the difficulties faced and the complications managed.


Circular RNA UBAP2 facilitates the cisplatin resistance of triple-negative breast cancer via microRNA-300/anti-silencing function 1B histone chaperone/PI3K/AKT/mTOR axis.
Circular RNAs (CircRNAs) have attracted increasing attention in the diagnosis and treatment of human cancers. CircUBAP2 has been identified to promote the progression of triple-negative breast cancer (TNBC), but the function of circUBAP2 in the cisplatin (DDP) resistance of TNBC remains obscure. Our investigation showed that circUBAP2 was significantly upregulated in DDP-resistant TNBC and TNBC sensitivity to DDP could be enhanced by silencing of circUBAP2. Moreover, circUBAP2 was revealed to be a ceRNA for miR-300 to upregulate the expression of anti-silencing function 1B histone chaperone (ASF1B). The effect of circUBAP2/miR-300/ASF1B axis on DDP resistance of TNBC was evaluated by rescue experiments, which demonstrated that circUBAP2 inhibited TNBC sensitivity to DDP through miR-300/ASF1B axis. Furthermore, it was discovered that ASF1B activated PI3K/AKT/mTOR signaling to facilitate the DDP resistance of TNBC cells. In summary, this research revealed a novel regulatory mechanism that circUBAP2 functioned as ceRNA of miR-300 to upregulate ASF1B, which further triggered the PI3K/AKT/mTOR (PAM) signaling to enhance the DDP resistance of TNBC.


Radiological contribution to the diagnosis of early postoperative complications after lung resection for primary tumor: a revisional study.
In the post-operative course of the interventions of lung resection for primary tumor, complications of different nature and severity can arise, recognizing different pathogenetic mechanisms and differing according to the type of resection performed and to the time elapsed after surgery. The low diagnostic accuracy of chest radiography requires a thorough knowledge of the radiologist about all radiographic findings, both normal and pathological, which can be found in the immediate post-operative period (within 30 days after surgery). This article aims to describe the incidence, the clinical features and the radiological aspects of immediate complications following pulmonary resections, with specific reference to those in which the diagnostic imaging provides a fundamental contribution.


Structure and chemical composition of the cell walls from the haploid yeast and mycelial forms of Ustilago maydis.
Isolated or in vivo cell walls from the yeast and mycelial forms of haploid Ustilago maydis were not stained by the normal osmium procedure for electron microscopy. KMnO4 stained mycelial walls, revealing a layered structure with a loose electron-dense layer at the cell surface, but stained only the outer surface layer of yeast walls. Walls were purified from extracts obtained by ballistic and ultrasonic disruption. Chemical analysis showed that composition of yeast and mycelial walls was similar. Yeast walls contained higher amounts of neutral sugars and protein, whereas mycelial walls contained more chitin and phosphate. No chitosan or uronic acids were detected. Higher proportions of xylose and mannose were present in yeast walls, whereas the amounts of glucose and galactose were higher in mycelial walls. Fucose, arabinose, and ribose were detected in yeast walls only. Electrophoretic patterns of proteins extracted with SDS, beta 1, 3-glucanase, or chitinase were similar in walls of both morphologies, although some differential bands were identified. Most antigenic proteins appeared in the covalently bound fraction of the wall. Some were common to both morphologies, but others were stage specific.


Steroid receptor concentrations in endometrial carcinoma: effect on survival in surgically staged patients.
Estrogen and progesterone receptor concentrations were measured in the primary tumors of 137 surgically staged women with clinical stages I and II endometrial carcinoma. For each steroid, increasing receptor concentrations were associated with a decrease in hazard (increase in survival) and the effect was linear for each receptor. When expressed dichotomously, steroid receptor status was also significantly associated with a number of known risk factors, and the significance of the association was influenced by the receptor concentration used as the criterion for receptor positivity. In a multivariate analysis, only progesterone receptor concentration affected survival independently, but the effect disappeared when the analysis was restricted to women with disease confined to the uterus. We conclude that the estrogen and progesterone receptor status of the primary tumor is of limited prognostic significance in endometrial carcinoma unless extrauterine disease is present.


History of facial pain diagnosis.
Premise Facial pain refers to a heterogeneous group of clinically and etiologically different conditions with the common clinical feature of pain in the facial area. Among these conditions, trigeminal neuralgia (TN), persistent idiopathic facial pain, temporomandibular joint pain, and trigeminal autonomic cephalalgias (TAC) are the most well described conditions. Conclusion TN has been known for centuries, and is recognised by its characteristic and almost pathognomonic clinical features. The other facial pain conditions are less well defined, and over the years there has been confusion about their classification.


Repeated visual acuity measurement: establishing the patient's own criterion for change.
We measured visual acuity in 10 young subjects, 10 times each over a period of approximately 3 weeks, using Bailey-Lovie charts. We used a consistent end-point criterion and scored each letter read on the chart. We derived the mean and standard deviation of visual acuity measures for each subject, and for the group. The standard deviation for the group was about 3 times that of the individuals in the group. We calculated the criterion for reduction of visual acuity for the group, as group mean plus 1.96 group standard deviations; use of this criterion would consistently fail to detect patients with clinically significant reductions in visual acuity. We recommend that visual acuity be measured to threshold for every patient. Measuring visual acuity between three and five times provides an estimate of the patient's variability and allows a criterion for reduction of visual acuity to be established for the individual patient. Use of this criterion will enhance the sensitivity of visual acuity measurement as a diagnostic tool.


[Stress-Related Disorders in Rehabilitation].
Due to significant changes in the new ICD-11 classification, stress-related disorders have advanced further into clinical and scientific focus. In contrast to the ICD-10 classification, complex posttraumatic stress disorder as well as prolonged grief have been established as independent diagnoses. Additionally, the diagnostic criteria for adjustment disorder were newly conceptualized and refined. Stress-related disorders have a high relevance for out- and inpatient rehabilitation centers. Posttraumatic stress disorder (PTSD) has a 1-year-prevalence in Germany of 1-2%. Comorbidities such as depression or anxiety disorders are common. PTSD may also result from physical illness and can in turn complicate the course of the disease or even lead to chronification of symptoms. The most effective treatment is a trauma-focused psychotherapy, which usually takes place in an outpatient setting. Psychosomatic inpatient rehabilitation is a valuable resource in the treatment plan of PTSD. The optimal point is mostly following the acute therapy when reintegration to work and social life is the aim. As rehabilitation centers can provide a safe therapeutic setting for patients, allowing them to open up about their trauma, it can pave the way to a trauma focused treatment. Additionally, socio-medical aspects of trauma-related disorders will be touched upon in this overview.


