Epidemiologic trend of mobile spine and sacrum chordoma: A National population-based study.
Chordoma is a rare sarcoma of the axial skeleton. The incidence of this tumor is different between races. To understand the epidemiologic characteristic and due to rarity of this pathology, large number of cases should be evaluated through national data registries. All pathologically confirmed cases of chordoma were derived from the Iran National Cancer Registry. Descriptive analysis was performed to extract age-standardized and age-specific incidence rates. Data regarding tumor location and chordoma subtypes were derived and analyzed. One hundred twenty-two cases of chordoma including 80 male and 42 female were identified. One hundred seven cases of nonotherwise specified chordoma, 14 chondroid chordoma, and one dedifferentiated chordoma were detected. The age-standardized incidence rate (ASIR) of chordoma was 0.28. Chordoma of the sacrum composed 67.2% of cases. The mean survival time was 4.5 years. Epidemiology characteristic of chordoma in Iran is similar to other studies; however, the total ASIR was lower and the incidence in sacrum is nearly twice respect to the mobile spine. While men affected by sacral chordoma in relatively older age, the female patients had higher mean age in case of mobile spine involvement. The survival rate of chordoma is significantly lower in comparison with other studies.


Transcriptional regulation of the human pregnane-X receptor.
This review addresses the general structure and function of nuclear receptors and places specific emphasis on their role in xenosensing, resulting in the activation of a battery of genes mediating drug metabolism, conjugation, and transport. The pregnane-X receptor is a nuclear receptor that functions to control a battery of genes predominantly involved in drug metabolism and we place emphasis on how this important cellular mediator is transcriptionally activated. We have identified both positive and negative regulatory elements in the PXR promoter, the balance of which dictates the steady state expression of the PXR gene.


Molecular detection of spotted fever group rickettsiae associated with ixodid ticks in Egypt.
Tick-borne diseases comprise a complex epidemiological and ecological network that connects the vectors, pathogens, and a group of host species. The aim of this study was to identify bacteria from the genus Rickettsia associated with ixodid ticks infesting camels and cows in Egypt. Ticks were collected from 6 different localities: Qina, Giza, Qalet El Nakhl, New Valley, El Arish, and Minufia, from July to October 2008. Species were identified using PCR, followed by sequencing. The gltA and rOmpA genes were used for the initial detection of Rickettsia spp. Further characterization of positive samples utilized primers targeting rOmpB, sca4, and intergenic spacers (mppA-purC, dksA-xerC, and rpmE-tRNA(fMet)). Cows were infested with Hyalomma anatolicum excavatum and Boophilus annulatus. Camels were infested with Hyalomma dromedarii, H. impeltatum, and H. marginatum marginatum. Approximately 57.1% of H. dromedarii ticks collected from Qalet El Nakhl were infected with Rickettsia africae, exhibiting 99.1-100% identity to reference strains. Within H. impeltatum, 26.7% and 73.3% of ticks from El Arish were infected with R. africae and R. aeschlimannii, with 98.3-100% and 97.9-100% identity, respectively. Furthermore, 33.3% of H. marginatum marginatum ticks in Qalet El Nakhl were infected with the same two species as H. impeltatum, demonstrating 99.1-100% and 99.3-100% identity, respectively. By comparing percent identities and phylogenetic relationships, R. africae is identified for the first time in Egypt, in addition to R. aeschlimannii, which exhibits 100% identity with the Stavropol strain in GenBank. In conclusion, the obtained data underscore the medical and veterinary importance of tick-borne rickettsioses, which necessitate further investigation by authorities in Egypt. Moreover, additional characterization of these rickettsial isolates should be performed to designate their strains, using a polyphasic strategy combining genotypic and phenotypic tests, to facilitate their deposition in the rickettsial collection of the WHO and/or ATCC.


Prostate cancer screening: current status and future perspectives.
With the publication of the long-term results of two randomized screening trials and updates to screening guidelines from many organizations, the past 2 years have been eventful in the field of prostate cancer screening. Both the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial--which failed to identify a benefit of screening in a community setting--and the European Randomized Study of Screening for Prostate Cancer--which showed a modest benefit to screening in a clinical trial setting--have sought to address the role of screening in reducing mortality from prostate cancer. Epidemiologic evidence supports the role of PSA screening in the stage and grade migration of prostate cancer, but to date the evidence for its role in changing mortality patterns is more equivocal. As a result, little support exists at present among urologic and cancer prevention organizations for population-based PSA screening. Particularly in the USA, where PSA screening has been relatively widespread, reductions in prostate-cancer-specific mortality are likely to be in part related to improvements in treatment, rather than solely to PSA screening. The substantial risk of overdiagnosis and overtreatment of latent prostate cancer means that methods to increase the specificity of prostate cancer screening, and particularly its ability to identify high-risk disease, are essential. Strategies such as the use of 5alpha-reductase inhibitors in high-risk patients, and the continued development of urinary and genetic markers hold promise in this regard.


Postoperative pain management techniques in hip and knee arthroplasty.
Adequate control of postoperative pain following hip and knee arthroplasty can be a challenging task fraught with potential complications. Postoperative pain is perceived by the patient via a complex network and a multitude of molecular messengers in both the peripheral and central nervous systems. This allows the physician to modulate pain via an array of medications that act on different sites within the body. Using both contemporary and traditional pain modulators, the delivery and timing of these medications can affect postoperative pain and, ultimately, rehabilitation of the arthroplasty patient. Current techniques for controlling pain use both multimodal and preemptive analgesia to improve the outcome of the surgery while minimizing the potential adverse effects of the medications given.


Recent experience with trazodone.
Trazodone is an atypical antidepressant with additional anxiolytic effects. Recent European experience with trazodone is reviewed with respect to antidepressant efficacy, side effects (particularly anticholinergic), anxiolytic actions, cardiotoxicity, overdosage, and use in the elderly. From the data presented in this paper it is concluded that trazodone is effective both as an antidepressant and as an anxiolytic agent, with few side effects and low cardiotoxicity. It is safer than tricyclic antidepressant agents in overdosage and better tolerated in the elderly patient.


Role of primary bacterial contamination of a pulmonary homograft for Ross operation: report of a case and review of the literature.
In a 43-year-old female, Ross operation was performed with annular reinforcement of the autograft and a cryo-fixed homograft that proved to be contaminated with enterobacter cloacae and klebsiella pneumoniae at the time of operation. Clinical course was unremarkable, perhaps due to effective antibiotic prophylaxis and treatment. In the literature, little is known about intraoperative bacterial contamination and early endocarditis. The authors report what they believe is the second reported case. Particular resistibilities of homograft and autograft might make early endocarditis unlikely.


Development of ultrasound bioprobe for biological imaging.
We report the development of an ultrasound bioprobe for in vitro molecular imaging. In this method, the phase of the scattered ultrasound wave is mapped to provide in vitro and intracellular imaging with nanometer-scale resolution under physiological conditions. We demonstrated the technique by successfully imaging a magnetic core in silica core shells and the stiffness image of intracellular fibers in endothelial cells that were stimulated with thrombin. The findings demonstrate a significant advancement in high-resolution ultrasound imaging of biological systems with acoustics under physiological conditions. These will open up various applications in biomedical and molecular imaging with subsurface resolution down to the nanometer scale.


Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways.
Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation.


The appropriateness of use of percutaneous transluminal coronary angioplasty in New York State.
To determine the appropriateness of use of percutaneous transluminal coronary angioplasty (PTCA) in New York State. Retrospective randomized medical record. Fifteen randomly selected hospitals in New York State that provide PTCA. Random sample of 1306 patients undergoing PTCA in New York State in 1990. Percentage of patients who underwent PTCA for indications rated appropriate, uncertain, and inappropriate. The majority of patients received PTCA for chronic stable angina, unstable angina, and in the post-myocardial infarction period (up to 3 weeks). Fifty-eight percent of PTCAs were rated appropriate; 38%, uncertain; and 4%, inappropriate. The inappropriate rate varied by hospital from 1% to 9% (P = .12); the uncertain rate, from 26% to 50% (P = .02); and the combined inappropriate and uncertain rate, from 29% to 57% (P < .001). There was no difference in appropriateness when the institutions were grouped by volume (fewer than 300 procedures annually or at least 300 procedures annually), location (upstate vs downstate), or by teaching status. Few PTCAs were performed for inappropriate indications in New York State. However, the large number of procedures performed for indications that were rated uncertain as to their net benefit requires further study and justification at both clinical and policy levels.


