Angiotensin II type-I receptor blocker, candesartan, improves brachial-ankle pulse wave velocity independent of its blood pressure lowering effects in type 2 diabetes patients.
Hypertension in diabetic patients has been shown to accelerate the progression of atherosclerosis and angiotensin II type-I (AT1) receptor blocker (ARB) has been shown to have anti-atherosclerosis action independent of its action on blood pressure. Type 2 diabetic patients with hypertension received either ARB (candesartan), or a calcium channel blocker (CCB; amlodipine or nifedipine) for 12 weeks. Though clinical parameters such as blood glucose, HbA1c, and systolic and diastolic pressure were not significantly changed between the two groups, brachial-ankle pulse wave velocity (baPWV) was significantly reduced in the candesartan group when compared to CCB groups. Moreover, candesartan treatment exhibited a tendency of reduction in inflammation markers such as high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6). We conclude that candesartan may improve vascular inflammation independent of its effect on hypertension in diabetes, thus suggesting its efficacy in diabetic patients.


Synthesis and characterization of polyphosphazene microspheres incorporating demineralized bone matrix scaffolds controlled release of growth factor for chondrogenesis applications.
As a promising strategy for the successful regeneration of articular cartilage, tissue engineering has received increasing recognition of control release. Two kinds of functional poly (alanine ethyl ester-co-glycine ethyl ester) phosphazene microspheres with different ratios of side-substituent groups were synthesized by emulsion technique. The rate of degradation/hydrolysis of the polymers was carefully tuned to suit the desired application for control release. For controlled delivery of growth factors, the microspheres overcame most of severe side effects linked to demineralized bone matrix (DBM) scaffolds, which had been previously optimized for cartilage regeneration. The application of scaffolds in chondrogenic differentiation was investigated by subcutaneous implantation in nude mice. In the present study, we have provided a novel microsphere-incorporating demineralized bone matrix (MS/DBM) scaffolds to release transforming growth factor-β1 or insulin-like growth factors-1. Laser confocal fluorescence staining showed that the surface of microspheres was a suitable environment for cell attachment. Histological and immunohistochemical evaluations have shown that significantly more cartilaginous extracellular matrix was detected in MS/DBM group when compared with DBM alone group (P<0.05). In addition, the biomechanical test showed that this composite scaffold exhibited favorable mechanical strength as a delivery platform. In conclusion, we demonstrated that MS/DBM scaffolds was sufficient to support stem bone marrow-derived mesenchymal stem cells chondrogenesis and neo-cartilage formation.


[Sociodemographic features of suicide attempts].
Suicide accounts for about 10% of deaths among psychiatric patients, and life-threatening attempts are much more common than fatalities. Despite progress in defining risk rates and predictive factors, knowledge on which to base sound clinical and public policies regarding suicide prevention and treatment remains remarkably limited. Social risk factors and psychiatry diagnoses are the main arguments to management the suicidal behaviour in emergency room. Female gender is associate with suicide attempts while male gander is associate with completed suicide. Risk of suicide is increased in young and elderly people. Age is a confounding factor in the relationship among suicide and widow, income and professional status. Emigration and anomie are related with suicide. Social factor, as a marker of suicidal behaviour, are a promising research question.


Neural Basis of Somatosensory Spatial and Temporal Discrimination in Humans: The Role of Sensory Detection.
While detecting somatic stimuli from the external environment, an accurate determination of their spatial and temporal properties is essential for human behavior. Whether and how detection relates to human capacity for somatosensory spatial discrimination (SD) and temporal discrimination (TD) remains unclear. Here, participants underwent functional magnetic resonance imaging scanning when simply detecting vibrotactile stimuli of the leg, judging their location (SD), or deciding their number in time (TD). By conceptualizing tactile discrimination as consisting of detection and determination processes, we found that tactile detection elicited activation specifically involved in SD within the right inferior and superior parietal lobules, 2 regions previously implicated in the control of spatial attention. These 2 regions remained activated in the determination process, during which functional connectivity between these 2 regions predicted individual SD ability. In contrast, tactile detection produced little activation specifically related to TD. Participants' TD ability was implemented in brain regions implicated in coding temporal structures of somatic stimuli (primary somatosensory cortex) and time estimation (anterior cingulate, pre-supplementary motor area, and putamen). Together, our findings indicate a close link between somatosensory detection and SD (but not TD) at the neural level, which aids in explaining why we can promptly respond toward detected somatic stimuli.


Chaotic scattering in deformed optical microlasing cavities.
We consider a common class of dielectric optical microlasing cavities with quadrupolar deformations and address the question of the maximally allowed amount of deformation for both high-Q operation and a high degree of directionality of light emission. Our approach is to compute the probability for light rays to be trapped in the cavity by examining chaotic scattering dynamics in the classical phase space. We develop a dynamical criterion for high-Q operation and introduce a measure to quantify the directionality of the light emission. Our results suggest that high-Q and directionality can be achieved simultaneously in a wide range of the deformation parameter.


The law of perceptual stability: well-definedness and validity.
Axiomatic foundations for a theory of perception have been given in a prior communication [Shiman, L. G. (1978) Proc. Natl. Acad. Sci. USA 75, 2049-2053]. The theory is based on mathematically characterized stable images. Stable images model subjective (psychological) states of observers. We showed there is a universal procedure by which such stable images can be assigned to objects of perception (icons), employing observer-dependent perceptual judgements. We construct an abstract model for an icon from the mathematical structure of a stable image that has been assigned to it. We identify the model with the icon. By identifying the model with the object of perception, we can analyze perception of the icon in terms of the mathematical properties of its associated stable images. Thus subjective phenomena, in this mathematical form, can be used to analyze the mechanisms of sensory processes. Grounds for validity of the stability law are given. The procedures are demonstrably universal. A stable image, although subjectively derived from an icon, is a mathematical entity, and has therefore objective status. Stable images give a natural and potentially complete (mathematical) classification of icons, along nontraditional lines, which includes a classification and account of many well-known "visual illusions."Extension of this (static) theory to include time-dependent (kinetic) cases is outlined. We consider grammar for vision, semantics, and the role of stability theory in constructing a unified theory of vision and natural languages.


Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate.
Metazoan evolution involves increasing protein domain complexity, but how this relates to control of biological decisions remains uncertain. The Ras guanine nucleotide exchange factor (RasGEF) Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway during mammalian development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage. We show that the ability of Sos1/Grb2 to appropriately regulate pluripotency and differentiation factors and to initiate PrE development requires collective binding of multiple Sos1/Grb2 domains to their protein and phospholipid ligands. This provides a cooperative system that only allows lineage commitment when all ligand-binding domains are occupied. Furthermore, our results indicate that the interaction domains of Sos1 and Grb2 have evolved so as to bind ligands not with maximal strength but with specificities and affinities that maintain cooperativity. This optimized system ensures that PrE lineage commitment occurs in a timely and selective manner during embryogenesis.


Perturbed replication induced genome wide or at common fragile sites is differently managed in the absence of WRN.
The Werner syndrome protein (WRN) is a member of the RecQ helicase family. Loss of WRN results in a human disease, the Werner syndrome (WS), characterized by high genomic instability, elevated cancer risk and premature aging. WRN is crucial for the recovery of stalled replication forks and possesses both helicase and exonuclease enzymatic activities of uncertain biological significance. Previous work revealed that WRN promotes formation of MUS81-dependent double strand breaks (DSBs) at HU-induced stalled forks, allowing replication restart at the expense of chromosome stability. Here, using cells expressing the helicase- or exonuclease-dead WRN mutant, we show that both activities of WRN are required to prevent MUS81-dependent breakage after HU-induced replication arrest. Moreover, we provide evidence that, in WS cells, DSBs generated by MUS81 do not require RAD51 activity for their formation. Surprisingly, when replication is specifically perturbed at common fragile sites (CFS) by aphidicolin, WRN limits accumulation of ssDNA gaps and no MUS81-dependent DSBs are detected. However, in both cases, RAD51 is essential to ensure viability of WS cells, although by different mechanisms. Thus, the role of WRN in response to perturbation of replication along CFS is functionally distinct from that carried out at stalled forks genome wide. Our results contribute to unveil two different mechanisms used by the cell to overcome the absence of WRN.


Classical versus quantum structure of the scattering probability matrix: chaotic waveguides.
The purely classical counterpart of the scattering probability matrix (SPM)/S(n,m)/(2) of the quantum scattering matrix S is defined for two-dimensional quantum waveguides for an arbitrary number of propagating modes M. We compare the quantum and classical structures of /S(n,m)/(2) for a waveguide with generic Hamiltonian chaos. It is shown that even for a moderate number of channels, knowledge of the classical structure of the SPM allows us to predict the global structure of the quantum one and, hence, understand important quantum transport properties of waveguides in terms of purely classical dynamics. It is also shown that the SPM, being an intensity measure, can give additional dynamical information to that obtained by the Poincaré maps.


Short-form Ron receptor is required for normal IFN-gamma production in concanavalin A-induced acute liver injury.
Abrogation of Ron receptor tyrosine kinase function results in defects in macrophage activation and dysregulated acute inflammatory responses in vivo. Several naturally occurring constitutively active alternative forms of Ron have been identified, including from primary human tumors and tumor cell lines. One of these alternative forms, short-form (SF) Ron, is generated from an alternative start site in intron 10 of the Ron gene that eliminates most of the extracellular portion of the receptor and is overexpressed in several human cancers. To test the physiological significance of SF-Ron in vivo, mice were generated that solely express the full-length form of Ron (FL-Ron). Our results show that elimination of the capacity to express SF-Ron in vivo leads to augmented production of IFN-gamma from splenocytes following stimulation ex vivo with either concanavalin A or anti-CD3/T cell receptor monoclonal antibody. Moreover, in a concanavalin A-induced murine model of acute liver injury, FL-Ron mice have increased production of serum INF-gamma and serum alanine aminotransferase levels and worsened liver histology and overall survival compared with wild-type control mice. Taken together, these results suggest for the first time that SF-Ron impacts the progression of inflammatory immune responses in vivo and further support a role for the Ron receptor and its various forms in liver pathophysiology.