Orthognathic Surgery Has a Significant Effect on Perceived Personality Traits and Emotional Expressions.
The effects of orthognathic surgery go beyond objective cephalometric correction of facial and dental disproportion and malocclusion, respectively. The authors hypothesized that there is tangible improvement following surgery that alters publicly perceived personality traits and emotions. The authors used Amazon.com's Mechanical Turk (MTurk), a crowdsourcing tool, to determine how preoperative and postoperative images of orthognathic surgery patients were perceived on six personality traits and six emotional expressions based on posteroanterior and lateral photographs. Blinded respondents provided demographic information and were randomly assigned to one of two sets of 20 photographs (10 subjects before and after surgery). Data on 20 orthognathic surgery patients were collected from 476 individuals. The majority of participants were female (52.6 percent), 18 to 39 years old (67.9 percent), Caucasian (76.6 percent), had some college or technical training or graduated college (72.7 percent), and had an annual income between $20,000 and $99,999 (74.6 percent). A paired t test analysis found that subjects were perceived significantly more favorably after orthognathic surgery in 12 countenance categories: more dominant, trustworthy, friendly, intelligent, attractive, and happy; and also less threatening, angry, surprised, sad, afraid, and disgusted (p < 0.05). Raters with the highest annual income perceived a greater magnitude of dominance after surgery than those earning less (p < 0.001). There is significant improvement in the countenance of patients after orthognathic surgery, with both perceived personality traits and emotions deemed more favorable. Additional work is needed to better understand the physiologic underpinnings of such findings. Crowdsourcing technology offers a unique opportunity for surgeons to gather data regarding laypeople's perceptions of surgical outcomes in areas such as orthognathic surgery.


HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans.
Hepatitis C virus (HCV) may increase pulmonary hypertension (PH) risk among people living with HIV (PLWH). Prior studies on this topic have been relatively small and examined selected populations. We determine whether HIV/HCV coinfection is associated with higher pulmonary artery systolic pressure (PASP) and prevalent echocardiographic PH. We performed a cross-sectional analysis of 6032 (16% HIV/HCV coinfected) Veterans Aging Cohort Study participants enrolled 4/1/2003-9/30/2012 with echocardiographic PASP measures. We performed multiple linear and logistic regression analyses to determine whether HIV/HCV mono- or co-infection were associated with PASP and PH compared to uninfected individuals. Individuals with HIV/HCV coinfection displayed a higher PASP than uninfected individuals ([Formula: see text]=1.10, 95% CI 0.01, 2.20) but there was no association between HIV/HCV coinfection and prevalent PH. Subset analyses examined HIV and HCV disease severity markers separately and jointly. Among PLWH, HCV coinfection ([Formula: see text]=1.47, 95% CI 0.26, 2.67) and CD4 + cell count ([Formula: see text]= - 0.68, 95% CI - 1.10, - 0.27), but not HIV viral load nor ART regimen, were associated with PASP. Among people with HCV, neither HIV coinfection nor HCV biomarkers were associated with PASP. Among US veterans referred for echocardiography, HIV/HCV coinfection was not associated with a clinically significant elevation in pulmonary pressure. Lower absolute CD4 + T-cell count was inversely associated with PASP which warrants further investigation in prospective studies.


The effect of etching on glass polyalkenoate cements.
The effect of acid etching on the surface appearance and flexural strength of four glass polyalkenoate cements was investigated. Specimens were etched for intervals of 10-60 s, both at the recommended time after mixing and after a 24-h delay. The surface texture was examined microscopically. Further specimens were subjected to a 4-point bend test following etching 1 h and 24 h after mixing. Deterioration of the surface appearance occurred as the etching time was increased beyond 10 s following immediate etching. Etching after 24 h reduced surface damage, but a 10-s etch still gave the most favourable surface appearance without loss of particulate material. Etching beyond 10 s significantly reduces flexural strength.


Neuroprotection, Recovery of Function and Endogenous Neurogenesis in Traumatic Spinal Cord Injury Following Transplantation of Activated Adipose Tissue.
Spinal cord injury (SCI) is a devastating disease, which leads to paralysis and is associated to substantially high costs for the individual and society. At present, no effective therapies are available. Here, the use of mechanically-activated lipoaspirate adipose tissue (MALS) in a murine experimental model of SCI is presented. Our results show that, following acute intraspinal MALS transplantation, there is an engraftment at injury site with the acute powerful inhibition of the posttraumatic inflammatory response, followed by a significant progressive improvement in recovery of function. This is accompanied by spinal cord tissue preservation at the lesion site with the promotion of endogenous neurogenesis as indicated by the significant increase of Nestin-positive cells in perilesional areas. Cells originated from MALS infiltrate profoundly the recipient cord, while the extra-dural fat transplant is gradually impoverished in stromal cells. Altogether, these novel results suggest the potential of MALS application in the promotion of recovery in SCI.


Perceived discrimination during prenatal care, labor, and delivery: an examination of data from the Oregon Pregnancy Risk Assessment Monitoring System, 1998-1999, 2000, and 2001.
Although recent research has examined discrimination in health care, no studies have investigated women's experiences during prenatal or obstetrical care. Analyses of data from the Oregon Pregnancy Risk Assessment Monitoring System showed that 18.53% of mothers reported discrimination by providers during prenatal care, labor, or delivery, most commonly because of age or insurance status. Perceived discrimination was associated with maternal characteristics such as age, marital status, and type of insurance, but not with number of subsequent well-baby visits.


A new species of Colobothea Lepeletier & Audinet-Serville, 1825 (Coleoptera: Cerambycidae: Lamiinae) from Ecuador.
Colobotheini is a tribe of Lamiinae (Cerambycidae) which includes 189 species classified into 12 genera (Monné, 2016). This tribe is characterized by a trapezoidal frons, contiguous antennal tubercles, prothorax without lateral spines, elytra elongate with lateral carina, metatarsomere I elongate and tarsal claws divaricate (Galileo & Martins, 2006). Colobothea Lepeletier & Audinet-Serville, 1825 is the largest genus of Colobotheini, with 119 valid species distributed from Mexico to Southern South America, except Chile and latitudes below 35°S.


Volume and Pressure Delivery During Pediatric High-Frequency Oscillatory Ventilation.
Identify variables independently associated with delivered tidal volume (VT) and measured mean airway pressure during high-frequency oscillatory ventilation across the range of pediatric endotracheal tube sizes. In vitro study. Research laboratory. An in vitro bench model of the intubated pediatric respiratory system during high-frequency oscillatory ventilation was used to obtain delivered VT and mean airway pressure (in the distal lung) for various endotracheal tube sizes. Measurements were taken at different combinations of ventilator set mean airway pressure (Paw), amplitude (ΔP), frequency, and test lung compliance. Multiple regression analysis was used to construct multivariable models predicting delivered VT and mean airway pressure. Variables independently associated with higher delivered VT for all endotracheal tube sizes include higher ΔP (p < 0.001), lower frequency (p < 0.001), and higher test lung compliance (p < 0.001). A multiplicative interaction between frequency and ΔP magnifies the delivered VT when ΔP is high and frequency is low (p < 0.001). Delivered mean airway pressure becomes lower than set Paw as ΔP increases (p < 0.001) and frequency increases (p < 0.05). Ventilator set Paw is the largest determinant of delivered mean airway pressure; however, increasing ΔP resulted in a lower delivered mean airway pressure. For example, in a 4.0 mm ID endotracheal tube, increasing ΔP by 10 cm H2O resulted in an average decrease of delivered mean airway pressure by 4.5%. This is the first study to quantify the interaction between ΔP and frequency in delivered VT and the effect of ΔP and frequency on delivered mean airway pressure. These results demonstrate the need to measure or estimate VT and delivered pressures during high-frequency oscillatory ventilation and may be useful in determining optimal strategies for lung protective ventilation during high-frequency oscillatory ventilation.