A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.
Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine --> phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.


Gender differences of the improvement in balance control based on the real-time visual feedback system with smart wearable devices.
The body maintains stability by integrating inputs from the central nervous system of vision, hearing, proprioception, and multiple senses. With the development of smart wearable devices, smart wearable devices can provide real-time center of pressure position-assisted balance control, which is beneficial to maintain physical balance. Forty healthy college students (20 male, 20 female) participated in this study, and the posture balance actions of left-leg stance non-visual feedback, left-leg stance visual feedback, right-leg stance non-visual feedback, and right-leg stance visual feedback were performed. Visual feedback provided smart insoles matching Podoon APP on a tablet computer with the COP position displayed by a dot as real-time visual feedback. The experimental results show that the displacement, velocity, radius, and area of the COP decreased significantly in the left-leg stance visual feedback/ right-leg stance visual feedback, the test compared the parameters in the left-leg stance non-visual feedback/right-leg stance nonvisual feedback (P < 0.05). Providing visual feedback through intelligent insoles can reduce the movement of the center of mass and maintain physical stability for healthy young people of different genders. In the one leg visual/non-visual in standing, the COP maximum anteroposterior displacement, COP anteroposterior velocity, COP radius, and COP area in women are significantly smaller than in men (P < 0.05). Women have better real-time balance control ability than men with smart insoles. The simple intelligent wearable assisted devices can immediately increase the control ability in static stance of men and women, and women have better real-time balance control ability than men.


Retroperitoneal masses: different clinical scenarios.
We present two cases of retroperitoneal masses with different presentations and outcomes. The first case was a 22 years old primigravida lady who underwent emergency caesarean section for preterm premature rupture of membranes with breach. On the operating table, a large retroperitoneal mass was identified and the biopsy confirmed Burkitt's lymphoma. Post operative chemotherapy did not have a favourable result and the patient had a fatal outcome. The other case was a 15 years old boy who had a progressively increasing retroperitoneal mass. Exploratory laparotomy revealed a hard, fixed, unresectable tumour extending into the mesentery of the small gut, biopsies were taken which showed tuberculosis. Post operative antituberculosis treatment had a marked response and the tumour disappeared after 6 months.


[Risk factors for early miscarriage among intrauterine singleton pregnancies after treatment with in vitro fertilization/intracytoplasmic sperm injection].
To investigate the risk factors associated with early miscarriage among intrauterine singleton pregnancies after treatment with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A retrospective case-control study was performed on all singleton pregnancies underwent IVF/ICSI from January, 2013 to May, 2014, in Xiangya Hospital. Ninety-six early miscarriage patients served as a case group and 593 pregnancies with live birth served as a control group. We analyzed factors for early miscarriage after IVF/ICSI in two groups. Multivariate logistic regression analysis demonstrated that the women age, miscarriage history, and sperm DAN fragmentation index (DFI) were the risk factors for early miscarriage (P<0.05). Miscarriage after treatment with IVF/ICSI is affected by multiple factors. Women at elder age (>30 years old), women with a history of miscarriage or men with higher sperm DFI (≥15%) are the risk.


Trimethylamine as precursor to secondary organic aerosol formation via nitrate radical reaction in the atmosphere.
Amines in fine particulate matter have been detected and quantified during ambient studies of winter inversions in Logan, UT, using aerosol mass spectrometry. Amine-related compounds account for 0.5-6 microg m(-3) of fine particulate mass during some wintertime periods. The amine contributions sometimes show a clear diurnal pattern, reaching peak concentrations during the middle of the nightwhile decreasing during the morning and afternoon. Smog chamber reactions show that the reaction of tertiary amines with nitrate radical can account for this behavior in the atmosphere. The lower bound reaction rate of trimethylamine and nitrate radical is estimated at 4.4 x 10(-16) cm3/molecules/s with a conversion rate to the aerosol phase of approximately 65%. This suggests that amines could be a contributor to secondary organic aerosol formation in areas where nitrate radical is a significant player in oxidation chemistry.


lncRNASNP2: an updated database of functional SNPs and mutations in human and mouse lncRNAs.
Long non-coding RNAs (lncRNAs) are emerging as important regulators in different biological processes through various ways. Because the related data, especially mutations in cancers, increased sharply, we updated the lncRNASNP to version 2 (http://bioinfo.life.hust.edu.cn/lncRNASNP2). lncRNASNP2 provides comprehensive information of SNPs and mutations in lncRNAs, as well as their impacts on lncRNA structure and function. lncRNASNP2 contains 7260238 SNPs on 141353 human lncRNA transcripts and 3921448 SNPs on 117405 mouse lncRNA transcripts. Besides the SNP information in the first version, the following new features were developed to improve the lncRNASNP2. (i) noncoding variants from COSMIC cancer data (859534) in lncRNAs and their effects on lncRNA structure and function; (ii) TCGA cancer mutations (315234) in lncRNAs and their impacts; (iii) lncRNA expression profiling of 20 cancer types in both tumor and its adjacent samples; (iv) expanded lncRNA-associated diseases; (v) optimized the results about lncRNAs structure change induced by variants; (vi) reduced false positives in miRNA and lncRNA interaction results. Furthermore, we developed online tools for users to analyze new variants in lncRNA. We aim to maintain the lncRNASNP as a useful resource for lncRNAs and their variants.


Training volunteers as conversation partners using "Supported Conversation for Adults with Aphasia" (SCA): a controlled trial.
This article reports the development and evaluation of a new intervention termed "Supported Conversation for Adults with Aphasia" (SCA). The approach is based on the idea that the inherent competence of people with aphasia can be revealed through the skill of a conversation partner. The intervention approach was developed at a community-based aphasia center where volunteers interact with individuals with chronic aphasia and their families. The experimental study was designed to test whether training improves the conversational skills of volunteers, and, if so, whether the improvements affect the communication of their conversation partners with aphasia. Twenty volunteers received SCA training, and 20 control volunteers were merely exposed to people with aphasia. Comparisons between the groups' scores on a Measure of Supported Conversation for Adults with Aphasia provide support for the efficacy of SCA. Trained volunteers scored significantly higher than untrained volunteers on ratings of acknowledging competence [F(1, 36) = 19. 1, p < .001] and revealing competence [F(1, 36) = 159.0, p < .001] of their partners with aphasia. The training also produced a positive change in ratings of social [F(1, 36) = 5.7, p < .023] and message exchange skills [F(1, 36) = 17.6, p < .001 ] of individuals with aphasia, even though these individuals did not participate in the training. Implications for the treatment of aphasia and an argument for a social model of intervention are discussed.


Forum: allocation, misallocation and reallocation of health care resources. Interview by Merit Kimball.
Calling cost containment efforts to date mostly "appearance ... that is not what the game is about...," a Harvard medical economist sets forth his views about how America has spent--and should be spending--its health care dollars. He suggests directions the country might take toward establishment of a national health insurance policy administered by the states.


Effect of a mindfulness programme training on mental toughness and psychological well-being of female athletes.
Research has shown that mindfulness in athletes is associated with positive outcomes. We therefore assessed the effect of mindfulness training on increasing mental toughness (MT) and psychological well-being (PWB). This was a parallel-group, pre-and post-test, randomised controlled pilot trial. Forty-five female athletes from Iranian universities in Tehran were randomly assigned into experimental (n = 23) and control groups (n = 22). Forty-two completed the trial. The mindfulness training group received the Mindfulness-Acceptance-Commitment programme for 7 weeks. All subjects completed the Mindfulness Inventory for Sport (MIS), Sports Mental Toughness Questionnaire and PWB Scale. Data were analysed using mixed analysis of variance. Mindfulness training increased mindfulness in the experimental group (p < 0.01). In turn, increased mindfulness led to increased MT and PWB at 2-month follow-up (p < 0.05). Given that mindfulness training may increase the MT and PWB of athletes, these techniques should be considered for inclusion in sports coaching.