What are the costs to physicians of administrative complexity in their interactions with payers?
(1) Primary care physicians spent significantly more time on administrative tasks than did medical specialists or surgical specialists. (2) All staff in physician practices with one or two physicians spent more time on administrative tasks than did physicians and staff in practices with more than 10 physicians. (3) More than 75 percent of physicians and administrators reported that the administrative burden of interacting with a health plan increased significantly or increased slightly in the past two years. (4) On average, physician practices spent $68,274 per physician per year interacting with health plans. When this average is multiplied by the number of physicians practicing in the United States, the total cost of physicians' interactions with health plans is $31.0 billion.


Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research.
Over the time period from 2006 to 2017, consecutive patients operated on at the University Medical Center Rostock participated in the comprehensive biobanking and tumor-modelling approach known as the HROC collection. Samples were collected using strict standard operating procedures including blood (serum and lymphocytes), tumor tissue (vital and snap frozen), and adjacent normal epithelium. Patient and tumor data including classification, molecular type, clinical outcome, and results of the model establishment are the essential pillars. Overall, 149 patient-derived xenografts with 34 primary and 35 secondary cell lines were successfully established and encompass all colorectal carcinoma anatomic sites, grading and staging types, and molecular classes. The HROC collection represents one of the largest model assortments from consecutive clinical colorectal carcinoma (CRC) cases worldwide. Statistical analysis identified a variety of clinicopathological and molecular factors associated with model success in univariate analysis. Several of them not identified before include localization, mutational status of K-Ras and B-Raf, MSI-status, and grading and staging parameters. In a multivariate analysis model, success solely correlated positively with the nodal status N1 and mutations in the genes K-Ras and B-Raf. These results imply that generating CRC tumor models on the individual patient level is worth considering especially for advanced tumor cases with a dismal prognosis.


The evolving role of community pharmacists during COVID-19 in the UAE; assessing preparedness and knowledge.
To investigate community pharmacists' knowledge about COVID-19 and their preparedness for the pandemic. This cross-sectional online survey was conducted (in community pharmacies in the United Arab Emirates) over 3 weeks (24 May 2020 to 14 June 2020). A proportionate random sample of 491 participants was invited to take part. The SPSS version 26 was used for data management and analysis. The majority of participants (n = 400) had good knowledge about COVID-19 and high level of preparedness for the pandemic control. Most pharmacists agreed (212, 53.0%) or strongly agreed (91, 22.8%) that they have a major role in the management of the ongoing crisis. Most participants had good awareness about the most common methods of COVID-19 transmission (359, 89.7%) and symptoms encountered (368, 92.0%). However, approximately a quarter of participants (103, 25.7%) incorrectly thought COVID-19 was caused by a DNA virus. Participants who had 5-10 and >10 years of experience were 3.95 (P = 0.03) and 1.59 (P = 0.01) times, respectively, were more likely to have good knowledge compared to participants with less than 2 years of experience. Those with good knowledge were more likely to have a specific area for customers with suspected COVID-19 symptoms compared to those with poor knowledge (P = 0.031). This study indicates that years of experience and good knowledge on COVID-19 were significant determinants of pharmacists' preparedness for the pandemic control.


The Use of a Software-Assisted Method to Estimate Fetal Weight at and Near Term Using Magnetic Resonance Imaging.
The aim of this study was to apply a semi-automated calculation method of fetal body volume and, thus, of magnetic resonance-estimated fetal weight (MR-EFW) prior to planned delivery and to evaluate whether the technique of measurement could be simplified while remaining accurate. MR-EFW was calculated using a semi-automated method at 38.6 weeks of gestation in 36 patients and compared to the picture archiving and communication system (PACS). Per patient, 8 sequences were acquired with a slice thickness of 4-8 mm and an intersection gap of 0, 4, 8, 12, 16, or 20 mm. The median absolute relative errors for MR-EFW and the time of planimetric measurements were calculated for all 8 sequences and for each method (assisted vs. PACS), and the difference between the methods was calculated. The median delivery weight was 3,280 g. The overall median relative error for all 288 MR-EFW calculations was 2.4% using the semi-automated method and 2.2% for the PACS method. Measurements did not differ between the 8 sequences using the assisted method (p = 0.313) or the PACS (p = 0.118), while the time of planimetric measurement decreased significantly with a larger gap (p < 0.001) and in the assisted method compared to the PACS method (p < 0.01). Our simplified MR-EFW measurement showed a dramatic decrease in time of planimetric measurement without a decrease in the accuracy of weight estimates.


[A good medical curriculum takes the religious beliefs and cultural background of the students into consideration].
The ethnic composition of the student population is highly diverse, just like that of the Dutch population, and the medical curriculum should take this into consideration. The curriculum assumes that doctors will be able to recognise problems that are related to a particular cultural background. The flexibility that medical curricula are expected to display in the way they deal with cultural diversity may also be expected of both Dutch and originally non-Dutch students. Opening up dilemmas for discussion and searching for solutions in a constructive manner during the medical curriculum can contribute to a professional approach to patients later in life.


Sagittal alignment comparison of Bryan disc arthroplasty with ProDisc-C arthroplasty: a prospective, randomized controlled clinical trial.
A prospective, randomized study of the radiographic outcomes in patients undergoing single-level cervical arthroplasty with Bryan disc and ProDisc-C prosthesis. The purpose of this trial was to compare the alignment changes of Bryan disc arthroplasty (modified techniques) with ProDisc-C arthroplasty. Aggravation of kyphosis is the known challenge after Bryan disc arthroplasty. Both Bryan disc arthroplasty with modified techniques and ProDisc-C arthroplasty were reported to avoid the postoperative local kyphosis. There have been no studies comparing the alignment changes after Bryan disc arthroplasty with ProDisc-C arthroplasty. We conducted a randomized controlled clinical trial enrolling patients with cervical disc disease. Ultimately 20 patients received Bryan disc arthroplasty with modified surgical techniques and 26 patients received ProDisc-C arthroplasty. Functional spinal unit (FSU) and overall cervical alignment (Cobb angle of C2/7) were compared at final follow-up. (1) FSU angle: the FSU angle was maintained for the Bryan disc group (from 0.8 to 0.6 degrees) without statistical significance; the FSU angle increased 2.9 degrees for the ProDisc-C group (from -0.3 to 2.6 degrees) with statistical significance. (2) Overall alignment: the overall alignments did not change for both Bryan disc and ProDisc-C groups. Bryan disc arthroplasty with modified techniques can maintain the lordosis of FSU, whereas ProDisc-C arthroplasty can restore the lordosis of FSU. For the patients with preoperative FSU kyphosis, ProDisc-C arthroplasty may be a better choice to restore the lordosis.


Virus-like particles as particulate vaccines.
Particulate structures hold great promise for the development of effective and affordable recombinant prophylactic as well as therapeutic vaccines. Different types of particulate structures, including virus-like particles (VLPs) and virosomes, have been developed depending on the nature of the viral pathogen to be targeted and the type of immune response (humoral vs cellular) to be elicited. Particulate structures allow the insertion or fusion of foreign antigenic sequences, resulting in chimeric particles delivering foreign antigens on their surface. Similarly, they are used as carriers for foreign antigens, including non-protein antigens, via chemical conjugation. Particulate structures, indeed, represent a very efficient system for delivering antigens to antigen presenting cells (APC) which, in turn, trigger and amplify the adaptive immune response. The present review will address the biological and immunological properties of particulate structures, in particular VLPs, as platform for vaccine development.


Comparison of short- and long-term treatment protocols and the results of second-line quadruple therapy in children with Helicobacter pylori infection.
Research regarding the optimal therapeutic approach to Helicobacter pylori infection in children is ongoing. There is no consensus as to duration of treatment or second-line therapy. The purpose of this study was compare the efficacy of 7-day and 14-day triple therapies and report the results of second-line quadruple therapy in children. A total of 275 consecutive H. pylori-infected patients were enrolled into two groups. Group 1 (n = 180) received triple therapy with 14 days of amoxicillin and clarithromycin and 21 days of proton pump inhibitor. Group 2 (n = 95) received triple therapy including 7 days of amoxicillin and clarithromycin with 21 days of proton pump inhibitor. Subsequently, 89 patients not responding to the triple therapies received quadruple therapy comprising omeprazole (14 days), bismuth subcitrate (7 days), doxycycline (7 days), and metronidazole (7 days). Eradication was evaluated by 13C-urea breath test. The per-protocol eradication rates in groups 1 and 2 were 60.5% and 55.8%, respectively (P = 0.44). In the second interview with 227 patients, severe symptoms were reported to have disappeared in 59% and decreased notably in 34.8%. Helicobacter pylori was eradicated in 66.7% of patients at the end of the quadruple therapy. In the third interview with 75 patients, severe symptoms had decreased in 38.6% and disappeared in 56%. The different duration of the two treatment regimens had no impact on eradication rates. Furthermore, quadruple therapy was necessary to achieve H. pylori eradication after triple therapy. However, the eradication rate with quadruple therapy was still insufficient. Consequently, a new therapeutic approach to H. pylori infection in children is needed.