Asymmetric functional divergence of duplicate genes in yeast.
Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if asymmetrically diverging duplicate gene pairs show increased robustness to deleterious mutations.


Latency of auditory evoked M100 as a function of tone frequency.
This study investigated post-stimulus latency of the M100 component of auditory evoked fields as a function of tone frequency. A 37-channel biomagnetometer was used to record neuromagnetic fields over the temporal lobe in response to monaurally presented tones. M100 peaks in evoked field amplitude were found for each subject. The post-stimulus latency was observed to vary parabolically with tone frequency. Latencies as short as 99 ms were found in response to mid-audio range frequencies (1000-2000 Hz), whereas lower (100-500 Hz) and higher (3000-5000 Hz) frequencies were associated with longer latencies (up to 153 ms). All fields gave M100 dipole localizations in auditory cortex. Although it was not possible to resolve spatial tonotopy, it appears that frequency information is encoded in the temporal evoked response.


Cigarette smoking intentions and physical fitness: a multivariate study of high school males.
This study was conducted to determine the extent to which several measures of physical fitness, treated compositely and individually, vary among adolescent males differentiated according to cigarette smoking status (i.e., strong intenders, mild intenders, and nonintenders). A total of 381 high school males were administered The Physical Performance Test for California to measure six traits of physical fitness, and a written questionnaire to assess smoking intentions and demographic data. As hypothesized, the teenage males who reported no intentions of smoking cigarettes were significantly more physically fit than were mild intenders and strong intenders, especially the latter. Etiological factors mediating the association are discussed within an underlying theme of prevention and cessation of the habit.


Effects of phosphine ligand chelation on the reactivity of monomeric parent amido ruthenium complexes: synthesis and reactivity of such a complex bearing monodentate ligands.
The parent amido complex cis-(PMe(3))(4)Ru(H)(NH(2)) (2) has been prepared via the deprotonation of [cis-(PMe(3))(4)Ru(H)(NH(3))(+)][BPh(4)(-)]. The amido complex is a somewhat weaker base than the DMPE analogue trans-(DMPE)(2)Ru(H)(NH(2)) but is still basic enough to quantitatively deprotonate fluorene and reversibly deprotonate 1,3-cyclohexadiene and toluene. Complex 2 exhibits very labile phosphine ligands, two of which can be replaced by DMPE to yield the mixed complex cis-(PMe(3))(2)(DMPE)Ru(H)(NH(2)). Because of the ligand lability, 2 also undergoes hydrogenolysis and rapid exchange with labeled NH(3). The amide complex reacts with alkyl halides to yield E2 and S(N)2 products, along with ruthenium hydrido halide complexes including the ruthenium fluoride cis-(PMe(3))(4)Ru(H)(F). Ruthenium hydrido ammonia halide ion pair intermediates [cis-(PMe(3))(4)Ru(H)(NH(3))(+)][X(-)] are observed in some deprotonation and E2 reactions, and measurement of the equilibrium constants for NH(3) displacement from these complexes suggests that they benefit from significant hydrogen bonding between X(-) and NH(3) groups. Cumulenes also react with complex 2 to afford the products of insertion into an NH bond. The rates of neither these NH insertion reactions nor the reversible deprotonation reactions show any dependence on the concentration of PMe(3) present, suggesting that these reactions take place directly at the NH(2) group and do not involve precoordination of substrate to the metal center.


Probiotic administration among free-living older adults: a double blinded, randomized, placebo-controlled clinical trial.
Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults. Thus, therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality. The aim of this double-blinded, randomized, placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults. The study enrolled general older adults (>65 years). After eligibility screening qualified subjects (n = 290) participated in a 2-arm study design, with each arm consisting of 12 weeks of intervention of either active or placebo product. Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing, anxiety and stress. Follow up was performed at 8 and 12 weeks. No persistent significant effects were observed on the primary or secondary outcome parameters of the study. A modest effect was observed in the probiotic arm, were levels of stress decreased at week 8 and 12. Similarly, we found that subjects suffering from indigestion and abdominal pain, respectively, showed a significant decrease of anxiety at week 8 after probiotic treatment, but not at week 12. The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri. Neither was any significant improvement in wellbeing, stress or anxiety observed. Even though the RCT had a negative outcome, the study highlights issues important to take into consideration when designing trials among older adults. Clinicaltrials.gov/ NCT01837940 .


Safety and efficacy of caproamin fides and tranexamic Acid versus placebo in patients undergoing coronary artery revascularization.
Excessive fibrinolysis contributes to post-cardiopulmonary bypass bleeding. Tranexamic Acid (TXA) and Caproamin Fides are synthetic lysine analogues that inhibit plasminogen-fibrin binding. The present study aimed to compare TXA and Caproamin Fides versus placebo in patients undergoing elective coronary artery revascularization. We analyzed perioperative data of 300 adult patients undergoing coronary artery revascularization. Patients were randomly allocated to receive TXA (n=100), Caproamin Fides (n=100) or placebo (n=100) during perioperative time. Mediastinal bleeding during the first 24 hours post-operation, transfusion requirement and post-surgical complications were assessed. Most descriptive and intra-operative parameters were well comparable between the 3 study groups. Except for mean number of packed red blood cell (PRBC) units transfused during ICU stay (P=0.01), patients in the Caproamin Fides and TXA groups did not show any statistically significant differences regarding transfusion of blood products during peri-operative period. There was no evidence of a significant difference in mediastinal blood loss during the first 24 hours post-operation between the patients receiving TXA or placebo, while patients in the Caproamin Fides group had significantly lower mediastinal bleeding than the other 2 groups (Caproamin Fides vs. placebo, P=0.002, <0.001 and <0.001 at 6, 12 and 24 hours post-operation; Caproamin Fides vs. TXA, P=0.009, 0.003, <0.001 at 6, 12 and 24 hours post-operation). The incidence of postoperative complications were comparable between Caproamin Fides and TXA groups (P>0.05). In conclusion, Caproamin Fides seems to be superior to TXA regarding the blood saving effects in patients undergoing coronary artery revascularization.


Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification of Archaea: towards the universal identification of living organisms.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) identification of Archaea has been limited to some environmental extremophiles belonging to distant taxa. We developed a specific protocol for MALDI-TOF-MS identification of Archaea and applied it to seven environmental human-associated Methanobrevibacter smithii, Methanobrevibacter oralis, Methanosphaera stadtmanae, and the recently described Methanomassiliicoccus luminyensi Archaea. After mechanical lyse, we observed a unique protein profile for each organisms comprising 7-24 peaks ranging from 3,015 to 10,632 Da with a high quality score of 7.38 ± 1.26. Profiles were reproducible over successive experiments performed at 1, 2, and 3-week growth durations and unambiguously distinguished the Archaea from all of the 3,995 bacterial spectra in the Brüker database. After the incorporation of the determined profiles into a local database, archaeal isolates were blindly identified within 10 min with an identification score of 1.9-2.3. The MALDI-TOF-MS-based clustering of these archaeal organisms was consistent with their 16S rDNA sequence-based phylogeny. These data prove that MALDI-TOF-MS profiling could be used as a first-line technique for the identification of human Archaea. In complement to previous reports for animal cells, Bacteria and giant viruses, MALDI-TOF-MS therefore appears as a universal method for the identification of living unicellular and multicellular organisms.