Characterization of synovial fluid fibronectin from patients with rheumatic inflammatory diseases and healthy subjects.
Synovial fluid fibronectin from normal subjects and from patients who have rheumatic inflammatory diseases has been studied and compared with plasma fibronectin. The average fibronectin concentration in synovial fluids from normal subjects was 172 +/- 69 micrograms/ml; it was 721 +/- 315 and 556 +/- 349 micrograms/ml in synovial fluids from patients with rheumatoid arthritis and osteoarthritis, respectively. This is the first report on fibronectin concentrations in normal synovial fluids. Synovial fluid fibronectin from healthy subjects and patients with rheumatoid arthritis or osteoarthritis showed a molecular weight identical to that of plasma fibronectin. All normal and pathologic synovial fluid fibronectins showed a remarkably lower electrophoretic mobility compared with that of plasma fibronectin, when separated according to net molecular charge on agarose gel. Peptides from thermolysin digests of fibronectin from plasma and synovial fluid, when compared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed distinct differences. These data demonstrate that synovial fluid fibronectin represents a molecular form which is structurally different from that of plasma fibronectin. This suggests that synovial fluid fibronectin is locally synthesized, possibly by a cell type which differs from that responsible for the production of the plasmatic fibronectin pool.


Stereospecific conversion of 1-aminocyclopropanecarboxylic Acid to ethylene by plant tissues : conversion of stereoisomers of 1-amino-2-ethylcyclopropanecarboxylic Acid to 1-butene.
Inasmuch as the molecule of 1-aminocyclopropanecarboxylic acid (ACC) possesses reflective symmetry but lacks rotational symmetry, the two chemically alike methylene groups can be distinguished by a stereospecific enzyme. To determine whether ACC conversion to ethylene by plant tissues proceeds in a stereospecific fashion, the four stereoisomers of 1-amino-2-ethylcyclopropanecarboxylic acid (AEC) were administered to postclimacteric apple (Malus sylvestris Mill., var. Golden Delicious), excised preclimacteric cantaloupe (Cucumis melo L., var. reticulatis Naud cv. PMR-45), and etiolated mung bean (Vigna radiata L., Wilczek, var. Berken) hypocotyls. In each case (1R,2S)-AEC was the preferred substrate yielding 1-butene. In contrast, all AEC isomers were converted equally well to butene by chemical oxidation using NaOCl. Both ACC and AEC appear to be substrates for the same enzyme since both reactions are inhibited in parallel by N(2) or Co(2+), both reactions are induced in parallel by excision, and when both substrates are present simultaneously each will act as an inhibitor with respect to the other. The aforementioned observations indicate that ACC is stereospecifically converted to ethylene. For AEC to be the most active precursor of 1-butene, the ethyl substituent should be trans to the carboxyl group and the pro-(S) methylene group should be unsubstituted. This observation leads to the suggestion that the enzyme interacts with amino, carboxyl, and pro-(S) methylene groups, a configuration corresponding to a l-amino acid. This view is consistent with the observation that the l-forms of alanine and methionine inhibit the conversion of ACC to ethylene more than the corresponding d-amino acids in the mung bean hypocotyl system.


Effects of different concentrations of atropine on controlling myopia in myopic children.
Although 1% atropine effectively slows myopia progression, it is associated with adverse effects, including photophobia, blurred near vision, and poor compliance. We investigated whether lower doses of atropine would control myopia progression. One hundred and eighty-six children, from 6 to 13 years of age, were treated each night with different concentrations of atropine eye drops or a control treatment for up to 2 years. The mean myopic progression in each of the groups was 0.04 +/-0.63 diopter per year (D/Y) in the 0.5% atropine group, 0.45+/-0.55 D/Y in the 0.25% atropine group, and 0.47+/-0.91 D/Y in the 0.1% atropine group. All atropine groups showed significantly less myopic progression than the control group (1.06+/-0.61 D/Y) (p<0.01). Our study also showed that 61% of students in the 0.5% atropine group, 49% in the 0.25% atropine group and 42% in the 0.1% atropine group had no myopic progression. However, 4% of children in the 0.5% atropine group, 17% in the 0.25% atropine group, and 33% in the 0.1% atropine group still had fast myopic progression (>-1.0 D/Y). In contrast, only 8% of the control group showed no myopic progression and 44% had fast myopic progression. These results suggest that all three concentrations of atropine had significant effects on controlling myopia; however, treatment with 0.5% atropine was the most effective.


Eating habits, health attitudes and obesity indices among medical students in northern Greece.
Medical students represent not only the final but also the most crucial opportunity for education in the field of healthy lifestyles and nutritional habits. Eating habits and obesity indices among medical students in southern Greece were described almost a decade ago. However, there is a lack of current, relevant data concerning students living in northern Greece. The purpose of the present study was to evaluate the body mass index distribution and nutritional and health-related behavior among medical students in northern Greece. The participants, 187 males (21.5 ± 1.9 years) and 203 females (21.3 ± 2.2 years), filled out a self-report questionnaire. Height and weight measurements were obtained. Dietary practices of fast food consumption (more frequent for males) and regular consumption of fruits and vegetables (more frequent for females) were reported. Females seemed to adopt different practices than males when trying to lose weight and were significantly better informed about the nutrient value of the food consumed. Although the prevalence of overweight (males: 32.1%, females: 8.4%) and obesity (males: 5.9%, females: 1.5%) in the present sample is lower compared to previous data, it remains high according to what would be health promoting. The above findings suggest a need for further improvement in strategies promoting healthier nutrition habits.


[Preparation of macrocycle antibiotic chiral stationary phases by wrapping with a net in high performance liquid chromatography].
Vancomycin and teicoplanin are glycopeptide macrocyclic antibiotics with three-dimensional ring structures and multiple chiral centers. They are commonly used chiral recognition materials in enantioseparation by high-performance liquid chromatography. In this study, six chiral stationary phases wrapped with a net on silica gels were prepared by interfacial polymerization using vancomycin and teicoplanin as chiral selectors, piperazine as a monomer, 4,4'-diphenylmethane diisocyanate (MDI), 1,6-hexamethylene diisocyanate (HDI), and 2,4-toluene diisocyanate (TDI) as crosslinker. The fabricated chiral columns were used for enantioseparations. Compared to the crosslinked and commercial columns composed of vancomycin and teicoplanin, the columns wrapped with a net exhibited complementarity for the optical resolutions.


Prospective Randomized Comparison of Locked Plates Versus Nonlocked Plates for the Treatment of High-Energy Pilon Fractures.
To compare the radiographic and functional outcome of patients with high-energy pilon fractures treated with locked versus nonlocked plates. Randomized prospective trial. Academic level 1 trauma center. Between December 2006 and December 2008, 60 consecutive patients with 62 AO/OTA type A, B, and C tibial pilon fractures were enrolled in the study. Thirty-two of the fractures were treated using locked plates and 29 were treated with nonlocked plates. Follow-up data were available for 33 of the 60 patients. Treatment with locked versus nonlocked plates. Short Musculoskeletal Function Assessment (SMFA) questionnaire and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHS). Radiographic measurements on anteroposterior and lateral views for the quality of reduction and maintenance of alignment immediately postoperatively compared with the latest follow-up. There were no significant differences in the mechanism or injury pattern, average age of the patients, ratio of males to females, tourniquet time, operative time, interval to surgery, AHS, or SMFA scores. One of 15 fractures in the locked plate group lost reduction at the latest follow-up compared with 3 of 19 fractures in the nonlocked group. In this study, there seems to be no difference between the 2 constructs. Thus, one must question the routine use of locked plates in the treatment of high-energy pilon fractures. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity.
This study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals. By post-AMI day 21, left ventricular ejection fraction (LVEF) was lowest in untreated AMI animals, significantly higher in SC than in AMI-Tac group (all p<0.003). Infarct areas at basal, middle, and apical levels, numbers of CD14+ and iNOS+ cells in infarct area (IA) and peri-IA, and protein expression of CD14, CD68, and Ly6g from circulating inflammatory cells showed an opposite pattern compared with that of LVEF in all groups (all p<0.005). Protein expressions of MCP-1, MIP-1, TNF-α, NF-κB, iNOS, and IL-12 in IA and peri-IA exhibited an identical pattern compared to that of CD14, CD68, and Ly6g from circulating inflammatory cells (all p<0.01). Expressions of myocardial damage biomarkers in IA and peri-IA [γ-H2AX, β-myosin heavy chain (MHC), Smad3, TGF-β] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, α-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001). Innate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment.