Atorvastatin in the management of tinnitus with hyperlipidemias.
To determine the role of atorvastatin in management of tinnitus in patients with hyperlipidemia. Quasi-experimental study. ENT Department, Combined Military Hospital, Rawalpindi, from July 2011 to August 2012. Ninety eight patients of tinnitus with sensorineural hearing loss having hyperlipidemia were included in the study. Their pre-therapy serum cholesterols were measured, and tinnitus scores were recorded on a 'Tinnitus handicap questionnaire'. They were administered tablet atorvastatin 40 mg once daily with low fat diet for 8 months. After 8 months of therapy, patients were purposefully divided into responsive and unresponsive group depending on serum cholesterol levels. Post therapy serum cholesterol levels and tinnitus scores were also recorded after 8 months and compared with pre-therapy records. Serum cholesterol came to within normal limits in 51 (52%) patients (responsive group), while it remained high in 47 (48%) patients (unresponsive group). Improvement in tinnitus score in the responsive group was seen in 36 (70.5%) patients and in 2 (4.2%) patients of the unresponsive group. Improvement in tinnitus scores was compared in the two groups using Fisher's exact test and were found to be statistically better in the responsive group (p < 0.001). Tinnitus, in patients having hyperlipidemia, can be successfully dealt with by treating hyperlipidemia with lipid lowering agent atorvastatin.


The C282Y mutation in the haemochromatosis gene (HFE) and hepatitis C virus infection are independent cofactors for porphyria cutanea tarda in Australian patients.
Whether mutations in the putative haemochromatosis gene (HFE) and hepatitis C virus act independently to precipitate porphyria cutanea tarda is unknown. The aim of the study was to investigate the relationship between mutations in HFE, hepatitis C and porphyria cutanea tarda. The frequencies of the C282Y and H63D mutations in HFE were determined in 27 patients with porphyria cutanea tarda and compared with the reported control frequencies. In addition, the presence of hepatitis C virus infection was identified and related to the patients' HFE status. The C282Y mutation was found in 44.4% of patients compared with the control frequency of 12% (p<0.001). Three patients were homozygous for the C282Y mutation, two of whom did not meet current clinical diagnostic criteria for expressed haemochromatosis. The proportion of patients with the H63D mutation did not differ from the reported control frequency. The mean transferrin saturation and serum ferritin concentration were similar in porphyria cutanea tarda patients who were homozygous normal and heterozygous for the C282Y mutation, but greater in both groups than previously reported in healthy controls. Seven (25.9%) patients were anti-HCV IgG positive. None of these patients carried the C282Y mutation. Porphyria cutanea tarda patients heterozygous for the C282Y mutation and patients with anti-HCV antibodies had elevated transferrin saturations and serum ferritin concentrations. The raised frequency of the C282Y mutation in porphyria cutanea tarda indicates that this mutation is likely to be a predisposing factor. However, abnormalities of iron indices also exist in porphyria cutanea tarda patients without mutations in HFE. Hepatitis C virus infection is likely to be another common precipitating factor for porphyria cutanea tarda which acts independently of the C282Y mutation.


Targeted regulation of MiR-98 on E2F1 increases chemosensitivity of leukemia cells K562/A02.
miRNA is a microRNA that negatively regulates protein expression at post-transcriptional or translational level. It is widely involved in the pathogenesis of tumors. miR-98 belongs to the let-7 family, and its overexpression can increase the sensitivity to drugs in solid cancer cells. However, the function of miR-98 in leukemia is still unclear. In this study, the effect of miR-98 on drug resistance and proliferation of leukemia cells were investigated. Real-time quantitative polymerase chain reaction analyzed the expression difference between miR-98 and E2F1 in leukemia cell lines, K562 and K562/A02. The downstream target gene of miR-98 was predicted by TargetScan; K562/A02 was transiently transfected with miR-98 mimic to upregulate the expression of miR-98; real-time quantitative polymerase chain reaction and Western blot were used to analyze the expression alterations of E2F1; cell counting kit-8 was used to evaluate the influence on K562/A02 proliferation and sensitivity to chemotherapeutic drugs; meanwhile, Western blot was used to analyze the expression of p21, Bax, matrix metalloproteinase 9 and ABCG2 proteins. E2F1 is one of the target genes of miR-98 proved by bioinformatics. Compared with the K562, the level of miRNA-98 expression was decreased in K562/A02, but the level of E2F1 expression was upregulated. Leukemia cell line K562/A02 was transfected with miR-98 mimic to upregulate the expression of miR-98, the expression of E2F1 was significantly decreased. After upregulating the miR-98 expression in K562/A02, the proliferation was weakened, and the sensitivity to chemotherapy was increased. Western blot showed that upregulated miR-98 expression increased the levels of p21 and BAX proteins in K562/A02 cells, and decreased the levels of matrix metalloprotease 9 and ABCG2 proteins, which were significantly different compared with those before miR-98 mimic transfection. In the leukemia drug-resistant cell line K562/A02, the targeted upregulated expression of miR-98 could decrease the proliferation of leukemia cells and improve the sensitivity to chemotherapeutics by inhibiting E2F1 expression. miR-98 might be a potential target for overcoming leukemia multidrug resistance.


Effect of quinacrine, a phospholipase A2 inhibitor on stress and chemically induced gastroduodenal ulcers.
Quinacrine, a phospholipase A2 inhibitor, has been studied for its ability to inhibit gastric secretion and to protect the gastric and duodenal mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without quinacrine treatment. Experimental gastric lesions were induced by water-immersion restraint stress, indomethacin and 80% ethanol in rats; whereas duodenal ulcers were produced by treatment of rats with cysteamine. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that quinacrine produces a dose-dependent inhibition of gastric acid secretion in rats. Pretreatment with quinacrine significantly attenuated the formation of stress-, indomethacin- and ethanol-induced gastric lesions. Quinacrine also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of quinacrine was associated with appreciable inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. These findings point towards the mediation of sulfhydryls in quinacrine-induced gastrointestinal cytoprotection. In conclusion, this study demonstrates that quinacrine possesses significant antiulcer and cytoprotective activity against various experimentally induced gastroduodenal lesions. Although the mechanism of action of quinacrine requires further evaluation, the experimental observations derived from this study may have future clinical relevance and therefore deserve to be investigated thoroughly.


What is PFAPA syndrome? Genetic clues about the pathogenesis.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in childhood. Recent studies report genetic susceptibility variants for PFAPA syndrome and the efficacy of tonsillectomy in a broader cohort of patients with recurrent stereotypical fever. In this review, we highlight the findings of these studies and what they may reveal about the pathogenesis of PFAPA. Newly identified genetic susceptibility loci for PFAPA suggest that it is a complex genetic disorder linked to Behçet's disease and recurrent aphthous ulcers. Patients who have PFAPA with some features of Behçet's disease have been reported. Moreover, the efficacy of tonsillectomy has now been described in patients who do not meet the full diagnostic criteria for PFAPA, although the immunologic profile in the tonsils is different from those with PFAPA. Factors that predict response to tonsillectomy are also reported. These findings highlight the heterogeneous phenotypes that may be related to PFAPA due to common genetic susceptibility or response to therapy. These relationships raise questions about how to define PFAPA and highlight the importance of understanding of the genetic architecture of PFAPA and related diseases.


Coordination between glottic adductor muscle and diaphragm EMG activity in fetal lambs in utero.
It has previously been reported that active glottic adduction is present during prolonged apneas but absent during periods of breathing movements in fetal lambs in utero. The present study was aimed at examining the precise coordination between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)]. Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an arterial catheter were surgically implanted in fetal lambs 123-142 days postconception. Polygraphic recordings were performed without sedation while the ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5; hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye-movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di EMG appeared. Altering blood gases did not modify these results. In conclusion, Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except in a few cases. These findings may have consequences for understanding the pathogenesis of mixed/obstructive apneas of prematurity.


Nuclear factor kappaB is required for peptide antigen-induced differentiation of a CD4+CD8+ thymocyte line.
NF-kappaB transcription factors are known to regulate the expression of a number of genes involved in T cell activation and function. Some evidence has suggested that they also play a role in T cell development. However, the role of NF-kappaB in Ag-induced thymocyte differentiation has not been directly addressed to date. Here we critically examine this role by employing DPK, a CD4+CD8+ thymocyte line that undergoes differentiation upon TCR engagement in a process that closely mimics positive selection. Expression of a degradation-resistant form of IkappaBalpha in DPK cells results in constitutive inhibition of NF-kappaB activity. We find that in the absence of NF-kappaB activity, MHC-peptide-induced differentiation of DPK is blocked. Furthermore, differentiation induced by a nonphysiologic stimulus, anti-TCR Ab, is greatly reduced. Altogether, our data indicate a requirement for NF-kappaB in the developmental changes associated with positive selection.


[Antiallergic effects of a novel compound, SWR-00151].
The effects of a newly synthesized compound, SWR-00151 (4-[2-[4-(1H-indol-3-yl)-1-piperidinyl)ethyl]-2(1H)-quinolinone), on experimental Type I allergic models were investigated. Results obtained were as follows: The compound (3 approximately 30 mg/kg, p.o.) dose-dependently inhibited 48-hr passive cutaneous anaphylaxis (PCA) in the rat. From the strong antagonism against the histamine-induced contraction of the isolated guinea pig ileum and the lack of suppressive effect on anaphylactic histamine release from rat peritoneal exudate cells, it is deduced that the compound's inhibitory action against PCA is due to antihistaminic action. Both gamma 1-rich serum- and IgE-rich serum-mediated experimental asthmas in the guinea pig were also considerably inhibited by a small dose (1 mg/kg, p.o.) of the compound. The inhibitory mechanism seems to be almost the same as that of the PCA because the compound did not show any effect on the experimental asthma in guinea pigs pretreated with H1- and H2-antihistaminics. In addition to that, it is well known that the model is largely mediated by anaphylactically released histamine. On the other hand, while ketotifen and oxatomide, which possess potent antihistaminic activity, modestly suppressed a rat experimental asthma SWR-00151 still demonstrated a substantial inhibitory activity, strongly suggesting that histamine does not play an important role in this asthma model. Serotonin was revealed to be partly responsible for the early phase of the reaction by the assessment with methysergide, an antiserotonergic, and SWR-00151 as well as oxatomide and ketotifen showed slight antagonism against serotonin in high concentrations (10(-6) and 10(-5) M) in vitro. When thromboxane (TX) B2 in the plasma was measured during the reaction, significant increased levels of the chemical mediator were found, which were obviously prevented by the treatment with SRW-00151. From these results, SWR-00151 is expected to be a drug effective for the treatment of asthma through mechanisms not only of antihistaminic action but also through inhibition of anaphylactic formation/release of other mediators like TXA2.