Novel synthesis of polymer and carbonaceous nanomaterials via a micelle/silicate nanostructured precursor.
Mesoporous carbonaceous materials with relatively high surface area have been synthesized by a new method composed of in situ polymerization of divinylbenzene in the hydrophobic phase of a hexagonally arrayed micelle/silicate nanocomposite and subsequent carbonization and hydrofluoric acid treatments, while rod-like carbons were obtained from a direct incorporation of divinylbenzene into the mesopores of MCM-41.


Hormone replacement therapy and stroke risk in older women.
Studies of the effect of hormone replacement therapy (HRT) on the risk of stroke in postmenopausal women have yielded divergent results. Many of the studies had small numbers of estrogen-using women and relatively young women. All were confounded because women who use estrogen are healthier than the general population. Case-control studies, which included a larger number of cases, usually were limited to stroke survivors and had problems of recall bias regarding exposure. We describe the independent risk of fatal and nonfatal stroke in a socioeconomically homogeneous cohort of older, postmenopausal, community-dwelling women in Rancho Bernardo, California, who had a high rate of past or current HRT use. During 1984-1987, estrogen use and stroke risk factors were ascertained for 1031 women over age 60 without a history of stroke in the Rancho Bernardo cohort. Stroke deaths were monitored by obtaining 100% of death certificates, and nonfatal strokes were determined through questionnaires. At baseline, the average age was 73.1 years, 27% were current estrogen users, and 45% were past estrogen users. Over 8.8 follow-up years, 263 deaths occurred, and 37 of the death certificates listed stroke as an underlying or contributing cause of death. Only 7 of current HRT users had a stroke compared with 16 former users and 14 never users. The age-adjusted odds ratio (OR) was 0.92 (95% CI = 0.56-1.50) in HRT users versus never users. Results were not materially changed in multiply adjusted analyses. Similar analyses of nonfatal strokes and transient ischemic attacks (n = 20) showed an increased risk (OR = 3.02, 95% CI = 0.70-13.08). This study provides no evidence that HRT prevents stroke in older women, but the confidence intervals are wide, suggesting that more studies are needed.


Vaccines based on whole recombinant Saccharomyces cerevisiae cells.
The ultimate goal of therapeutic vaccines is to activate and exploit the patient's own immune system to vigorously and dynamically seek and eradicate established malignant or virally infected cells. Therapeutic vaccines also offer the potential for preventing disease recurrence. Saccharomyces cerevisiae-based vaccines, where the yeast is engineered to express viral or tumor antigens, represent an ideal therapeutic approach due to their ability to stimulate tumor- or viral-specific CD4(+) and CD8(+) T-cell responses that are capable of reducing disease burden. This review describes preclinical and clinical studies supporting the development of S. cerevisiae-based therapeutic vaccines for the treatment of cancer and viral diseases, as well as multimodal strategies in which therapeutic vaccines are combined with cytotoxic drugs to achieve a greater clinical response.


Novel computerized health risk appraisal may improve longitudinal health and wellness in primary care: a pilot study.
Health Risk Appraisals (HRAs) have been implemented in a variety of settings, however few studies have examined the impact of computerized HRAs systematically in primary care. The study aimed at the development and pilot testing of a novel, comprehensive HRA tool in primary care practices. We designed, implemented and pilot tested a novel, web-based HRA tool in four pair-matched intervention and control primary care practices (N = 200). Outcomes were measured before and 12 months after the intervention using the HRA, patient surveys, and qualitative feedback. Intervention patients received detailed feedback from the HRA and they were encouraged to discuss the HRA report at their next wellness visit in order to develop a personalized wellness plan. Estimated life expectancy and its derivatives, including Real Age and Wellness Score were significantly impacted by the HRA implementation (P<0.001). The overall rate of 10 preventive maneuvers improved by 4.2% in the intervention group vs. control (P = 0.001). The HRA improved the patient-centeredness of care, measured by the CAHPS PCC-10 survey (P = 0.05). HRA use was strongly associated with better self-rated overall health (OR = 4.94; 95% CI, 3.85-6.36) and improved up-to-dateness for preventive services (OR = 1.22; 95% CI, 1.12-1.32). A generalized linear model suggested that increase in Wellness Score was associated with improvements in patient-centeredness of care, up-to-dateness for preventive services and being in the intervention group (all P<0.03). Patients were satisfied with their HRA-experience, found the HRA report relevant and motivating and thought that it increased their health awareness. Clinicians emphasized that the HRA tool helped them and their patients converge on high-impact, evidence-based preventive measures. Despite study limitations, results suggest that a comprehensive, web-based, and goal-directed HRA tool can improve the receipt of preventive services, patient-centeredness of care, behavioral health outcomes, and various wellness indicators in primary care settings.


Silk Fibroin/Polyvinyl Pyrrolidone Interpenetrating Polymer Network Hydrogels.
Silk fibroin hydrogel is an ideal model as biomaterial matrix due to its excellent biocompatibility and used in the field of medical polymer materials. Nevertheless, native fibroin hydrogels show poor transparency and resilience. To settle these drawbacks, an interpenetrating network (IPN) of hydrogels are synthesized with changing ratios of silk fibroin/N-Vinyl-2-pyrrolidonemixtures that crosslink by H₂O₂ and horseradish peroxidase. Interpenetrating polymer network structure can shorten the gel time and the pure fibroin solution gel time for more than a week. This is mainly due to conformation from the random coil to the β-sheet structure changes of fibroin. Moreover, the light transmittance of IPN hydrogel can be as high as more than 97% and maintain a level of 90% within a week. The hydrogel, which mainly consists of random coil, the apertures inside can be up to 200 μm. Elastic modulus increases during the process of gelation. The gel has nearly 95% resilience under the compression of 70% eventually, which is much higher than native fibroin gel. The results suggest that the present IPN hydrogels have excellent mechanical properties and excellent transparency.


Intramedullary spinal cord cavernous malformations.
Although originally the subject of rare case reports, intramedullary spinal cord cavernous malformations (CMs) have recently surfaced in an increasing number of case series and natural history reports in the literature. The authors reviewed 27 publications with 352 patients to consolidate modern epidemiological, natural history, and clinical and surgical data to facilitate decision making when managing these challenging vascular malformations. The mean age at presentation was 42 years without a sex predilection. Thirty-eight percent of the cases were cervical, 57% thoracic, 4% lumbar, and 1% unspecified location. Nine percent of the patients had a family history of CNS CMs. Twenty-seven percent of the patients had an associated cranial CM. On presentation 63% of the patients had motor deficits, 65% had sensory deficits, 27% had pain, and 11% had bowel or bladder dysfunction. Presentation was acute in 30%, recurrent in 16%, and progressive in 54% of cases. An overall annual hemorrhage rate was calculated as 2.5% for 92 patients followed up for a total of 2571 patient-years. Across 24 reviewed surgical series, a 91% complete resection rate was found. Transient morbidity was seen in 36% of cases. Sixty-one percent of patients improved, 27% were unchanged, and 12% were worse at the long-term follow-up. Using this information, the authors review surgical nuances in treating these lesions and propose a management algorithm.