Blood pressure reduction with ECT response.
A group of 48 male inpatients who responded to electroconvulsive therapy for major depression showed decreases in resting blood pressure along the course of treatment. Decreases occurred in both systolic (mean +/- SD = 8.0 +/- 17.3 mm Hg, p = .0025) and diastolic (7.4 +/- 13.2 mm Hg, p = .00030) pressures. Systolic pressure decreased by at least 20 mm Hg in 15 patients. These findings are consistent with reports that depressives show elevated plasma catecholamine levels, and that, with response to tricyclic antidepressants, their blood pressures decrease. Depression-associated blood pressure elevation might contribute to the excessive cardiac mortality of depressives; conversely, antidepressant treatment might control hypertension in some depressives.


A nano-needle/microtubule composite gliding on a kinesin-coated surface for target molecule transport.
An alternative method of micro/nano-transport has been achieved by using motor proteins. Microtubules on a kinesin-coated surface have potential to act as a nano-transport system. When microtubules are used as carriers, either cargo or cargo linkers are attached on the microtubule surface. Such cargo attachments can significantly affect kinesin motion. To deal with the difficulty caused by molecular attachment to the microtubule surface, the cargo loading and transport mechanism should be separated. In this work, we propose to use micromachined needles as cargo carriers which then can be transported on microtubules. Because of the separation of needle functionalization and transport mechanism, functionalization of the needles can proceed without any effect on the microtubule structure, significantly increasing the possible types of cargo. We have fabricated silicon needles in mass numbers using a simple and effective method and have shown that the microtubule-needle composites are transported without affecting the kinesin activity.


Gastric metaplasia and small bowel ulcerogenesis in a case of ulcerative jejunitis not related to celiac disease.
The possible relationship between gastric metaplasia and ulcerative lesions in an unusual case of ulcerative jejunitis not related to celiac disease and with extensive gastric metaplasia is discussed. Previous studies have described gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some authors maintain that acid secretion in metaplastic mucosa could represent a pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the absence of functional evidence, we could provide data, in a case of ulcerative jejunitis, about morphologic signs of acid secretion in gastric metaplastic epithelium using an antibody against HMFG-1, a good marker of acid-secreting fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and these finding are suggestive of local acid secretion.


Utilization of a Best Practice Alert (BPA) at Point-of-Care for Recruitment into a US-Based Autism Research Study.
Provider referral is one of the most influential factors in research recruitment. To ease referral burden on providers, we adapted the Best Practice Alert (BPA) in the EPIC Electronic Health Record and assessed its utility in recruiting pediatric patients with autism spectrum disorder for the national SPARK study. During a year-long surveillance, 1203 (64.0%) patients were Interested in SPARK and 223 enrolled. Another 754 participants not recruited via the BPA also enrolled; 35.5% of these participants completed their participation compared to 58.3% of BPA-referred participants. Results suggest that (a) a BPA can successfully engage providers in the study-referral process and (b) families who learn about research through their providers may be more engaged and effectively retained.


Familial incidence of multiple births in a colony of chimpanzees (Pan troglodytes).
This paper describes the incidence of multiple births in the Yerkes Chimpanzee colony for a period of about 63 years. Pedigrees are presented for all multiple births. They demonstrate the recurrence of twins in relatively few family lines which can be traced back to a small number of ancestors. The findings suggest that twinning is a family trait in chimpanzees and they support the hypothesis that the incidence of multiple births is genetically influenced in this colony. In addition, a relatively high level of inbreeding may have enhanced the incidence of multiple births in these family lines. Similar findings are known from human populations.


T cell receptor signals enhance susceptibility to Fas-mediated apoptosis.
Fas(CD95) and its ligand (FasL) interaction plays a pivotal role in T cell receptor (TCR)-mediated apoptosis. However, the susceptibility of T cells to Fas-mediated apoptosis is tightly regulated during immune responses, a regulation which is thought to maintain the antigen-specificity of T cell apoptosis. Here we show that TCR stimulation enhances the induction of Fas-mediated apoptosis. In addition, using a mutant T cell hybridoma with impaired FasL expression, we show that the synergy provided by TCR stimulation can be mimicked by activators of PKC but not calcium influx. This effect cannot be inhibited by actinomycin D, suggesting that TCR stimulation leads to the alteration in preexisting signaling molecules to enhance Fas-mediated apoptosis. Our results therefore provide a mechanism of how Fas-FasL interactions lead to T cell death in an antigen-specific manner via repetitive antigen stimulation.


A catalogue of selected derivatization reactions to label molecules in the subnanomolar or nanomolar range for CE and micro-HPLC with LIF detection.
Sensitivity is a major obstacle to biochemists studying complex biological mixtures. Laser-induced fluorescence (LIF) is a very sensitive method that can be used with micro-HPLC (microHPLC) or capillary electrophoresis studies and provides an effective solution to these problems. Derivatization is a very useful tool in LIF detection because it allows for the detection of many compounds and is selective, i.e., one dye will label one chemical function specifically. The major difficulty is choosing a derivatization reaction among the huge number of reactions described in the literature and making it work at a very low level of concentration. Another limitation is the use of a laser wavelength, which can excite the derivatized molecules. This article discusses selected derivatization reactions for labeling molecules in the subnanomolar or nanomolar range for CE and microHPLC. Derivatization for amines, sugars, aldehydes, carboxylic acids, thiols, diols, and nucleotides are described, and derivatization procedures are presented. In many cases, the subnanomolar and nanomolar concentration of these compounds can be detected using these chemical reactions.


In vitro cardiac function in early sepsis.
The involvement of the myocardium in the injury resulting from bacteremia has been somewhat controversial. Recently, some investigators have suggested that the transition from an early stage of sepsis, in which the cardiovascular system is stable and mortality is relatively low, to the late or preterminal stage of sepsis is a result of cardiac dysfunction. Here, however, data are presented to show that contractile defects and loss of myocardial reserve occur even early during a septic episode, i.e., at a time when cardiac output is elevated or normal. Efforts to determine the mechanism of the cardiac dysfunction are described. These entail studies of whole heart performance under conditions of varying the calcium availability for contraction and assessment of subcellular organelle function. The data indicate that calcium dyshomeostasis may at least partially contribute to the cardiac dysfunction of sepsis. The in vivo adequacy of cardiac function probably results from the capacity of the myocardium in early sepsis to respond to catecholamine support of chronotropy and inotropy.


[Longitudinal decline of forced expiratory volume in one second in non-smoking Japanese women].
We prospectively studied 1,696 clinically healthy non-smoking women to assess the influence of aging on longitudinal decline in forced expiratory volume in one second (FEV10). All the subjects took an annually medical examination involving a pulmonary function test from 1995 to 2001. The mean value of annual decrease in FEV10 (slope) was 19.6 mL/year. Multiple regression analysis revealed that initial age, height, and FEV10 were significant parameters determining the slope. This study clearly showed the aging-related longitudinal decline in pulmonary function in non-smoking Japanese women.


Isotypic analysis of antibody response to a food antigen in inflammatory bowel disease.
We studied the class-specific antibody response to the cow's milk antigen beta-lactoglobulin (beta-LG) in sera from patients with ulcerative colitis and Crohn's disease. IgG and IgM to beta-LG were significantly higher in patients when compared to healthy non-atopic controls, whereas IgA values were similar, and specific IgE absent in all groups. No correlation between IgG- or IgM-containing immune complexes was found with the corresponding isotype of antibody to beta-LG; however, IgM complexes correlated with serum total IgM in ulcerative colitis. In these patients, IgG antibodies were higher in active cases, whereas IgM increased in patients without signs of disease activity. Antibody titers did not correlate with disease duration or administration of antiinflammatory drugs. This pattern of anti-beta-LG reactivity suggests that the presence of intestinal lesions may be revealed by the selective increase of some antibody isotypes to orally administered antigens. Enhanced mucosal permeability may be studied by this type of serological analysis.


Ultrasound findings in a patient with primary orbital hemangiopericytoma.
A 20-year-old white male with a left superorbital mass and significant left proptosis was referred from his primary care physician. A and B scan ultrasound examination revealed a mass in the superonasal quadrant of the left orbit that demonstrated compression, encapsulation, internal vascularity and low internal reflectivity. Diagnosis of orbital hemangiopericytoma was confirmed histologically from frozen sections taken during surgical excision of the tumor.