Expression of PTEN in ovarian epithelial tumors and its relation to tumor behavior and growth.
To evaluate the expression of tumor suppressor gene phosphatase and tensin homologue on chromosome 10 (PTEN) in ovarian epithelial tumors and its correlation with tumor growth and clinicopathologic features in ovarian adenocarcinomas. Immunohistochemical staining with anti-PTEN antibody was performed in 54 adenocarcinomas and 23 borderline tumors of the ovary. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling, and proliferative cells were visualized by staining with Ki-67 antibody. Reduced PTEN expression was significantly higher among the adenocarcinomas than the borderline tumors (p < 0.001). Reduced PTEN expression in adenocarcinomas did not correlate with International Federation of Obstetrics and Gynecology (FIGO) stage. The Ki-67 index (KI) and apoptotic index were significantly higher in adenocarcinomas as compared with borderline tumors (p < 0.001). Tumors with reduced PTEN expression in ovarian adenocarcinomas had a significantly higher KI than those with normal PTEN expression (p < 0.01). By univariate analysis, FIGO stage and histologic type correlated with survival. However, FIGO stage was the only independent prognostic factor by multivariate analysis. Our results suggest that alteration of the PTEN gene may be associated with malignant transformation of ovarian epithelial tumors. The PTEN gene seems to be a negative regulator of cell proliferation in ovarian adenocarcinomas.


Benign multicystic peritoneal mesothelioma treated with laparoendoscopic single site surgery: a case report and review of the literature.
Benign multicystic peritoneal mesothelioma (BMPM) is rare and difficult to diagnose before surgery. We report a case of BMPM incidentally discovered during laparoendoscopic single site surgery (LESS) for treatment of a pelvic mass. A 47-year-old Korean menopaused woman presented to our outpatient clinic with a pelvic mass. She had a history of right ovary cystectomy with adhesiolysis at a local hospital in 2010. Imaging study of the pelvis revealed a multilocular cystic mass. LESS was performed and multiple grapelike clusters of cysts were seen in the uterus, cul-de-sac, both adnexa, pelvic wall, and omentum. The appendix was grossly free. Frozen biopsy confirmed BMPM. Excision of multiple cyst clusters of cysts, resection of the uterus with both adnexa, appendectomy, omentectomy, and adhesiolysis were performed with LESS. She is well for 2 years with no recurrence. BMPM should be included in the differential diagnosis when small multichamber cystic mass is found on ultrasonography.


Effects of nitric oxide on large-conductance Ca2+ -activated K+ currents in human cardiac fibroblasts through PKA and PKG-related pathways.
The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca2+ -activated K+ (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) plays a key role. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well-maintained outward K+ currents without marked inactivation throughout the test pulse period and detected outward rectification in the I-V curve; these are all characteristics that are typical of KCa currents. These currents were blocked with iberiotoxin (IBTX, a BKCa blocker) but not with TRAM-34 (an IKCa blocker). The amplitudes of the currents were increased with SNAP (an NO donor), and these increases were inhibited with IBTX. The SNAP-stimulating effect on the BKCa currents was blocked by pretreatment with KT5823 (a protein kinase G [PKG] inhibitor) or 1 H-[1,-2, -4] oxadiazolo-[4,-3-a] quinoxalin-1-one (ODQ; a soluble guanylate cyclase inhibitor). Additionally, 8-bromo-cyclic guanosine 3',5'-monophosphate (8-Br-cGMP) stimulated the BKCa currents, and pretreatment with KT5720 (a protein kinase A [PKA] inhibitor) and SQ22536 (an adenylyl cyclase inhibitor) blocked the NO-stimulating effect on the BKCa currents. Furthermore, 8-bromo-cyclic adenosine 3',5'-monophosphate (8-Br-cAMP) activated the BKCa currents. These data suggest that BKCa current is the main subtype of the KCa current in HCFs and that NO enhances these currents through the PKG and PKA pathways.


Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 +/- Mutant Mice.
In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2 +/- heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive, and parental behaviors. Interestingly, some of these deficits are displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue. This analyses revealed putative sex differences expression of a host of proteins implicated in neuronal communication, connectivity, and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.


Molecular dynamics simulations of capillary rise experiments in nanotubes coated with polymer brushes.
The capillary filling of a nanotube coated with a polymer brush is studied by molecular dynamics simulations of a coarse-grained model, assuming various conditions for the fluid-wall and fluid-brush interactions. Whereas the fluid is modeled by simple point particles interacting with Lennard-Jones forces, the (end-grafted, fully flexible) polymers that form the brush coating are described by a standard bead-spring model. Our experiments reveal that capillary filling is observed even for walls that would not be wetted by the fluid, provided the polymer brush coating itself wets. Generally, it is found that the capillary rise always proceeds through a t1/2 law with time t while the underlying molecular mechanism differs for wettable and nonwettable walls. For wettable walls, fluid imbibition is compatible with the Lucas-Washburn mechanism whereby the total influx of matter drops steadily with growing chain length N and the meniscus speed goes through a minimum at intermediate chain lengths. Moreover, because of flow, the polymer brush reorganizes its structure by forming a dense plug of chain segments under the meniscus that follows the meniscus in its motion. When the tube wall does not wet, one observes no meniscus formation for short chains although the fluid seeps through the wet brush. For a brush coating with longer chains, axial segregation between the brush segments and the fluid occurs by a kind of diffusive spreading, reminiscent of invasion percolation transport in a random medium, leading to the formation of a moving meniscus. For even longer chains that reach the tube axis, the rise of a meniscus with vanishing curvature-like imbibition in a porous medium is observed to take place.


Two new genera of predatory katydids (Orthoptera: Tettigoniidae: Meconematinae) from the Amazon rainforest.
Meconematinae comprise small predatory katydids. There are currently seven genera and 58 species recorded for the Neotropical region. Two new genera of Phlugidini are described from the Amazon region, Arboraptor gen. nov., type species Arboraptor viridis sp. nov., and Tyrannoraptor gen. nov., type species Tyrannoraptor arboreus (Nickle, 2003) n. comb. A key to the Neotropical genera of Phlugidini is included and we provide a map showing the known distribution plus comments on their behavior observed during fieldwork.


Paliperidone Long-Acting Plasma Level Monitoring and a New Method of Evaluation of Clinical Stability.
The second generation long-acting antipsychotics can be a pharmacologic strategy, both in the early phase of illness and in the case of low compliance. The aim of the study was to evaluate the clinical efficacy and tolerability of one monthly injection of paliperidone palmitate (PP1M), paliperidone plasma levels (PLs), and the clinical outcome. 21 outpatients, affected by Schizophrenia or Schizoaffective Disorder, were recruited. PP1M started with 150 mg on day 1 and 100 mg on day 8. Following patients were given a dosage ranging from 50 mg to 150 mg every 28 days. At baseline, and then monthly, patients were clinically evaluated. BPRS and PANSS total score showed a statistically significant decrease from T2 (after 2 months) to T12 (after 12 months). The PLs steady-state was approximatively reached after the fifth injection (T4). All the patients showed a clinical stabilization: BPRS and PANSS scores showed a significant improvement from T2. PLs data seems to suggest the initial possibility of an oral supplementation, although clinical evaluation demonstrated no relapse during the study.


Analysis of exercise-induced Na+-K+ exchange in rat skeletal muscle in vivo.
We aimed to quantify the Na(+)-K(+) exchange occurring during exercise in rat skeletal muscle in vivo. Intracellular Na(+) and K(+) content, Na(+) permeability ((22)Na(+) influx), Na(+)-K(+) pump activity (ouabain-sensitive (86)Rb(+) uptake) and Na(+)-K(+) pump alpha(2) subunit content ([(3)H]ouabain binding) were measured. Six-week-old rats rested (control animals) or performed intermittent running for 10-60 min and were then killed or were killed at 15 or 90 min following 60 min exercise. In the soleus muscle, intracellular Na(+) was 80% higher than in control rats after 60 min exercise, was still elevated (38%) after 15 min rest and returned to control levels after 90 min rest. Intracellular K(+) showed corresponding decreases after 15-60 min exercise, returning to control levels 90 min postexercise. Exercise induced little change in Na(+) and K(+) in the extensor digitorum longus muscle (EDL). In soleus, the exercise-induced rise in Na(+) and reduction in K(+) were augmented by pretreatment with ouabain or by reducing the content of muscular Na(+)-K(+) pumps by prior K(+) depletion of the animals. Fifteen minutes after 60 min exercise, ouabain-sensitive (86)Rb(+) uptake in the soleus was increased by 30% but was unchanged in EDL, and there was no effect of exercise on [(3)H]ouabain binding measured in vitro or in vivo in either muscle. In conclusion, in the soleus, in vivo exercise induces a rise in intracellular Na(+), which reflects the excitation-induced increase in Na(+) influx and leads to augmented Na(+)-K(+) pump activity without apparent change in Na(+)-K(+) pump capacity.