Induction of mRNA for Phosphoenolpyruvate Carboxylase Is Correlated with a Decrease in Shoot Water Content in Well-Irrigated Mesembryanthemum crystallinum.
The abundance of mRNA specific for phosphoenolpyruvate carboxylase (PEPCase) was measured in leaves from well-watered plants of Mesembryanthemum crystallinum. Plants grown side by side in pots of four different volumes (0.16, 0.74, 2.6, 6.5 liters) were compared. The time of increase in the steady-state level of PEPCase mRNA in well-watered plants was dependent on soil volume. The larger the pot, the later PEPCase transcripts were increased. PEPCase mRNA induction started when shoot water content decreased to well below 4000% of dry weight. No positive correlation with the developmental status of the plants could be found. The data indicate that PEPCase mRNA induction in well-watered plants up to 10 weeks of age is controlled environmentally rather than developmentally.


Effect of current density on the microstructure and morphology of the electrodeposited nickel coatings.
The aim of this research work was to study the effect of deposition current density on microstructure and surface morphology of electrodeposited nickel coatings. For this purpose, nickel deposits have been synthesized by direct current from Watts bath without additive, to limit the incorporation of pollutants resulting from surface adsorption or electro-activity of these compounds. Nickel deposits have been investigated by scanning electron microscopy and X-ray diffraction. Cyclic voltammetry was also used to gain information on the general behavior of the deposition. The optimum conditions of deposition were established and the influence of current density on the grain size, surface morphology, and crystal orientation was determined.


FDG-PET in prosthetic graft infections.
Graft infection following prosthetic vascular reconstruction is an uncommon but severe complication. The clinical presentation is often subtle and nonspecific and may occur long after surgery. Although defining a prosthetic vascular graft infection can be difficult, early diagnosis and treatment are essential for the correct choice of treatment to prevent further complications as well as the high morbidity and mortality associated with repeat surgery and removal of infected grafts. False-positive results may lead to unnecessary surgery while failure to diagnose graft infection may have life-threatening sequels. Scarce literature that is currently available regarding the role of (18)F-labeled fluorodeoxyglucose imaging for assessment of vascular graft infection suggests that this modality may represent reliable noninvasive imaging modality in this specific clinical setting. PET/CT increases the test specificity and thus improves diagnostic accuracy. The precise anatomic localization of increased (18)F-labeled fluorodeoxyglucose PET/CT enables accurate differentiation between graft and adjacent soft tissue infection leading to more accurate diagnosis and subsequent optimized therapeutic strategy.


Testosterone acts directly at the pituitary to regulate gonadotropin-releasing hormone-induced calcium signals in male rat gonadotropes.
We have recently shown that castration alters GnRH-induced calcium (Ca2+) signaling in the gonadotropes of male rats. Instead of generating spike-plateau Ca2+ responses to high concentrations of GnRH (100 nM), the majority of gonadotropes from castrated rats have oscillatory Ca2+ responses, which are generally only seen with low concentrations of GnRH in the gonadotropes of intact rats. This change in the nature of GnRH-induced Ca2+ responses is prevented by in vivo testosterone treatment. The aims of the present study were, therefore, to determine if testosterone acts directly at the pituitary or via the regulation of hypothalamic GnRH secretion. Accordingly, castrated male rats were treated with a GnRH antagonist to ablate the effects of increased GnRH secretion at the pituitary gland. GnRH antagonist treatment (10 microg/100 g BW, twice daily for 7 days from the time of castration) decreased the concentration of LH in the serum of castrated rats (0.4 +/- 0.1 ng/ml vs. 11.2 +/- 0.4 ng/ml in untreated castrated rats, mean +/- SEM) but had no effect on the proportion of gonadotropes having oscillatory Ca2+ responses to 100 nM GnRH when compared with untreated castrated rats (63% in antagonist-treated castrated rats vs. 70% in untreated castrated rats). The GnRH antagonist treatment did not, however, interfere with the ability of in vivo testosterone treatment (100 microg/100 g body weight/day) to decrease the proportion of gonadotropes having oscillatory Ca2+ responses to 100 nM GnRH (26% in testosterone-treated rats vs. 25% in testosterone and antagonist-treated rats). These findings indicate that testosterone acts directly at the pituitary, and not by altered GnRH secretion, to modulate GnRH-induced Ca2+ signals. To confirm this suggestion, cultured gonadotropes of castrated male rats were treated in vitro with 10 nM testosterone. Testosterone treatment for twelve, but not 4 h, restored the proportion of gonadotropes having oscillatory Ca2+ responses to that seen in gonadotropes from intact rats. The in vitro effects of testosterone over 12 h were prevented by concomitant treatment with the protein synthesis inhibitor cycloheximide (10 microM), which, when given alone, had no effect on GnRH-induced Ca2+ signals in cells from castrate male rats. Taken together, these findings suggest that testosterone has a direct genomic action at the pituitary to regulate GnRH-induced Ca2+ signals, via a process that involves new protein synthesis.


Endometrial safety: a key hurdle for selective estrogen receptor modulators in development.
Selective estrogen receptor modulators (SERMs) have the ability to provide mixed functional estrogen receptor (ER) agonist or antagonist activity, depending on the target tissue. Tamoxifen, the first SERM available for clinical use, is regarded as a highly effective agent for the prevention and treatment of breast cancer. However, tamoxifen exhibits ER agonist activity in the uterus and is associated with an increased risk of endometrial hyperplasia and malignancy. Endometrial safety has been an important consideration in the clinical development of SERMs, with improved benefit-risk profiles. Raloxifene, which is currently approved for the prevention and treatment of postmenopausal osteoporosis and for the prevention of breast cancer, seems to have neutral effects on the uterus. Promising results have been observed with the targeted development of newer and more tissue-specific SERMs, many of which are under investigation for postmenopausal osteoporosis. Of the newer SERMs in development, lasofoxifene has been shown to reduce fracture risk and decrease the incidence of breast cancer but has been associated with an increased incidence of vaginal bleeding, endometrial thickening, and endometrial polyps. Lasofoxifene and ospemifene have shown beneficial effects on the vaginal epithelium. Phase 3 clinical data have shown that bazedoxifene is effective in preventing and treating postmenopausal osteoporosis, without adverse effects on the endometrium or breast. Arzoxifene has been evaluated in phase 3 trials for postmenopausal osteoporosis and has been studied for the treatment of uterine malignancies but is no longer in clinical development. Further investigation of newer SERMs is warranted to more clearly define the endometrial safety of these agents.