Effects of copper on CHO cells: cellular requirements and product quality considerations.
Recent reports highlight the impact of copper on lactate metabolism: CHO cell cultures with higher initial copper levels shift to net lactate consumption and yield lower final lactate and higher titers. These studies investigated the effects of copper on metabolite and transcript profiles, but did not measure in detail the dependences of cell culture performance and product quality on copper concentrations. To more thoroughly map these dependences, we explored the effects of various copper treatments on four recombinant CHO cell lines. In the first cell line, when extracellular copper remained above the limit of detection (LOD), cultures shifted to net lactate consumption and yielded comparable performances irrespective of the differences in copper levels; when extracellular copper dropped below LOD (∼13 nM), cultures failed to shift to net lactate consumption, and yielded significantly lower product titers. Across the four cell lines, the ability to grow and consume lactate seemed to depend on the presence of a minimum level of copper, beyond which there were no further gains in culture performance. Although this minimum cellular copper requirement could not be directly quantified, we estimated its probable range for the first cell line by applying several assumptions. Even when different copper concentrations did not affect cell culture performance, they affected product quality profiles: higher initial copper concentrations increased the basic variants in the recombinant IgG1 products. Therefore, in optimizing chemically defined media, it is important to select a copper concentration that is adequate and achieves desired product quality attributes.


The diabetes epidemic in Sri Lanka - a growing problem.
Diabetes mellitus, which was once considered a disease of the developed world, has become a worldwide pandemic, with two thirds of the global diabetic population living in the developing countries. Local studies show a definite upward trend in the prevalence of diabetes mellitus. The earliest available study on a rural community in 1990 reported a prevalence of 2.5%. The largest-ever study on the diabetes prevalence in Sri Lanka was published in 2005. It showed a prevalence of 14.2% among males and 13.5% among females. The World Health Organisation and the International Diabetic Federation estimates and forecasts are much lower than the available local prevalence rates, and what may be predicted from the prevalence rates in South India. Further research is necessary to investigate the exact underlying mechanisms for the South Asian epidemic. Wider preventive programmes need to be urgently implemented to stem the tide.


Frostbite injury of the breast: a case report.
This paper presents an unusual case of frostbite injury to the breast area caused by faulty cryotherapy application. Cryotherapy, commonly used by patients and health professionals, relieves pain and edema after trauma and sports injuries. However, applying cold therapy is not common for surgical procedures involving soft tissue. The frostbite injury to the breast presented here occurred due to persistent use of a self-prepared ice pack following a needle aspiration biopsy. Cold exposure to soft tissue may cause frostbite. It is crucial to inform patients about proper application of cryotherapy and possible complications, particularly for the procedures in which cold therapy is not widely used.


Understanding the Emotional Intelligence Discourse on Social Media: Insights from the Analysis of Twitter.
Social networks have created an information diffusion corpus that provides users with an environment where they can express their views, form a community, and discuss topics of similar or dissimilar interests. Even though there has been an increasingly rising demand for conducting an emotional analysis of the users on social media platforms, the field of emotional intelligence (EI) has been rather slow in exploiting the enormous potential that social media can play in the research and practice of the framework. This study, thus, tried to examine the role that the microblogging platform Twitter plays in enhancing the understanding of the EI community by building on the Twitter Analytics framework of Natural Language Processing to further develop the insights of EI research and practice. An analysis was conducted on 53,361 tweets extracted using the hashtag emotional intelligence through descriptive analytics (DA), content analytics (CA), and network analytics (NA). The findings indicated that emotional intelligence tweets are used mostly by speakers, psychologists (or other medical professionals), and business organizations, among others. They use it for information dissemination, communication with stakeholders, and hiring. These tweets carry strong positive sentiments and sparse connectedness. The findings present insights into the use of social media for understanding emotional intelligence.


[Correlation between intracellular cyclic AMP level and cytotoxic sensitivity to anti-tumor-associated antigen antibody in rat fibrosarcoma cells].
We investigated the intracellular cyclic AMP (cAMP) level and cytotoxic sensitivity to anti-tumor-associated antigen (anti-TAA) antibody in transplantable rat fibrosarcoma cells with regard to each of three days following ip transplantation. The cytotoxic sensitivity of the 3-methylcholanthrene (MCA)-induced transplantable fibrosarcoma KMT-17 cells to anti-TAA antibody decreased daily after ip transplantation in syngeneic WKA/Hok rats. In contrast, the intracellular cAMP level of the tumor cells increased daily after ip transplantation, and the cAMP level of 3-day-old KMT-17 tumor cells (1.31 pmol/10(6) cells) was statistically (p less than 0.01) higher than that of 1-day-old tumor cells (1.01 pmol/10(6) cells). This phenomenon disappeared, however, after artificial infection of the tumor cells with Friend murine leukemia virus (F-MuLV). The cytotoxic sensitivity of F-MuLV-infected KMT-17 (FV-KMT-17) tumor cells to anti-TAA antibody did not decrease and no elevation of the intracellular cAMP level was observed (0.92-0.97 pmol/10(6) cells), regardless of the number of days after ip transplantation. The cytotoxic sensitivity of KMT-17 and FV-KMT-17 tumor cells to anti-TAA antibody was therefore in inverse proportion to the intracellular cAMP levels of the tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839).
Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and quality-of-life of a subset of patients with advanced non-small cell lung cancer (NSCLC). However, a large portion of the patients showed no effect to this agent. To establish a method to predict the response of NSCLC patients to gefitinib, we used a genome-wide cDNA microarray to analyze 33 biopsy samples of advanced NSCLC from patients who had been treated with an identical protocol of second to seventh line gefitinib monotherapy. We identified 51 genes whose expression differed significantly between seven responders and 10 non-responders to the drug. We selected the 12 genes that showed the most significant differences to establish a numerical scoring system (GRS, gefitinib response score), for predicting response to gefitinib treatment. The GRS system clearly separated the two groups without any overlap, and accurately predicted responses to the drug in 16 additional NSCLC cases. The system was further validated by the semi-quantitative RT-PCR, immunohistochemistry and ELISA for serological test. Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro. Our results suggested that sensitivity of a given NSCLC to gefitinib can be predicted according to expression levels of a defined set of genes that may biologically affect drug sensitivity and survival of lung cancer cells. Our scoring system might eventually lead to achievement of personalized therapy for NSCLC patients.


Role of Functional IFNL4, IFNLR1, IFNA, IFNAR2 Polymorphisms in Hepatitis B virus-related liver disease in Han Chinese population.
Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)-related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1-rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV-related liver disease by trend chi-square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5' region of the IFNL4 gene are associated with the progression of HBV-related liver disease. IFNA1- rs1831583 and IFNA2- rs649053 are associated with the development of HCC. IFNLR1- rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 -rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.


Universal divergenceless scaling between structural relaxation and caged dynamics in glass-forming systems.
On approaching the glass transition, the microscopic kinetic unit spends increasing time rattling in the cage of the first neighbors, whereas its average escape time, the structural relaxation time tau(alpha), increases from a few picoseconds up to thousands of seconds. A thorough study of the correlation between tau(alpha) and the rattling amplitude, expressed by the Debye-Waller factor, was carried out. Molecular-dynamics simulations of both a model polymer system and a binary mixture were performed by varying the temperature, the density rho, the potential and the polymer length to consider the structural relaxation as well as both the rotational and the translation diffusion. The present simulations, together with MD studies on other glassformers, evidence the scaling between the structural relaxation and the caged dynamics. An analytic model of the master curve is developed in terms of two characteristic length scales a(2) (1/2) and sigma(a(2) ) (1/2), pertaining to the distance to be covered by the kinetic unit to reach a transition state. The model does not imply tau(alpha) divergences. The comparison with the experiments supports the numerical evidence over a range of relaxation times as wide as about eighteen orders of magnitude. A comparison with other scaling and correlation procedures is presented. In particular, the density scaling of the length scales a(2) (1/2), sigma(a(2) ) (1/2) proportional to rho(-1/3) is shown to be not supported by the present simulations. The study suggests that the equilibrium and the moderately supercooled states of the glassformers possess key information on the huge slowing-down of their relaxation close to the glass transition. The latter, according to the present simulations, exhibits features consistent with the Lindemann melting criterion and the free-volume model.