Therapeutic Effect of Tetrapanax papyriferus and Hederagenin on Chronic Neuropathic Pain of Chronic Constriction Injury of Sciatic Nerve Rats Based on KEGG Pathway Prediction and Experimental Verification.
Hederagenin is one of the main components of Tetrapanax papyriferus, and Tetrapanax papyriferus is one of the ingredients of Danggui Sini decoction. To explore whether Tetrapanax papyriferus and hederagenin can alleviate mechanical pain, thermal hyperalgesia, and cold pain at the same time, we comprehensively investigated the effects of two drugs on the levels of p38 MAPK phosphorylation, TRP proteins, and IL1β, IL6, and TNF-α in serum. Firstly, we obtained pain-related targets and performed KEGG pathway enrichment on these targets. Then, 42 SD rats were separated randomly into six groups: sham operation group, CCI group, pregabalin group, mecobalamin group, Tetrapanax papyriferus group, and hederagenin group. All drugs were given orally. Rats in the sham operation group and CCI group were gavaged with saline. Rats in the pregabalin group were given pregabalin, while rats in the mecobalamin group were given mecobalamin. Rats in the Tetrapanax papyriferus group were given Tetrapanax papyriferus, while rats in the hederagenin group were given hederagenin. Besides, we conducted behavioral tests including acetone test, hot plate experiment, and von Frey filaments, and then dorsal root ganglion neurons were taken out on the 21st day after operation. Then, western blot, ELISA, and hematoxylin-eosin staining were conducted. Rats in the CCI group were more sensitive to hyperalgesia and allodynia to mechanical and thermal stimuli, as well as cold pain. All four drugs could relieve these pains. Pregabalin, mecobalamin, and Tetrapanax papyriferus can reduce the levels of IL1β, IL6, and TNF-α in serum compared to those of the CCI group. The expression of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in DRG increased evidently on the 21st day after the operation in the CCI group. All four drugs could reduce the expressions of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in dorsal root ganglion compared to those of the CCI group. Tetrapanax papyriferus and hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins.


Uncommon Presentation of Cystic Fibrosis: A Case Report and Literature Review.
Cystic fibrosis (CF) is a multiorgan disease, caused by autosomal recessive (AR) mutations in the cystic fibrosis transmembrane regulator (CFTR) acting primarily as a chloride channel. CF is most commonly diagnosed in Caucasian populations. Common clinical presentations in pediatric patients include chronic cough, respiratory tract infections such as pneumonia, digestive symptoms, and stunted growth, and malnutrition due to gastrointestinal malabsorption and pancreatic insufficiency. Excessive sweat sodium chloride losses due to dysfunctional sweat glands in CFTR result in volume contraction and secondary hyperaldosteronism leading to renal potassium losses and metabolic alkalosis. Hypokalemic hypochloremic metabolic alkalosis is a known but uncommon presenting sign of the disease, documented as pseudo Bartter syndrome. Common mutations in the CFTR gene are now included in prenatal genetic screening programs. We describe the case of an infant of African descent with normal prenatal screening who presented with severe hypokalemic hypochloremic metabolic alkalosis and was diagnosed with CF with further genetic confirmation of the diagnosis.


All-terrain self-leveling wheelchair.
Limited mobility is something that affects approximately 6.8 million Americans. Approximately 1.7 million are using wheelchairs or scooters of some kind to enhance mobility. Everyday obstacles present a challenge to those in a wheelchair. Also, outdoor environments such as campsites, lakes, or even grass fields provide additional challenges for those with limited mobility. This project provides a solution to some of the limitations faced by those in wheelchairs. The wheels and tires of the wheelchair allow navigation through most terrains such as grass, gravel, and sand. Furthermore, as a wheelchair climbs or descends a hill it becomes unstable and the user risks tipping the wheelchair causing injury or even death. The self-leveling wheelchair uses an accelerometer to determine its angle of inclination and depending on user interface choices will display the angle or raise the seat with linear actuators to keep the seat level. This will keep the center of gravity towards the front of the chair when going up a hill and towards the back of the chair when going down a hill. This enhanced stability will give the user the confidence and ability to go places where most traditional wheelchairs can not. The chair has the ability to self-level at up to 45 degree and can provide a manual lift of 6 inches. The design presented in this report is patent pending.


[Clinical research XXIII. From clinical judgment to meta-analyses].
Systematic reviews (SR) are studies made in order to ask clinical questions based on original articles. Meta-analysis (MTA) is the mathematical analysis of SR. These analyses are divided in two groups, those which evaluate the measured results of quantitative variables (for example, the body mass index -BMI-) and those which evaluate qualitative variables (for example, if a patient is alive or dead, or if he is healing or not). Quantitative variables generally use the mean difference analysis and qualitative variables can be performed using several calculations: odds ratio (OR), relative risk (RR), absolute risk reduction (ARR) and hazard ratio (HR). These analyses are represented through forest plots which allow the evaluation of each individual study, as well as the heterogeneity between studies and the overall effect of the intervention. These analyses are mainly based on Student's t test and chi-squared. To take appropriate decisions based on the MTA, it is important to understand the characteristics of statistical methods in order to avoid misinterpretations.


[Treatment of sclerodermic esophagitis: value of duodenal diversion].
Between 1985 and 1990, six patients were operated on using duodenal diversion for reflux esophagitis with scleroderma. Duodenal diversion was performed twice as initial procedure and 4 times as treatment of unsuccessful antireflux procedure performed ten years previously. Duodenal diversion was associated with truncal vagotomy. In cases of reoperation the initial reconstruction procedure was removed. An esophageal stricture was resected in one case. One patient with previous truncal vagotomy and pyloroplasty underwent supra papillary diversion. There was no postoperative death. The mean follow-up was 28 months with one patient lost to follow-up. For 4 patients, the postoperative weight gain was 10 per cent. Abnormalities of lower esophageal motility in scleroderma account for the poor results after classical antireflux procedures. In these cases duodenal diversion is indicated as primary treatment. In cases of reoperation removal of the initial anti-reflux device is required in association with duodenal diversion.


Wegener's granulomatosis masquerading as a renal cancer: a case report and review of the literature.
A 32 year-old man presented with sinusitis, proteinuria, mononeuritis multiplex, very increased acute phase proteins. Anti-PR3 ANCA were detected and Wegener's granulomatosis (WG) was diagnosed. As abdominal tomodensitometry detected a tumoral process of the left kidney, a paraneoplastic vasculitis associated with a renal cancer was suspected. Biopsy of the mass showed fibrosis, inflammatory infiltrates and necrotizing granulomas. No malignant cells were detected. The outcome was favourable after administration of methylprednisolone and cyclophosphamide. Characteristics of the nine previously reported renal inflammatory pseudotumors associated with WG are discussed.


[Effectiveness and patient tolerance of screening colonoscopy -- first results].
In Germany screening colonoscopy was introduced into the national program on colorectal cancer prevention in October 2002 for asymptomatic subjects older than 55 years. It is the aim of this program to reduce the rate of mortality of colorectal cancer (CRC) during the next decade. Up to now no data are available concerning the outcome and patient tolerance of screening colonoscopy. Patients were enrolled in the prospective study between October 2002 and June 2003. The diagnoses from colonoscopy and complications were recorded. A short interview provided information on individual family risks of CRC. During June 2003 all subjects were handed a questionnaire to evaluate their satisfaction and tolerance concerning screening colonoscopy. All subjects were offered sedation (Disoprivan: Propofol). A total of 1117 subjects (776 [69.5 %] female, 341 [30.5 %] male) underwent screening colonoscopy; age: 64.3 +/- 6.9 years. 1104 (98.8 %) requested sedation. In 1090 cases (97.6 %) colonoscopy was completed to the cecum (photographic documentation of cecal landmarks). A total of 11 patients had invasive cancer (1 %), 4 of these had adenomas containing invasive carcinoma. The stage was T1/N0 or T2/N0. A total of 138 (12.4 %) patients had 168 polypoid lesions, which were treated by complete polypectomy. 402 small polypoid lesions (< 0.5 cm) were only detected by biopsy. In this group 233 adenomas (20.9 %) were found. Complications were: 1 perforation and 4 haemorrhages after polypectomy. Patient tolerance was very high. 99.4 % of all subjects agreed to a control colonoscopy or recommended screening colonoscopy to their relatives and friends. Screening colonoscopy is an effective and well-accepted method in our unit for gastroenterology. The high prevalence of adenoma and invasive carcinoma suggests that screening colonoscopy should be provided for all persons at the age of 55, especially for men.


Synthesis of PtRu5(CO)14(PBu(t)3)(mu-H)2(mu6-C) and its reactions with Pt(PBut3)2, HGePh3, and HSnPh3.
Reaction of PtRu5(CO)15(PBut3)(C), 3, with hydrogen at 97 degrees C yielded the new dihydride-containing cluster compound PtRu5(CO)14(PBut3)(mu-H)2(mu6-C), 5. Compound 5 was characterized crystallographically and was shown to contain an octahedral cluster consisting of one platinum and five ruthenium atoms with a carbido ligand in the center. Two hydrido ligands bridge two oppositely positioned PtRu bonds. Compound 5 reacts with Pt(PBut3)2 to yield Pt2Ru5(CO)14(PBut3)2(mu-H)2(mu6-C), 6, a Pt(PBut3) adduct of 5, by adding a Pt(PBut3) group as a bridge across one of the Ru-Ru bonds in the square base of the Ru5 portion of the cluster. Compound 6 is dynamically active on the NMR time scale by a mechanism that appears to involve a shifting of the Pt(PBut3) group from one Ru-Ru bond to another. Two new complexes, PtRu5(CO)13(PBut3)(mu-H)3(GePh3)(mu5-C), 7, and PtRu5(CO)13(PBut3)(mu-H)2(mu-GePh2)(mu6-C), 8, were obtained from the reaction of 5 with HGePh3. The cluster of 7 has an open structure in which the Pt(PBut3) group bridges an edge of the square base of the square pyramidal Ru5 cluster. Compound 7 also has three bridging hydrido ligands and one terminal GePh3 ligand. When heated to 97 degrees C, 7 is slowly converted to 8 by cleavage of a phenyl group from the GePh3 ligand and elimination of benzene by its combination with one of the hydrido ligands. The PtRu5 metal cluster of 8 has a closed octahedral shape with a GePh2 ligand bridging one of the Ru-Ru bonds. Two tin-containing compounds, PtRu5(CO)13(PBut3)(mu-H)3(SnPh3)(mu5-C), 9, and PtRu5(CO)13(PBut3)(mu-H)2(mu-SnPh2)(mu6-C), 10, which are analogous to 7 and 8 were obtained from the reaction of 5 with HSnPh3.


Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Fas lpr/lpr mice.
Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas lpr/lpr mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of "oocyte cumulus complexes" found in the ampulla was macroscopically counted, and that of "ovulated oocytes" was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas lpr/lpr mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas lpr/lpr mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas lpr/lpr mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.


The Effects of Fiber Inclusion on Pet Food Sensory Characteristics and Palatability.
The objectives of this study were to determine (a) the influence of fiber on the sensory characteristics of dry dog foods; (b) differences of coated and uncoated kibbles for aroma and flavor characteristics; (c) palatability of these dry dog foods; and (d) potential associations between palatability and sensory attributes. A total of eight fiber treatments were manufactured: a control (no fiber addition), guava fiber (3%, 6%, and 12%), sugar cane fiber (9%; large and small particle size), and wheat bran fiber (32%; large and small particle size). The results indicated significant effects of fibers on both flavor and texture properties of the samples. Bitter taste and iron and stale aftertaste were examples of flavor attributes that differed with treatment, with highest intensity observed for 12% guava fiber and small particle size sugar cane fiber treatments. Fracturability and initial crispness attributes were lowest for the sugar cane fiber treatments. Flavor of all treatments changed after coating with a palatant, increasing in toasted, brothy, and grainy attributes. The coating also had a masking effect on aroma attributes such as stale, flavor attributes such as iron and bitter taste, and appearance attributes such as porosity. Palatability testing results indicated that the control treatment was preferred over the sugar cane or the wheat bran treatment. The treatment with large sugarcane fiber particles was preferred over the treatment with small particles, while both of the wheat bran treatments were eaten at a similar level. Descriptive sensory analysis data, especially textural attributes, were useful in pinpointing the underlying characteristics and were considered to be reasons that may influence palatability of dog foods manufactured with inclusion of different fibers.


Preparation of a selective L-phenylalanine imprinted polymer implicated in patients with phenylketonuria.
Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer (MIP) against l-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid (ESIF). The MIP for l-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid (MAA), as a functional monomer, and ethylene glycol dimethacrylate (EGDMA), as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran (THF), chloroform, toluene and dimethyl sulfoxide (DMSO). The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM. The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MIP was significantly more than the former binding to NIP in EISF (P≤0.05). Moreover, in comparison with NIP and control group, MIP showed a better selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria. Our findings suggest that the MIP against Phe prepared with acetonitrile, showed a good selectivity and binding, which caused a reduction of blood Phe concentration in enzymatic simulated intestinal fluid and human serum sample of Phenylketonuria.


Filbertone: A Review.
This comprehensive review of filbertone, a principal flavor compound of hazelnut, evaluates the current state of the art of all relevant aspects of the title molecule: its occurrence and properties, laboratory preparation and bulk synthesis, analytical issues regarding stereochemistry and purity, sensory evaluation, and practical uses. Comparisons are made between different synthetic approaches, and a critical assessment of various applications is presented.


Antibodies against bacterial lipopolysaccharides in Japanese patients with ankylosing spondylitis.
We investigated IgG, IgA and IgM class specific antibodies to five bacterial (Klebsiella pneumoniae, Escherichia coli, Salmonella enteritidis, Salmonella typhimurium and Shigella flexneri) lipopolysaccharides (LPS) by enzyme-linked immunosorbent assay in 144 Japanese patients with ankylosing spondylitis (AS). AS patients had significantly elevated IgA antibodies to K. pneumoniae LPS, Salmonella enteritidis LPS and Salmonella typhimurium LPS; however, there was no correlation between antibody level to LPS and acute-phase reactants, erythrocyte sedimentation rate and serum C-reactive protein.


Endurance training: an effective and safe treatment for patients with LGMD2I.
We studied the effect of aerobic training on conditioning in patients with limb-girdle muscular dystrophy type 2I (LGMD2I). Nine patients with LGMD2I cycled fifty 30-minute sessions at 65% of their maximal oxygen uptake over 12 weeks. Training significantly improved work capacity, paralleled by self-reported improvements. Creatine kinase levels did not increase significantly, and muscle morphology was unaffected. Moderate-intensity endurance training is a safe method to increase exercise performance and daily function in patients with LGMD2I.


Lysoglyceroglycolipids Improve the Intestinal Absorption of Micellar Fucoxanthin by Caco-2 Cells.
To improve the intestinal absorption of fucoxanthin, we evaluated the effects of dietary glyceroglycolipids on the uptake and secretion of fucoxanthin solubilized in mixed micelles by human intestinal Caco-2 cells. Although digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol suppressed fucoxanthin uptake and secretion, their lyso-types, digalactosylmonoacylglycerol and sulfoquinovosylmonoa cylglycerol, remarkably enhanced them. Thus, some dietary glyceroglycolipids may be potential enhancers of fucoxanthin bioavailability in humans.


The epidemiology of St. Louis encephalitis in Corpus Christi, Texas, 1966.
In the summer of 1966, an epidemic of St. Louis encephalitis occurred in Corpus Christi, Texas, coincident with one occurring in Dallas about 563 km to the north. Among the 76 cases confirmed in Corpus Christi, there were two deaths; the attack rate was 41.0 per 100,000. In contrast with a concurrent outbreak in Dallas and the 1964 outbreak in Houston, attack rates were much higher in populations of the upper socioeconomic districts. This distribution may have resulted from the combined effects of an unusual concentration of vector mosquito breeding sites in storm sewers in the upper socioeconomic districts and a higher degree of residual immunity in the residents of the lower socioeconomic areas.


Type I IFN protects against murine lupus.
Both the type I (IFN-alpha beta) and type II (IFN-gamma) IFNs have been heavily implicated in the pathogenesis of systemic lupus erythematosus. To test the relative roles of these systems, congenic lupus-prone MRL/CD95(lpr/lpr) (MRL/lpr) mice lacking the type I IFN receptor (IFN-RI), type II IFN receptor (IFN-RII), or both, were derived. As expected, deficiency for IFN-RII protected MRL/lpr mice from the development of significant autoimmune-associated lymphadenopathy, autoantibodies, and renal disease. However, deficiency for the IFN-RI surprisingly worsened lymphoproliferation, autoantibody production, and end organ disease; animals doubly deficient for IFN-RI and IFN-RII developed an autoimmune phenotype intermediate between wild-type and IFN-RII-deficient animals, all correlating with an ability of type I IFN to suppress MRL B cell activation. Thus, type I IFNs protect against both the humoral and end organ autoimmune syndrome of MRL/lpr mice, independent of IFN-gamma. These findings warrant caution in the use of type I IFN antagonists in the treatment of autoimmune diseases and suggest further investigation into the interplay between the types I and II IFNs during the ontogeny of pathogenic autoantibodies.


Separation of overlap and collateral perfusion of ischemic canine myocardium: important considerations in the analysis of vasodilator-induced coronary steal.
Coronary steal was studied in dogs with a left anterior descending (LAD) coronary artery occlusion by use of a special technique to exclude contamination from overlapping circulations with true collateral blood flow. Different degrees of vasodilation in nonischemic myocardium were produced by the selective coronary dilator, chromonar, at a constant heart rate and aortic blood pressure. A map of the ischemic area was made, and criteria used to identify ischemic tissue samples included: (1) all samples within the LAD perfusion area, as defined by a dye technique; (2) tissue samples with blood flows less than 25% normal area flow; (3) samples from within the central ischemic zone; and (4) tissue samples with overlap blood flow less than 2% normal area flow. When criteria 1 and 2 were used to identify ischemic myocardium, chromonar (5 and 7.5 mg/kg, i.v.) produced no change in ischemic blood flow. On the other hand, when tissue samples from the central ischemic zone or those which had less than 2% overlap flow (criteria 3 and 4) were used to identify ischemic myocardium, chromonar produced a dose-related decrease (p less than 0.01) in transmural collateral perfusion (25 +/- 4 and 33 +/- +/- 5;33 +/- 3 and 41 +/- 6%, respectively). Other indices of collateral function, peripheral coronary pressure (23 +/- 4 and 25 +/- 3%), retrograde flow (20 +/- 3 and 26 +/- 4%), and retrograde conductance (21 +/- 4 and 30 +/- 4%), also decreased significantly. These results indicate that moderate to maximal coronary vasodilation produces a true coronary steal in the absence of changes in aortic pressure and heart rate. In addition, these data demonstrate that significant amounts of overlap flow are contained in superior, inferior, and lateral borders of the ischemic zone, and that strict criteria to identify ischemic myocardium are needed when studying the effect of drugs on true coronary collateral blood flow.