Developmental dyslexia in a regular orthography: can the reading profile be reduced to strategic control?
In languages with regular orthographies, the identification of different forms of reading impairment (such as surface or phonological dyslexia) has proved elusive. Alternatively, it has been proposed that different patterns of errors depend upon strategic choices on the part of the reader. The present study aimed to test this strategic interpretation by evaluating the effectiveness of instructions to read quickly (or accurately) in modifying the reading rate and types of errors of dyslexic children. Further, drawing on an error classification based on the contrast between sounding-out behaviour and word substitution, we examined the types of reading error that best characterize the deficit in a language with regular orthography (Italian). Thirty children with dyslexia and 30 chronologically age-matched controls read aloud passages and word lists with instructions to emphasize either rate or accuracy. When asked to read quickly, children with dyslexia increased their reading rate (although less than skilled children). However, the type of instructions had little influence on reading errors. Therefore, the results did not support the view that strategic control has an important role in modulating the types of reading errors made by children with dyslexia. For word lists, sounding-out behaviour, errors in stress assignment, and form-related nonwords were useful to correctly identifying children with dyslexia. For text passages, sounding-out behaviour and form-related errors were the best predictors of group membership. Thus, specific types of errors are a fundamental component of the reading deficit in children who speak a language with regular orthography over and above their reading slowness.


[Prenatal diagnosis of familial amyloidotic polyneuropathy].
Utilization of the in vitro DNA amplification method for prenatal diagnosis of familial amyloidotic polyneuropathy (FAP) in a German family was reported at the 1st symposium on FAP and other transthyretin related disorders, which was held in Granja, Portugal, in September 1989. Fetal DNA was prepared from chorionic villi and a part of the transthyretin (TTR) gene that may carry the FAP type I mutation was enzymatically amplified. The presence of the mutant TTR gene in fetal DNA was demonstrated by restriction analysis of the amplified DNA. Two other groups also reported prenatal diagnosis of FAP by polymerase chain reaction and restriction analysis.


Phospholipase D as a catalyst: application in phospholipid synthesis, molecular structure and protein engineering.
Phospholipase D (PLD) is a useful enzyme for its transphosphatidylation activity, which enables the enzymatic synthesis of various phospholipids (PLs). Many reports exist on PLD-mediated synthesis of natural and tailor-made PLs with functional head groups, from easily available lecithin or phosphatidylcholine. Early studies on PLD-mediated synthesis mainly employed enzymes of plant origin, which were later supplanted by ones from microorganisms, especially actinomycetes. Many PLDs are members of the PLD superfamily, having one or two copies of a signature sequence, HxKxxxxD or HKD motif, in the primary structures. PLD superfamily members share a common core structure, and thereby, a common catalytic mechanism. The catalysis proceeds via two-step reaction with the formation of phosphatidyl-enzyme intermediate. Both of the two catalytic His residues are critical in the reaction course, where one acts as a nucleophile, while the other functions as a general acid/base. PLD is being engineered to improve its activity and stability, alter head group specificity and further identify catalytically important residues. Since the knowledge on PLD enzymology is constantly expanding, this review focuses on recent advances in the field, regarding PLD-catalyzed synthesis of bioactive PLs, deeper understanding of substrate recognition and binding mechanism, altering substrate specificity, and improving thermostability. We introduced some of our recent results in combination with existing facts to further deepen the story on the nature of this useful enzyme.


Regulation of Renal Differentiation by Trophic Factors.
Classically, trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. However, most neurotrophic factors also have important functions outside of the nervous system. Especially essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs). Here we discuss how trophic factor-induced signaling contributes to the control of ureteric bud (UB) branching morphogenesis and to maintenance and differentiation of nephrogenic mesenchyme in embryonic kidney. The review includes recent advances in trophic factor functions during the guidance of branching morphogenesis and self-renewal versus differentiation decisions, both of which dictate the control of kidney size and nephron number. Creative utilization of current information may help better recapitulate renal differentiation in vitro, but it is obvious that significantly more basic knowledge is needed for development of regeneration-based renal therapies.


Structural determinants in domain II of human glutathione transferase M2-2 govern the characteristic activities with aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine, and 1,2-dichloro-4-nitrobenzene.
Two human Mu class glutathione transferases, hGST M1-1 and hGST M2-2, with high sequence identity (84%) exhibit a 100-fold difference in activities with the substrates aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine (cyanoDMNG), and 1,2-dichloro-4-nitrobenzene (DCNB), hGST M2-2 being more efficient. A sequence alignment with the rat Mu class GST M3-3, an enzyme also showing high activities with aminochrome and DCNB, demonstrated an identical structural cluster of residues 164-168 in the alpha6-helices of rGST M3-3 and hGST M2-2, a motif unique among known sequences of human, rat, and mouse Mu class GSTs. A putative electrostatic network Arg107-Asp161-Arg165-Glu164(-Gln167) was identified based on the published three-dimensional structure of hGST M2-2. Corresponding variant residues of hGSTM1-1 (Leu165, Asp164, and Arg167) as well as the active site residue Ser209 were targeted for point mutations, introducing hGST M2-2 residues to the framework of hGST M1-1, to improve the activities with substrates characteristic of hGST M2-2. In addition, chimeric enzymes composed of hGST M1-1 and hGST M2-2 sequences were analyzed. The activity with 1-chloro-2,4-dinitrobenzene (CDNB) was retained in all mutant enzymes, proving that they were catalytically competent, but none of the point mutations improved the activities with hGST M2-2 characteristic substrates. The chimeric enzymes showed that the structural determinants of these activities reside in domain II and that residue Arg165 in hGST M2-2 appears to be important for the reactions with cyanoDMNG and DCNB. A mutant, which contained all the hGST M2-2 residues of the putative electrostatic network, was still lacking one order of magnitude of the activities with the characteristic substrates of wild-type hGST M2-2. It was concluded that a limited set of point mutations is not sufficient, but that indirect secondary structural affects also contribute to the hGST M2-2 characteristic activities with aminochrome, cyanoDMNG, and DCNB.


Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population.
Unlike most Western populations, MTHFR 677T is a rare allele and a risk factor for a variety of disorders in India. What kind of nutritional (environmental) and/or genetic factors could contribute to the genetic risk is not known. To assess the incidence of hyperhomocysteinemia and its correlation with the polymorphism in homocysteine (Hcy)-pathway genes and associated cofactors in the native populations of eastern India. Healthy population from four eastern states of India. Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine, vitamin B12 and folic acid. Approximately 30% of the population has hyperhomocysteinemia (>15 μmol/lit; hypHcy) with varying frequencies in the four states from where samples were collected (n=1426). Polymorphisms of MTR and CBS do not affect hypHcy. 677T and 1298C alleles of MTHFR and G80 RFC-1 show association with hypHcy. In contrast, RFC-1 80AA is protective even in presence of 677T MTHFR. Addition of each mutant allele has an additive effect on Hcy level. Vitamin B12 (cofactor in methionine synthesis) clearly modulates the genotypic effect on Hcy level. Although frequency of individuals with low folic acid is ≈11, 49% of the population is vitamin B12 deficient (<220 pg/lit) and has a significant negative correlation with Hcy. Individuals with optimum vitamin B12 and folic acid generally have low Hcy, even in risk genotypes. One of the plausible reasons for susceptibility of individuals with MTHFR C677T in the studied population to various disorders is the high frequency of hyperhomocysteinemia and vitamin B12 deficiency in the 'healthy population'. Apparently, supplementation of vitamin B(12) to this health-impoverished community may help lessen the risk of several multifactorial disorders.


Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.
The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.