[Research progress on occupational exposure and protection from acquired immunodeficiency syndrome in stomatological departments].
Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by human immunodeficiency virus (HIV). The disease is highly infectious, quickly spreads, and has a high fatality rate. Hence, it is a major concern in public health, and an important subject in the prevention and treatment of infectious diseases. The medical staff of stomatological departments, which handle the diagnosis and treatment of oral diseases, are at particularly high risk of occupational exposure to HIV/AIDS. This study summarizes the HIV/AIDS epidemic status, disease transmission routes, oral lesions in HIV/AIDS patients, occupational exposure, and occupational protection in stomatological departments.


Phase II study of a combination of cisplatin, all-trans-retinoic acid and interferon-alpha in squamous cell carcinoma: clinical results and pharmacokinetics.
Preclinical and clinical data suggest a certain antitumor efficacy for combination of retinoids, cytokines and cytotoxic compounds. Between November 1994 and October 1996, 38 patients with advanced squamous cell carcinoma were enrolled in a phase II study to investigate an association of low-dose all-trans-retinoic acid (tRA) (40 mg/m2/day, 84 days), interferon-alpha (IFN-alpha) (6.10(6) UI/day, 84 days s.c.) and cisplatin (40 mg/m2/day, day 1, 28 and 56, i.v.). A Pharmacokinetic evaluation was performed on 12 patients. The incidence of grade 3/4 hematologic toxicities was moderate (< 20%). Extra hematological toxicities were frequent but easily manageable and not life threatening. However, treatment delivery was poor since only 6 patients (16%) received full therapy. Seven objective responses were observed (21%), suggesting some degree of synergism between tRA, IFN-alpha and cisplatin. Interestingly, continuous tRA treatment in combination with IFN-alpha and cisplatin did not induce a significant decrease in plasma levels, as had been previously described. Regarding the short median response duration and the frequency of toxic events, this regimen should no longer be recommended in pretreated patients with advanced disease. However, the consistent response rate reported here may warrant further investigation in an early setting.


Effects of cocoa extract on glucometabolism, oxidative stress, and antioxidant enzymes in obese-diabetic (Ob-db) rats.
In this present study, we investigated the effects of cocoa extract containing polyphenols and methylxanthines prepared from cocoa powder on the biochemical parameters of obese-diabetic (Ob-db) rats. Obese-diabetic (Ob-db) rats were developed using a high-fat diet (49% fat, 32% carbohydrate, and 19% protein from total energy, kcal) for 3 months, followed by a low dose (35 mg/kg body weight) streptozotocin (STZ) injection. Cocoa extract (600 mg/kg body weight/day) was given to the rats for 4 weeks. The results indicated that there were no significant differences in fasting plasma glucose and insulin level after 4 weeks of cocoa extract administration. Oral glucose tolerance test revealed that cocoa supplementation in Ob-db rats significantly (p < 0.05) reduced plasma glucose at 60 and 90 min compared to unsupplemented Ob-db rats. Plasma free fatty acid and oxidative stress biomarker (8-isoprostane) were significantly (p < 0.05) reduced after cocoa supplementation. Superoxide dismutase activity was enhanced in Ob-db compared to that in nonsupplemented rats. However, no change was observed in catalase activity. The results showed that cocoa supplementation had an effect on postprandial glucose control but not for long term (4 weeks). Moreover, cocoa supplementation could reduce circulating plasma free fatty acid and 8-isoprostane and may enhance the antioxidant defense system.


[Expression of the cold receptor TRPM8 in the smooth muscles of the seminal ejaculatory ducts in rats].
By means of real-time RT-PCR and immunofluorscent staining combined with confocal microscopy we show for the first time the expression ofmRNA and protein ofthe cold/menthol-sensitive cationic channel, TRPM8, in the smooth muscle cells (SMC) from the epididimal and prostatic portions of the rat vas deferens. Expression of TRPM8 mRNA correlated with the expression ofmRNA for androgen receptor (AR): orchidectomy of the animals resulted in the enhancement of the expression of both mRNAs, which likely reflects specific for the vas deferens compensatory response to the decreasing levels of circulating androgens. TRPM8 protein in the SMC from both parts of the vas deferens primarily localized outside the plasma membrane (PM), however, in the SMC from prostatic portion we observed higher TRPM8 protein targeting specifically the endoplasmic reticulum and PM, where it can form functional cold/menthol-sensitive cationic channel capable of modulating contractile activity of the smooth muscle.


A Fluorescent Assay to Search for Inhibitors of HIV-1 Integrase Interactions with Human Ku70 Protein, and Its Application for Characterization of Oligonucleotide Inhibitors.
The search for compounds that can inhibit the interaction of certain viral proteins with their cellular partners is a promising trend in the development of antiviral drugs. We have previously shown that binding of HIV-1 integrase with human Ku70 protein is essential for viral replication. Here, we present a novel, cheap, and fast assay to search for inhibitors of these proteins' binding based on the usage of genetically encoded fluorescent tags linked to both integrase and Ku70. Using this approach, we have elucidated structure-activity relationships for a set of oligonucleotide conjugates with eosin and shown that their inhibitory activity is primarily achieved through interactions between the conjugate nucleic bases and integrase. Molecular modeling of HIV-1 integrase in complex with the conjugates suggests that they can shield E212/L213 residues in integrase, which are crucial for its efficient binding to Ku70, in a length-dependent manner. Using the developed system, we have found the 11-mer phosphorothioate bearing 3'-end eosin-Y to be the most efficient inhibitor among the tested conjugates.


Isothermal Cold Crystallization, Heat Resistance, and Tensile Performance of Polylactide/Thermoplastic Polyester Elastomer (PLA/TPEE) Blends: Effects of Annealing and Reactive Compatibilizer.
The combined influences of crystallinity and reactive compatibilizer-a multifunctional epoxide (ADR)-on morphology, tensile performance, and heat resistance of polylactide/thermoplastic polyester elastomer (PLA/TPEE) (80/20) blends were investigated. Annealing involved an isothermal cold crystallization of PLA matrix was performed to increase crystallinity of the samples. First, isothermal cold crystallization kinetics were investigated using differential scanning calorimetry measurement. It was found that the addition of ADR decreased the crystallization rate of the samples. The maximum crystallinity of the annealed samples also decreased from 40% to 34% while ADR loading increased from zero to 1.0 phr. Furthermore, influence of crystallinity on mechanical performances of the PLA/TPEE sample was researched. The heat resistance of the sample showed a significant enhancement while increasing its crystallinity. Meanwhile, the tensile ductility of the crystallized PLA/TPEE sample became very poor due to the embrittlement with increased crystallinity and the incompatibility between PLA and TPEE. However, the annealed PLA/TPEE/ADR samples with high crystallinity kept a higher tensile ductility because ADR greatly improved the interfacial compatibility. Differences in tensile fracture behaviors of the quenched and annealed PLA/TPEE samples with and without ADR were discussed in detail. At last, crystallized PLA/TPEE/ADR blends with excellent heat resistance and high tensile ductility were obtained by annealing and reactive compatibilization.


Study in China on ingestion and organ content of trace elements of importance in radiological protection.
To improve knowledge of the ingestion and organ content of calcium, cesium, iodine, potassium, strontium, thorium, and uranium that have a high priority in radiological protection, a total diet and organ content studies was conducted. The total diet study used the market basket sample method with representative sampling. For the organ content specimens of muscle, skeleton, liver, kidney, lung, and thyroid were collected during autopsies of normal, healthy adult accidental death victims. The concentration of above stated elements in the diet and organs were analyzed by nuclear and nuclear-related techniques with strict quality assurance measures. The results are presented in the paper and compared with previous national and international data and the parameters of current International Commission on Radiological Protection (ICRP) Reference Man. The study provided a new and reliable database for setting the parameters for the Chinese reference man and the reference Asian man. It also facilitated the study on biokinetics behavior of their radiation counterparts in human body and helped in the realistic assessment of their internal radiation doses.


3D Structure of fish muscle myosin filaments.
Myosin filaments isolated from goldfish (Carassius auratus) muscle under relaxing conditions and viewed in negative stain by electron microscopy have been subjected to 3D helical reconstruction to provide details of the myosin head arrangement in relaxed muscle. Previous X-ray diffraction studies of fish muscle (plaice) myosin filaments have suggested that the heads project a long way from the filament surface rather than lying down flat and that heads in a single myosin molecule tend to interact with each other rather than with heads from adjacent molecules. Evidence has also been presented that the head tilt is away from the M-band. Here we seek to confirm these conclusions using a totally independent method. By using 3D helical reconstruction of isolated myosin filaments the known perturbation of the head array in vertebrate muscles was inevitably averaged out. The 3D reconstruction was therefore compared with the X-ray model after it too had been helically averaged. The resulting images showed the same characteristic features: heads projecting out from the filament backbone to high radius and the motor domains at higher radius and further away from the M-band than the light-chain-binding neck domains (lever arms) of the heads.