First Complete Genome Sequence of Corynebacterium riegelii.
Here, we report the first complete genome sequence of Corynebacterium riegelii strain PUDD_83A45, isolated from the urine of a patient with urinary tract infection. The genome measured 2.56 Mb and contained no plasmid.


Determination of carbamazepine in human urine and serum samples by high-performance liquid chromatography with post-column Ru(bipy)2(3+)-Ce(SO4)2 chemiluminescence detection.
A novel, sensitive and rapid CL method coupled with high-performance liquid chromatography separation for the determination of carbamazepine is described. The method was based on the fact that carbamazepine could significantly enhance the chemiluminescence of the reaction of cerium sulfate and tris(2,2-bipyridyl) ruthenium(II) in the presence of acid. The chromatographic separation was performed on a Kromasil® (Sigma-Aldrich) TM RP-C18 column (id: 150 mm × 4.6 mm, particle size: 5 µm, pore size: 100 Å) with a mobile phase consisting of methanol-water-glacial acetic acid (70:29:1, v/v/v) at a flowrate of 1.0 mL/min, the total analysis time was within 650 s. Under optimal conditions, CL intensity was linear for carbamazepine in the range 2.0 × 10(-8) ~ 4.0 × 10(-5) g/mL, with a detection limit of 6.0 × 10(-9) g/mL (S/N = 3) and the relative standard detection was 2.5% for 2.0 × 10(-6) g/mL (n = 11). This method was successfully applied to the analysis of carbamazepine in human urine and serum samples. The possible mechanism of the CL reaction is also discussed briefly.


Reversible Switch in Charge Storage Enabled by Selective Ion Transport in Solid Electrolyte Interphase.
Solid-electrolyte interphases (SEIs) in advanced rechargeable batteries ensure reversible electrode reactions at extreme potentials beyond the thermodynamic stability limits of electrolytes by insulating electrons while allowing the transport of working ions. Such selective ion transport occurs naturally in biological cell membranes as a ubiquitous prerequisite of many life processes and a foundation of biodiversity. In addition, cell membranes can selectively open and close the ion channels in response to external stimuli (e.g., electrical, chemical, mechanical, and thermal), giving rise to "gating" mechanisms that help manage intracellular reactions. We wondered whether the chemistry and structure of SEIs can mimic those of cell membranes, such that ion gating can be replicated. That is, can SEIs realize a reversible switching between two electrochemical behaviors, i.e., the ion intercalation chemistry of batteries and the ion adsorption of capacitors? Herein, we report such SEIs that result in thermally activated selective ion transport. The function of open/close gate switches is governed by the chemical and structural dynamics of SEIs under different thermal conditions, with precise behaviors as conducting and insulating interphases that enable battery and capacitive processes within a finite temperature window. Such an ion gating function is synergistically contributed by Arrhenius-activated ion transport and SEI dissolution/regrowth. Following the understanding of this new mechanism, we then develop an electrochemical method to heal the SEI layer in situ. The knowledge acquired in this work reveals the possibility of hitherto unknown biomimetic properties of SEIs, which will guide us to leverage such complexities to design better SEIs for future battery chemistries.


Effects of maternal bisphosphonate use on fetal and neonatal outcomes.
A review of case reports and other published data on fetal and neonatal outcomes associated with maternal use of bisphosphonate medications is presented. Bisphosphonates can persist in the bone matrix for years, even after therapy is discontinued, potentially resulting in fetal bisphosphonate exposure during pregnancy. Adverse effects of bisphosphonates on fetal outcomes have been observed in animal studies, but the bisphosphonate doses administered were much higher than those typically used in clinical practice. A literature search of PubMed (1946-May 2014) and ToxNet identified 15 articles describing the use of bisphosphonate medications by women before and/or during pregnancy (in total, the articles described 65 mother-child pairs); the agents used included alendronate, ibandronate, risedronate, etidronate, pamidronate, tiludronate, and zoledronic acid, with the reported durations of use ranging from one-time treatments to periods of months or years. Adverse outcomes possibly attributable to bisphosphonate use included marginal decreases in gestational age and birth weight and transient neonatal electrolyte abnormalities (e.g., hypocalcemia, hypercalcemia, hyperphosphatemia); however, no long-term health consequences were reported in any infant. Overall, the available published data appear to indicate that maternal bisphosphonate use does not pose a high risk of fetal or neonatal harm. Nonetheless, in cases of known or suspected fetal bisphosphonate exposure, monitoring for neonatal hypocalcemia and associated neuromuscular and cardiac symptoms is advised. A limited body of published data suggests that maternal use of bisphosphonates before or during pregnancy does not have serious fetal or neonatal adverse effects.


Large deviation function for a driven underdamped particle in a periodic potential.
Employing large deviation theory, we explore current fluctuations of underdamped Brownian motion for the paradigmatic example of a single particle in a one-dimensional periodic potential. Two different approaches to the large deviation function of the particle current are presented. First, we derive an explicit expression for the large deviation functional of the empirical phase space density, which replaces the level 2.5 functional used for overdamped dynamics. Using this approach, we obtain several bounds on the large deviation function of the particle current. We compare these to bounds for overdamped dynamics that have recently been derived, motivated by the thermodynamic uncertainty relation. Second, we provide a method to calculate the large deviation function via the cumulant generating function. We use this method to assess the tightness of the bounds in a numerical case study for a cosine potential.


Psychological treatment of generalised anxiety disorder. A review of the clinical significance of results in outcome studies since 1980.
Comparative outcome studies of generalised anxiety disorder suggest that psychological therapy is a potentially valuable alternative to anxiolytic medication. However, on average psychological therapy results in modest improvements in symptoms, with about 50% of patients achieving normal functioning. Limited follow-up data indicate that these changes are maintained over six months. Cognitive therapy appears to be most effective, although comparisons with other therapies are limited and non-specific factors are clearly important. There is also evidence of considerable variability in outcome between studies, with the best results obtained with patients who are free of anxiolytic medication and recruited directly from primary care or other non-psychiatric settings. The effects on outcome of patient characteristics known to be associated with more severe illness and complexity of clinical presentation have yet to be explored. A balanced appraisal of the value of psychological therapy with this common condition requires a fuller description of sample characteristics and more systematic investigation of the clinical significance of treatment effects over the long term.


Idiopathic sclerosing encapsulating peritonitis in an adult male with intermittent subacute bowel obstruction, preoperative multidetector-row CT (MDCT) diagnosis.
Idiopathic sclerosing encapsulating peritonitis (SEP) is a rare cause of intestinal obstruction that is characterised by a thick greyish-white fibrotic membrane encasing the small bowel. It is difficult to make a definite preoperative diagnosis. We report a successfully treated case of a 42-year-man, presented with sub acute small bowel obstruction caused by SEP. CT showed characteristic findings of small bowel loops congregated to the center of the abdomen encased by a soft-tissue density mantle. He had undergone adhesiolysis and uneventful postoperative period. A high index of clinical suspicion may be generated by the recurrent character of small bowel obstruction combined with relevant imaging findings and lack of other plausible aetiologies. Clinicians must rigorously pursue a preoperative diagnosis, as it may prevent a surprise upon laparotomy and result in proper management.


Purification and properties of the myo-inositol-binding protein from a Pseudomonas sp.
A myo-inositol-binding protein was isolated from a Pseudomonas sp. soil isolate and was purified to homogeneity. Its molecular weight is 30,000, and it has a single binding site. The amino acid analysis showed that the protein contains three tryptophan residues and no cysteine. Tryptophan residues seem to be involved in the binding of the ligand, as shown by the modification of the fluorescence spectra and by the fact that oxidation of tryptophan residues with N-bromosuccinimide abolished the binding of myo-inositol. Sequence analysis of the N-terminal segment of 37 amino acids showed that 13 are conserved when compared with the galactose-binding protein of Escherichia coli.


An acute bout of exercise modulates both intracortical and interhemispheric excitability.
Primary motor cortex (M1) excitability is modulated following a single session of cycling exercise. Specifically, short-interval intracortical inhibition and intracortical facilitation are altered following a session of cycling, suggesting that exercise affects the excitability of varied cortical circuits. Yet we do not know whether a session of exercise also impacts the excitability of interhemispheric circuits between, and other intracortical circuits within, M1. Here we present two experiments designed to address this gap in knowledge. In experiment 1, single and paired pulse transcranial magnetic stimulation (TMS) were used to measure intracortical circuits including, short-interval intracortical facilitation (SICF) tested at 1.1, 1.5, 2.7, 3.1 and 4.5 ms interstimulus intervals (ISIs), contralateral silent period (CSP) and interhemispheric interactions by measuring transcallosal inhibition (TCI) recorded from the abductor pollicus brevis muscles. All circuits were assessed bilaterally pre and two time points post (immediately, 30 min) moderate intensity lower limb cycling. SICF was enhanced in the left hemisphere after exercise at the 1.5 ms ISI. Also, CSP was shortened and TCI decreased bilaterally after exercise. In Experiment 2, corticospinal and spinal excitability were tested before and after exercise to investigate the locus of the effects found in Experiment 1. Exercise did not impact motor-evoked potential recruitment curves, Hoffman reflex or V-wave amplitudes. These results suggest that a session of exercise decreases intracortical and interhemispheric inhibition and increases facilitation in multiple circuits within M1, without concurrently altering spinal excitability. These findings have implications for developing exercise strategies designed to potentiate M1 plasticity and skill learning in healthy and clinical populations.