Biochemical and structural characterizations of thioredoxin reductase selenoproteins of the parasitic filarial nematodes Brugia malayi and Onchocerca volvulus.
Enzymes in the thiol redox systems of microbial pathogens are promising targets for drug development. In this study we characterized the thioredoxin reductase (TrxR) selenoproteins from Brugia malayi and Onchocerca volvulus, filarial nematode parasites and causative agents of lymphatic filariasis and onchocerciasis, respectively. The two filarial enzymes showed similar turnover numbers and affinities for different thioredoxin (Trx) proteins, but with a clear preference for the autologous Trx. Human TrxR1 (hTrxR1) had a high and similar specific activity versus the human and filarial Trxs, suggesting that, in vivo, hTrxR1 could possibly be the reducing agent of parasite Trxs once they are released into the host. Both filarial TrxRs were efficiently inhibited by auranofin and by a recently described inhibitor of human TrxR1 (TRi-1), but not as efficiently by the alternative compound TRi-2. The enzyme from B. malayi was structurally characterized also in complex with NADPH and auranofin, producing the first crystallographic structure of a nematode TrxR. The protein represents an unusual fusion of a mammalian-type TrxR protein architecture with an N-terminal glutaredoxin-like (Grx) domain lacking typical Grx motifs. Unlike thioredoxin glutathione reductases (TGRs) found in platyhelminths and mammals, which are also Grx-TrxR domain fusion proteins, the TrxRs from the filarial nematodes lacked glutathione disulfide reductase and Grx activities. The structural determinations revealed that the Grx domain of TrxR from B. malayi contains a cysteine (C22), conserved in TrxRs from clade IIIc nematodes, that directly interacts with the C-terminal cysteine-selenocysteine motif of the homo-dimeric subunit. Interestingly, despite this finding we found that altering C22 by mutation to serine did not affect enzyme catalysis. Thus, although the function of the Grx domain in these filarial TrxRs remains to be determined, the results obtained provide insights on key properties of this important family of selenoprotein flavoenzymes that are potential drug targets for treatment of filariasis.


Clinical pharmacokinetics of tacrolimus after the first oral administration in renal transplant recipients on triple immunosuppressive therapy.
Monitoring of tacrolimus blood concentration is of utmost importance in the management of renal transplant recipients because of Narrow Therapeutic Index and highly variable pharmacokinetics. The aim of this study was to detect inter-patient pharmacokinetic variability of tacrolimus and to assess the predictability of individual tacrolimus concentrations at various times of the area under the curve (AUC) seeking to find the best sampling time to predict the exposure of tacrolimus in renal transplant recipients with triple therapy. This oral dose tacrolimus pharmacokinetics study was conducted in 18 Serbian renal transplant recipients on triple immunosuppressive therapy, including basiliximab. The first oral dose of tacrolimus (0.05 mg/kg) was given on day 5 post-transplant; blood concentration was measured by microparticle enzyme immunoassay method. Associations between each sampling time-point of concentrations and AUC(12) were evaluated by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple, stepwise regression analyses. The variance in the strength of association between predicted AUC (AUC(p)) and AUC(12) was reflected by linear regression coefficients. AUC(12) showed remarkable inter-individual variations after the first oral dose of tacrolimus. The area of the maximum AUC was four times higher than that of the minimum AUC. C(4) seems to be an indicator of total body exposure to tacrolimus. Alternatively, the concentrations at 1.5, 4 and 8 hr as an abbreviated AUC were as good a predictor as a full pharmacokinetic study. Our results show a significant difference between men and women. A three-point sampling method seemed to be the best abbreviated AUC for a cost-effective tacrolimus monitoring strategy.


Use of the vial equilibration technique for determination of metabolic rate constants for dichloromethane.
Metabolism of methylene chloride, or dichloromethane (DCM), plays a key role in determining the kinetics and carcinogenicity of the halocarbon. The objectives of this study were: to evaluate and optimize the vial equilibration technique, originally described by Sato and Nakajima (1979a), in order to characterize the hepatic metabolism of DCM by Sprague-Dawley rats; to employ different hepatic microsomal preparations to examine buffer effects on DCM metabolism; and to assess the relative importance and metabolic constants of the mixed-function oxidase (MFO) and glutathione (GSH) S-transferase (GST) metabolic pathways. A crude liver homogenate (20% W/V) was prepared from perfused livers of male Sprague-Dawley (S-D) rats (275-325 g). A 30% glycerol buffer was found to significantly inhibit DCM metabolism, while 0.25 M sucrose buffer containing 10 mM EDTA and 1.15% KCl did not. DCM was incubated with the liver 10,000 g supernatant or microsomes and cofactors in sealed headspace vials. Disappearance of DCM, as a measure of the chemical's metabolism, was monitored by headspace gas chromatography. Different trials were conducted to elucidate time-, enzyme-, and substrate-activity relationships. The scaled-up K(m) and Vmax values for the microsomal fraction were quite similar to optimized in vivo values reported by other investigators. In the current study, DCM appeared to be metabolized preferentially by cytochrome P450 IIE1, since substrates (e.g., pyrazole, ethanol, and glycerol) for this isozyme completely inhibited DCM metabolism. Thus, glycerol should not be used as a P450 stabilizer for preparation or storage of microsomes. Phorone pretreatment caused marked hepatic GSH depletion, but had little effect on the overall rate of DCM metabolism. Quantitatively, the GST pathway in the cytosol played a very minor role in DCM metabolism. It was not possible to accurately calculate metabolic constants for this pathway in S-D rats. The vial equilibration technique, as described here, is a relatively simple and reliable method, which should be broadly applicable for measuring the microsomal metabolism of DCM and other VOCs.


Faunal diversity during rainy season in reclaimed sodic land of Uttar Pradesh, India.
Faunal diversity is an indicator of soil amelioration. Estimating the population size or density of an animal species in an area is fundamental to understand its status and demography and to plan for its management and conservation. Considering this, faunal diversity in reclamed sodic land was monitored during rainy season 2000-01 at different locations of district viz., Aligarh, Etah, Fatehpur, Mainpuri and Raebareli in Uttar Pradesh. The Shannon-Weiner species diversity index (H) of different fauna complex of each location was compared with zero years (1995-1996) indexes (before reclamation). Insects diversity index, in reclaimed sodic soil, varied from 3.8178 (Fatehpur: Bariyampur) to 4.623 (Fatehpur: Katoghan), which was 3.028 in zero year at Katoghan in Fatehpur 'H' index of other-arthropods ranged widely from 0.9743 (Etah: Bawali) to 2.0674 (Mainpuri: Pundari). The species diversity index of molluscs registered as high as 1.8637 at Ladhauwa site in Aligarh, which exhibited identical with Saripur site of Raebareli. 'H' index of mammal resulted with the highest (2.19) at Pundari in district Mainpuri. The avifauna and amphibian's indices were recovered maximal at Saripur site of Raebareli and Bariyampur site of Fatehpur respectively. Our result revealed that various fauna enriched with soil reclamation, which is good indicator of restoration of land, primarily due to soil-arthropods and earthworms and its eventual improvement along with succeeding rice-wheat cropping system widespread over there. It clearly shows that soil fauna strongly affects the composition of natural vegetation and we suggest that this knowledge might improve the restoration and conservation of biodiversity.