New hydrolyzable tannins, shephagenins A and B, from Shepherdia argentea as HIV-1 reverse transcriptase inhibitors.
Two new hydrolyzable tannins, shephagenins A and B, were isolated along with hippophaenin A and strictinin from the leaf extract of Shepherdia argentea, which showed a remarkable inhibitory activity against human immunodeficiency virus (HIV)-1 reverse transcriptase. Their structures, having a gluconic acid core, have been elucidated on the basis of spectroscopic and chemical methods. The inhibitory effect of the leaf extract on HIV-1 reverse transcriptase was found to be due to tannins, and their activities were stronger than that of (-)-epigallocatechin gallate as a positive control.


Molecular analysis of vector genome structures after liver transduction by conventional and self-complementary adeno-associated viral serotype vectors in murine and nonhuman primate models.
Vectors based on several new adeno-associated viral (AAV) serotypes demonstrated strong hepatocyte tropism and transduction efficiency in both small- and large-animal models for liver-directed gene transfer. Efficiency of liver transduction by AAV vectors can be further improved in both murine and nonhuman primate (NHP) animals when the vector genomes are packaged in a self-complementary (sc) format. In an attempt to understand potential molecular mechanism(s) responsible for enhanced transduction efficiency of the sc vector in liver, we performed extensive molecular studies of genome structures of conventional single-stranded (ss) and sc AAV vectors from liver after AAV gene transfer in both mice and NHPs. These included treatment with exonucleases with specific substrate preferences, single-cutter restriction enzyme digestion and polarity-specific hybridization-based vector genome mapping, and bacteriophage phi29 DNA polymerase-mediated and double-stranded circular template-specific rescue of persisted circular genomes. In mouse liver, vector genomes of both genome formats seemed to persist primarily as episomal circular forms, but sc vectors converted into circular forms more rapidly and efficiently. However, the overall differences in vector genome abundance and structure in the liver between ss and sc vectors could not account for the remarkable differences in transduction. Molecular structures of persistent genomes of both ss and sc vectors were significantly more heterogeneous in macaque liver, with noticeable structural rearrangements that warrant further characterizations.


Au Nanoparticles Attenuate RANKL-Induced Osteoclastogenesis by Suppressing Pre-Osteoclast Fusion.
Osteoclasts are multinucleated terminal cells that originate from a hematopoietic monocyte/macrophage lineage. Excessive osteoclast formation in vivo can lead to bone metabolic diseases such as postmenopausal osteoporosis, multiple myeloma, rheumatoid arthritis, and lytic bone metastases of cancer cells. Au nanoparticles (AuNPs) are inorganic nanoparticles with outstanding biocompatibility. We assessed their effect on osteoclastogenesis and found that pre-osteoclast fusion induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF) was suppressed by AuNPs. Cell migration and actin ring formation were also significantly inhibited. Finally, AuNPs reduced osteoclast bone absorption function. Interestingly, we observed altered fusogenic gene expression in treated pre-osteoclasts. Our results suggest that AuNPs have potential as a therapeutic agent for osteoclast-related bone metabolism diseases.


RNA export: insights from viral models.
The retroviruses export intron-containing RNA. The complex retroviruses encode a Rev protein that uses a leucine-rich NES to interact with CRM1 and the U snRNA-export pathway. Other viruses encode proteins with a Rev-like NES. The type-D retroviruses contain a CTE that binds the cellular protein TAP to export intron-containing RNA through the mRNA pathway. Intronless viral transcripts contain post-transcriptionally acting RNA elements that may compensate for the lack of an intron. The functions of elements in intronless RNA are not fully understood but may be in export and/or 3'-end processing.


Mechanisms and Consequences of Oxygen and Carbon Dioxide Sensing in Mammals.
Molecular oxygen (O2) and carbon dioxide (CO2) are the primary gaseous substrate and product of oxidative phosphorylation in respiring organisms, respectively. Variance in the levels of either of these gasses outside of the physiological range presents a serious threat to cell, tissue, and organism survival. Therefore, it is essential that endogenous levels are monitored and kept at appropriate concentrations to maintain a state of homeostasis. Higher organisms such as mammals have evolved mechanisms to sense O2 and CO2 both in the circulation and in individual cells and elicit appropriate corrective responses to promote adaptation to commonly encountered conditions such as hypoxia and hypercapnia. These can be acute and transient nontranscriptional responses, which typically occur at the level of whole animal physiology or more sustained transcriptional responses, which promote chronic adaptation. In this review, we discuss the mechanisms by which mammals sense changes in O2 and CO2 and elicit adaptive responses to maintain homeostasis. We also discuss crosstalk between these pathways and how they may represent targets for therapeutic intervention in a range of pathological states.


Report on the inaugural meeting of the International Consortium on Hallucination Research: a clinical and research update and 16 consensus-set goals for future research.
This article presents a report on the first meeting of the International Consortium on Hallucination Research, which took place on September 13-14, 2011 at the Institute of Psychiatry, London. The first day of the meeting served to reflect on the current state of knowledge regarding auditory hallucinations in different diagnostic groups, based on the presentations from the phenomenology, cognition, emotion, electrophysiology, neurochemical, neuroimaging, genetics, treatment, and computational modeling working groups. The second day comprised a discussion forum where the most important and urgent questions for future research were identified. The meeting recognized that a lot has been achieved in auditory hallucination research but that much still remains to be done. Here, we outline the top 16 goals for research on auditory hallucinations, which cover topics of conceptual importance, academic and treatment issues, scientific rigor, and cross-disciplinary collaboration. Concerted and coordinated actions will be required to make substantial research progress.


Role of the potassium channels in vasorelaxant effect of asafoetida essential oil.
In a previous work, we showed that asafoetida essential oil (AEO), from oleo-gum resin of Ferula asafoetida L. from the Apiaceae family, has a vasodilatory effect. This effect was both endothelium-dependent and endothelium-independent. The present study was designed to determine whether potassium channels and intracellular calcium release contribute to AEO-induced vasodilation. Rats' thoracic aorta were isolated and denuded. Following induction of contraction by potassium chloride (60 mM), concentration-response curve was plotted by the cumulative addition of AEO (0.625-80 µl/l to the medium of rings. The vasodilatory effect of AEO was assessed before and after addition of phenylephrine and potassium channel blockers (including barium chloride (BC), 4-aminopyridine (4A) and glibenclamide (Gl)). AEO relaxed the precontracted rings in a concentration-dependent manner (IC50=23 µl/l). All potassium channel blockers significantly attenuated the vasodilatory activity of AEO when they were added to rings medium before addition of KCl (p<0.01, 4A and Gl groups and p< 0.001, BC group vs. control group) but not after that. In contrast to K channel blockers, adding AEO before or after phenylephrine, the tension was reduced significantly (p<0.05 vs. the control group). The findings of this study indicated that the vasodilatory effect of AEO on denuded-endothelium aortic ring was mediated through activation of potassium channels and reduced intracellular calcium release.


Identifying and mobilizing social supports for the cardiac patient's family.
This article emphasizes the importance of social supports to the cardiac patient's family as members deal with illness-created stress and needs. The dynamic nature of social support and factors contributing to its complexity are discussed. The article describes approaches to identifying and mobilizing the family's natural social supports.


Relationship between peripheral and central venous pressures in different patient positions, catheter sizes, and insertion sites.
To investigate the relationship between peripheral and central venous pressures in different patient positions (supine, prone, lithotomy, Trendelenburg, and Fowler), different catheter diameters (18 G and 20 G), and catheterization sites (dorsal hand and forearm) during surgical procedures. Prospective clinical study. University hospital. Five hundred adult patients. Peripheral over-the-needle intravenous catheters were placed in the dorsal hand or forearm. Central venous catheters were inserted via the internal jugular or subclavian vein after induction of anesthesia. Simultaneous measurements of central and peripheral venous pressures were made during stable conditions at random time points in surgery; 1953 paired measurements were performed. Mean central venous pressure was 11 +/- 3.7 mmHg and peripheral venous pressure was 13 +/- 4 mmHg (p = 0.0001). The overall correlation between central venous and peripheral venous pressures was found to be statistically significant (r = 0.89, r(2) = 0.8, p = 0.0001). Mean difference between peripheral and central venous pressure was 2 +/- 1.8 mmHg. Ninety-five percent limits of agreement were 5.6 to -1.6 mmHg. It has been assumed that replacing central venous pressure by peripheral venous pressure would cause problems in clinical interpretation. If the validity of this data is confirmed by further studies, the authors suggest that central venous pressure could be estimated by using regression equations to compare the 2 methods.