Nano-palladium is a cellular catalyst for in vivo chemistry.
Palladium catalysts have been widely adopted for organic synthesis and diverse industrial applications given their efficacy and safety, yet their biological in vivo use has been limited to date. Here we show that nanoencapsulated palladium is an effective means to target and treat disease through in vivo catalysis. Palladium nanoparticles (Pd-NPs) were created by screening different Pd compounds and then encapsulating bis[tri(2-furyl)phosphine]palladium(II) dichloride in a biocompatible poly(lactic-co-glycolic acid)-b-polyethyleneglycol platform. Using mouse models of cancer, the NPs efficiently accumulated in tumours, where the Pd-NP activated different model prodrugs. Longitudinal studies confirmed that prodrug activation by Pd-NP inhibits tumour growth, extends survival in tumour-bearing mice and mitigates toxicity compared to standard doxorubicin formulations. Thus, here we demonstrate safe and efficacious in vivo catalytic activity of a Pd compound in mammals.


Real-time 3D ultrasound based motion tracking for the treatment of mobile organs with MR-guided high-intensity focused ultrasound.
Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatments of mobile organs require locking the HIFU beam on the targeted tissue to maximise heating efficiency. We propose to use a standalone 3 D ultrasound (US)-based motion correction technique using the HIFU transducer in pulse-echo mode. Validation of the method was performed in vitro and in vivo in the liver of pig under MR-thermometry. 3 D-motion estimation was implemented using ultrasonic speckle-tracking between consecutive acquisitions. Displacement was estimated along four sub-apertures of the HIFU transducer by computing the normalised cross-correlation of backscattered signals followed by a triangulation algorithm. The HIFU beam was steered accordingly and energy was delivered under real-time MR-thermometry (using the proton resonance frequency shift method with online motion compensation and correction of associated susceptibility artefacts). An MR-navigator echo was used to assess the quality of the US-based motion correction. Displacement estimations from US measurements were in good agreement with 1 D MR-navigator echo readings. In vitro, the maximum temperature increase was improved by 37% as compared to experiments performed without motion correction and temperature distribution remained much more focussed. Similar results were reported in vivo, with an increase of 35% on the maximum temperature using this US-based HIFU target locking. This standalone 3D US-based motion correction technique is robust and allows maintaining the HIFU focal spot in the presence of motion without adding any burden or complexity to MR thermal imaging. In vitro and in vivo results showed about 35% improvement in heating efficiency when focus position was locked on the target using the proposed technique.


Long-term functional prognosis of posterior injuries in high-energy pelvic disruption.
This study sought to identify the long-term functional results of various posterior pelvic lesions and to determine whether such injuries benefit from exact reduction. Consecutive cohort of patients admitted for pelvic disruption between 1980 and 1990. University hospital. Eighty-eight pelvic fractures in eighty-eight patients were classified according to the instability and anatomy of the posterior injury. Simple fractures of the pubic rami, minimally displaced fractures with pubic diastasis of less than 2.5 centimeters, and fractures without other pelvic lesions (type B1 lesions, stage 1 in the Tile classification) were all excluded. Patients with sequelae of associated lesions that could render functional evaluation difficult were also excluded. The initial status of the patient and the type of fracture determined the treatment. In the anteroposterior compression injuries group, an external fixator using the double-frame Hoffmann device was applied in twenty-eight cases to reduce a large external horizontal displacement, either immediately to control bleeding or later as definitive treatment when anterior internal fixation was not possible. Anterior internal fixation with a plate was used six times to repair a symphyseal disruption. In vertical shear injuries, tibial skeletal traction was used for six weeks as an attempt to stabilize vertical instability. In ten patients, traction alone was used. In other cases, traction was used in conjunction with an external fixator or internal pubic fixation. In impacted lateral compression injuries, simple bed rest for six weeks was used in cases of stable lesions. Skeletal traction was applied in ten patients of this group because of a potential vertical instability, particularly in cases with a comminuted sacral lesion. Anatomic diagnosis and evaluation of the reduction were made using anteroposterior, inlet, and outlet radiographs of the pelvic ring. To assess reduction, vertical, anteroposterior, and rotatory displacement was measured. Functional results were qualified based on the injury pattern and the quality of the final reduction and were then quantified according to the grading proposed by Majeed. Functional results varied according to injury anatomy, with fractures of the iliac wing and sacroiliac (SI) fracture-dislocations having the best prognosis. The quality of reduction did not affect the functional results. Conservative methods such as skeletal traction and external fixation generally gave satisfactory functional results. Conversely, however, pure SI lesions were associated with poor functional results, especially if reduction was not exact. This study shows that when the posterior injury is a fracture of the iliac wing or a mixed fracture with SI propagation, a long-term satisfactory functional result can be obtained without an exact reduction even in cases of vertical instability. Simple methods are usually sufficient, and it seems unnecessary to propose more aggressive treatment. It is important, however, to recognize that SI fracture-dislocations (17 percent in this series) seem to be quite different from pure SI disruptions in terms of persistent pain. Moreover, it appears that exact reduction of pure SI lesions is critical for good functional results, something that is difficult to obtain with conservative procedures. Sacral fractures represent a special problem for the surgeon because of the frequency of fair results in which neurologic lesions whose pathophysiology is poorly known seem to be responsible.


Visualization and bibliometric analysis of 3D printing in cartilage regeneration.
The self-repair ability of cartilage defects is limited, and 3D printing technology provides hope for the repair and regeneration of cartilage defects. Although 3D printing technology and cartilage repair and regeneration have been studied for decades, there are still few articles specifically describing the relationship between 3D printing and cartilage defect repair and regeneration, and a bibliometric analysis has not been completed. To supplement, sort out and summarize the content in related fields, we analyzed the research status of 3D printing technology and cartilage repair and regeneration from 2002 to 2022. According to the set search strategy, the Web of Science Core Collection was used as the data source, and the literature search was completed on December 6, 2022. CiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published literature. Based on the analysis results, we focus on the occurrence and development of this field of combined medical and engineering research. Moreover, the current advantages and limitations of this field as well as future development prospects are discussed in depth. It will help to shape researchers' understanding of 3D printing and cartilage repair and regeneration, inspire researchers' research ideas, guide research directions, and promote related research results to clinical application.


Atorvastatin treatment in the short term: does it induce renoprotection or vasculoprotection in renal transplantation?
Proteinuria and dyslipidemia are nonimmune risk factors implicated in the deterioration of kidney function and associated with an increased risk of accelerated atherogenesis. Statin therapy, used for cholesterol reduction, has shown a renoprotective effect in animal models, particularly in cases of proteinuria. This may occur through lipid-independent mechanisms, such as improved endothelial dysfunction/vascular biology, reduced inflammatory cytokine production (transforming growth factor-beta 1 [TGF-beta1]), and regulation of fibrogenic responses. We studied mechanisms of action of agents, such as statins, to change proteinuria, inflammatory parameters, and TGF-beta1 plasma levels in relation to vascular tone. Fifty-six kidney transplant recipients (30 men and 26 women of overall mean age 54 +/- 13 years) were treated posttransplantation with atorvastatin (10 mg/d) for 12 weeks without renin-angiotensin-system blockade drugs. Inflammatory variables, biochemical parameters, lipid profile, renal function, and TGF-beta1 levels were determined at baseline and at 3 months. Vascular stiffness was evaluated using pulse wave velocity (PWV). Baseline TGF-beta1 plasma levels were higher among transplant recipients than healthy controls, namely 8.12 ng/mL (range, 5.82-13.12) to 2.55 (range, 1.78- 4.35) (P < .01). Furthermore, the levels remained higher after the treatment with atorvastatin, namely, 7.59 (range, 4.97-12.35) to 2.55 (range, 1.78-4.35) ng/mL (P < .01). Atorvastatin treatment significantly decreased total cholesterol as well as low-density lipoprotein cholesterol plasma levels, but did not modify mean blood pressure (MBP), proteinuria, creatinine clearance, or inflammatory factors. Reduction in TGF-beta1 plasma levels was statistically significant among patients with PWV >9.75 (m/s) (pathology reference value) namely, from 10.7 ng/mL (range, 7.02-13.98) to 6.7 (range, 3.96-11.94) (P = .038). Among older patients, atorvastatin significantly decrease TGF-beta1 plasma levels: from 9.5 ng/mL (range, 6.45-14.44) to 5.65 (range, 3.63-9.48; P < .05). The decreased TGF-beta1 was not related to changes in lipid profiles. Atorvastatin (10 mg/d) improved the lipid profile and moreover among older patients with worse PWV (>9.75 m/s), TGF-beta1 levels were significantly reduced. Our results suggested that statins displayed potent actions distinct from their hypolipidemic effects.


Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.
The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network.


Friction and impact surfaces: are they lead-based paint hazards?
Professionals who identify residential lead-based paint hazards and develop lead hazard control plans are instructed to assess painted friction and impact surfaces in homes as potentially active sources of dust lead, a known exposure vector for young children. However, empirical tests of the importance of these surfaces had not been conducted. Using data collected as part of a 1998 three-community study of the Housing and Urban Development Lead Risk Assessment protocols, this article explores how much rubbing or binding on friction and impact surfaces on windows and doors influence dust lead levels on windowsills and floors, while taking into account paint condition on these surfaces and other sources of lead. The analyses included windowsill dust wipe samples from 611 rooms in 182 homes and 782 floor dust wipe samples collected in 209 rooms from 104 homes. The study found that when the paint on windows is intact but the window is rubbing or binding, the dust lead levels on the windowsills are significantly higher than on windows with intact paint without rubbing or binding, after controlling for other lead sources. Windowsill dust lead on a window with intact lead-based paint at 1 mg/cm(2) and no rubbing/binding would be 27% lower than on a window with nonintact paint, rubbing/binding surfaces, or both of these conditions. An independent effect of rubbing/binding of doors on floor dust lead loadings was not observed. These findings support federal regulations calling for lead risk assessors to check the friction/impact surfaces at windows when dust lead samples taken below them are elevated, but these analyses did not offer support for taking extra observations of friction/impact surfaces around doors.