[Changes of plasma levels of monoamines in normal pregnancy and pregnancy-induced hypertension women and their significance].
To study the changes of plasma levels of monoamines in pregnant women and investigate the relationship between the monoamines and pregnancy induced hypertension (PIH). Using fluorescence spectrophotometry, we determined the contents of plasma monoamines in 130 normal pregnant (NP), 32 normal non-pregnant (NNP), and 58 PIH women. The levels of norepinephrine (NE) in NP from the 2nd trimester to parturiency were more markedly increased than those of the 1st trimester and of NNP (P < 0.05). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were also obviously increased at the 2nd and 3rd trimester respectively (P < 0.05). Compared with NP, the contents of DA in moderate and severe PIH were markedly and very markedly decreased respectively (P < 0.05 and P < 0.01), while the levels of 5-HT in PIH increased significantly (P < 0.05). NE in PIH was also tending to increase. The changes of monoamines may be one of the causes of small artery spasm in PIH.


Theoretical deposition of carcinogenic particle aggregates in the upper respiratory tract.
Numerous particles suspended in the atmosphere are composed of smaller particular components that form aggregates with highly irregular shape. Such aggregates, among which dusts and soot are the most prominent examples, may be taken up into the respiratory tract and, in the worst case, initiate a malignant transformation of lung cells. Particle aggregates were theoretically modelled by using small spheres with equal diameters (1 nm) and arranging them randomly. This procedure resulted in the generation of various aggregate shapes (chain-like, loose, compact), for which essential parameters such as dynamic shape factors, χ, and aerodynamic diameters, dae , were computed. Deposition of aggregates consisting of 10, 50, 100, and 1,000 nano-spheres was simulated for the uppermost parts of the human respiratory system (extrathoracic region and airway generation 0 to 4), thereby distinguishing between sitting and light-work breathing as well as between nasal and oral inhalation. Based upon the modelling results, aggregate deposition in the human respiratory system can be described as a function of (I) aerodynamic diameter; (II) inhaled particle position within the airway system; and (III) breathing conditions. Therefore, highest deposition values were obtained for nano-scale aggregates (<10 nm), whereas larger aggregates exhibited slightly to significantly reduced deposition probabilities. Extrathoracic regions and uppermost bronchi (generations 0 to 1) were marked by most effective particle capture. Any increase of inhaled air volumes and reduction of breathing times resulted in an enhancement of deposition probabilities of larger particles. Based on the results derived from this study it may be concluded that small particle aggregates are accumulated in the uppermost compartments of the human respiratory tract, where they may unfold their unwholesome potential. In the case of carcinogenic particles being stored in epithelial cells for a longer time span, malignant transformations starting with the formation of cancerous cells and ending with the growth of a tumour have to be assumed.


The endogenous Bacillus subtilis (natto) plasmids pTA1015 and pTA1040 contain signal peptidase-encoding genes: identification of a new structural module on cryptic plasmids.
Various strains of Bacillus subtilis (natto) contain small cryptic plasmids that replicate via the rolling-circle mechanism. Like plasmids from other Gram-positive bacteria, these plasmids are composed of several distinct structural modules. A new structural module was identified on the B. subtilis plasmids pTA1015 and pTA1040. It is composed of two genes: one specifies an unidentified protein with a putative signal peptide; and the other (sipP) specifies a functional type 1 signal peptidase (SPase). The homologous, but non-identical, sipP genes of the two plasmids are the first identified plasmid-specific SPase-encoding genes. With respect to structure and activity, the corresponding enzymes (denoted SipP) are highly similar to the chromosomally encoded SPase, SipP, of B. subtillis and several newly identified SPases of other bacilli. Our findings suggest that plasmid-encoded SPases have evolved because, of under certain conditions, SPase can be a limiting factor for protein secretion in B. subtilis.


A computational method for large-scale identification of esophageal cancer-related genes.
The incidence of esophageal cancer has obvious genetic susceptibility. Identifying esophageal cancer-related genes plays a huge role in the prevention and treatment of esophageal cancer. Through various sequencing methods, researchers have found only a small number of genes associated with esophageal cancer. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. This method fuses graph convolutional network and logical matrix factorization to effectively identify esophageal cancer-related genes through the association between genes. We call this method GCNLMF which achieved AUC as 0.927 and AUPR as 0.86. Compared with other five methods, GCNLMF performed best. We conducted a case study of the top three predicted genes. Although the association of these three genes with esophageal cancer has not been reported in the database, studies by other reseachers have shown that these three genes are significantly associated with esophageal cancer, which illustrates the accuracy of the prediction results of GCNLMF.


Economic evaluation and health care. What does it mean?
Ever since the concept of value for money in health care was introduced into the NHS, economic terms and jargon have become part of our everyday lives--but do we understand what the different types of economic evaluation all mean, particularly those that sound similar to the uninitiated? This article introduces readers to the purpose of economic evaluation, and briefly explains the differences between cost-minimisation analysis (used when the outcomes of the procedures being compared are the same); cost-effectiveness analysis (used when the outcomes may vary, but can be expressed in common natural units, such as mm Hg for treatments of hypertension); cost-utility analysis (used when outcomes do vary--for example, quality of life scales); and cost-benefit analysis (used when a monetary value is being placed on services received). Further articles will deal with each one in more detail.


Deliberations and evaluations of the approaches, endpoints and paradigms for manganese and molybdenum dietary recommendations.
The background of the current dietary recommendations for manganese and molybdenum are described. This article reviews how the previous and current estimated safe and adequate daily dietary intakes (ESADDI) were set, shortcomings in the methods used, concerns about the current recommendations, and brief summaries of new research reports. New approaches, endpoints and paradigms to use for the development of useful recommendations are given.


Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro.
Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection.


The effect of pressure-controlled ventilation on pulmonary mechanics in the prone position during posterior lumbar spine surgery: a comparison with volume-controlled ventilation.
When an anesthetized patient is turned to the prone position using the Wilson frame, dynamic compliance (Cdyn) decreases and peak airway pressure (Ppeak) increases. As pressure-controlled ventilation (PCV) decreases the Ppeak, this prospective, randomized study was designed to compare the effect of PCV and volume-controlled ventilation (VCV) on lung mechanics in the prone position using the Wilson frame during posterior lumbar spine surgery. Forty patients scheduled for posterior lumbar spine surgery were randomly allocated to receive mechanical ventilation using either the VCV (n=20) or PCV (n=20) mode. Respiratory variables (including Ppeak and Cdyn) and oxygenation parameters were recorded at the supine position (Tsupine) and 30 minutes after prone positioning (Tprone). During the study period, tidal volume, minute volume, end-tidal carbon dioxide tension, and positive end-expiratory pressure were comparable between the 2 groups. The Ppeak in the PCV group was lower than that in the VCV group throughout the study period (P=0.007 and 0.003 at Tsupine and Tprone, respectively) and was increased at Tprone compared with Tsupine in both groups. Cdyn was decreased from Tsupine to Tprone in both groups. However, the Cdyn in the PCV group was higher than that in the VCV group during the study period. The arterial oxygen tension was comparable between the 2 groups during the study period. PCV provides lower Ppeak compared with VCV when the ventilator is set to deliver the same tidal volume and variable respiratory rate to maintain a constant end-tidal carbon dioxide tension in patients undergoing posterior lumbar spine surgery in the prone position using the Wilson frame.