The silvering process of European eel (Anguilla anguilla) influences PAH metabolite concentrations in bile fluid: consequences for monitoring.
The stock of the catadromous European eel (Anguilla anguilla L.) continues to decline and there is growing evidence that poor health status due to contaminants might be a key element in this decrease. Organic contaminants such as polycyclic aromatic hydrocarbons (PAHs) belong to the major threats to yellow eel in their growth habitat and their metabolites are detectable in the bile. Starting the silvering process eels undergo physiological and morphological changes including cessation of feeding and downstream migration back to their spawning grounds. Reduced feed intake results in a diminishment of bile production and induces accumulation of e.g. PAH-metabolites in bile. Therefore, the aim of the present study was to demonstrate the impact of silvering on biliary PAH metabolite concentrations and to utilize normalization procedures to overcome silvering related accumulation effects of PAH-metabolites in eel bile. We investigated the hydroxyl-metabolites of pyrene (1-OH Pyr) and phenantrene (1-OH Phen) in the bile of different maturation stages of eels (silvering index I-V) from nine German rivers. We detected increasing absolute PAH metabolite levels in bile during the silvering process. The highest rise could be observed at the transition from pre migration stage III to the migrating stage IV, suggesting the onset of cessation of feeding at this stage. A cessation bias in PAH metabolite measurement could be diminished by normalization of absolute values against bile pigments (A(380), biliverdin). In conclusion, we demonstrated the impact of silvering on PAH metabolite concentrations in eel bile and present suitable normalization procedures to overcome silvering related accumulation effects. Thus, for a future eel monitoring we recommend (1) to regularly monitor PAH metabolites in bile, (2) to determine silvering index of eel and (3) to normalize PAH metabolite values in bile based on maturation/silvering stages. The knowledge of the silvering stage is mandatory for an unbiased evaluation of PAH contamination of European eel towards an international harmonized eel monitoring program.


Motion limitations of non-contact photoplethysmography due to the optical and topological properties of skin.
Non-contact photoplethysmography (PPG) provides multiple benefits over in-contact methods, but is not as tolerant to motion due to the lack of mechanical coupling between the subject and sensor. One limitation of non-contact photoplethysmography is discussed here, specifically looking at the topology and optical variations of the skin and how this impacts upon the ability to extract a photoplethysmogram when a subject moves horizontally across the field of view of the detector (a panning motion). When this occurs it is shown that whilst the general relationships between the speed of traversal, detection area and resultant signal quality can be found, the quality of signal in each individual case is determined by the properties of the area of skin chosen.


Prevalence of hepatitis B and C virus infection among leprosy patients in a leprosy-endemic region of central Brazil.
Leprosy and hepatitis B virus (HBV) are highly endemic in some regions of the state of Mato Grosso, in central Brazil. The association of leprosy with HBV and hepatitis C virus (HCV) was assessed using a seroprevalence study and 191 leprosy outpatients were included. Demographic data and the clinical classification of leprosy were recorded. Evidence of previous HBV infection was present in 53 patients (27.7%, 95% confidence interval: 21.9-34.5) and two (1%) were HBsAg positive. Five (2.6%) had antibodies to HCV. The prevalence of previous exposure to HBV was higher than expected for an adult population in central Brazil. In contrast, the prevalence of anti-HCV antibodies was not much higher regarding the age range of participants. HBV markers were associated with a higher number of sex partners and the use of injections without proper sterilisation of the syringes. The number of HBV carriers was small, suggesting that there was no increased likelihood of chronification among these patients.


Liver disease in alcohol abusers: clinical perspective.
Alcoholic liver disease remains one of the most common causes of chronic liver disease in the world. The severity of liver damage related to alcohol varies among different individuals and even within any given individual at different times. Certain symptoms, signs, and abnormal findings on laboratory tests help clinicians distinguish among the various stages of alcohol-induced liver damage and, thus, have some prognostic significance. However, because all stages of this disease can persist for decades without causing overt evidence of serious liver damage, liver biopsy is the only test that can reliably distinguish among the various stages of alcohol-induced liver damage in many patients. The therapy of alcohol-induced liver disease varies according to the severity of histologic liver damage and clinically overt portal hypertension and hepatic dysfunction. Abstinence from alcohol consumption improves the clinical outcome of all stages of alcoholic liver disease. However, only two agents have proved to lessen early mortality in patients who require hospitalization for acutely decompensated alcoholic liver disease. It is not known whether either of these agents or other treatments prevent the development of alcohol-induced cirrhosis or improve the survival of patients who have already developed cirrhosis.


Five-year experience of human immunodeficiency virus type 1 national screening program implemented at Veterans General Hospital-Taipei.
From July 1986 through June 1990, 33,199 sera from various risk groups were collected in Veterans General Hospital-Taipei for detection of antibody against human immunodeficiency virus, type 1 (HIV-1). Sixty-five samples were proved positive by Western blot analysis. Among individual high risk groups, hemophiliacs had the highest positive rate of 20/60 (29.41%), followed by homosexual/bisexual males (41/1,264, 3.24%). The overall positive rate was 65/33,199 (0.19%). Ten cases were recognized as acquired immunodeficiency syndrome (AIDS), 1 case had AIDS-related complex (ARC) and 4 case had other apparently symptomatic infections. Among these 15 cases, 7 expired, 1 lost of follow-up and 7 surviving cases are being treated with zidovudine (AZT). Most of symptomatic HIV-1 antibody positive cases had abnormal T4/T8 ratio of 0.39 +/- 0.54 as compared with the asymptomatic HIV-1 carriers at a ratio of 0.81 +/- 0.69. The opportunistic infections included Pneumocystis carinii pneumonia (PCP) in 6 case, disseminated cytomegalovirus infection in 6 cases, herpes zoster virus infection in 3 case, candidiasis in 4 cases, syphilis in 3 cases, pulmonary tuberculosis in 2 cases, and others with cryptococcosis, salmonellosis, Mycobacterium avium-intracellulare infection, gonorrhea, Staphylococcus aureus endocarditis and bacterial sepsis, etc. The natural history of HIV-1 infection to AIDS involved acute and persistent multiple infections. Although prevalence of HIV-1 infection was low in Taiwan, nationwide surveillance of HIV-1 infection in various risk groups is still needed.


Developing a cerebral palsy-specific preference-based measure for a six-dimensional classification system (CP-6D): protocol for a valuation study.
Cerebral palsy (CP) is a lifelong condition. The CP quality of life (CPQOL) instrument is a frequently used disease-specific instrument to assess health-related quality of life (HRQoL) in people with CP, but it cannot be used to generate quality-adjusted life years (QALY) which are the basis of cost utility analysis (CUA). Generic utility instruments (such as the EQ-5D or SF-6D) that are used to value HRQOL may be insensitive to small but important health changes in children with CP. This study aims to generate a preference-based scoring algorithm for the CP six dimensions (CP-6D), a classification system developed from the CPQOL. A discrete choice experiment with duration (DCEtto) will be administrated to value health states described by the CP-6D classification system. These health states will be presented to members of Australian general population and parents of children with CP via an online survey. Conditional logit regression will be used to produce the utility algorithm for CP-6D. The Griffith University Human Research Ethics Committee approved for the study (reference HREC/number 2018/913). The developed algorithm can be applied to previous and future economic evaluation of interventions and treatments targeting people with CP which have used either the CPQOL or CP-6D.


Learning as an empowerment process in breast cancer self-help groups.
This intervention study aimed to promote and examine empowerment processes in women recovering from breast cancer and participating in self-help groups. Feelings of powerlessness may follow from being diagnosed and treated for breast cancer. In theory, self-help groups may stimulate empowerment, which stands in contrast to powerlessness, by increasing the participants' sense of control. Professional assistance may contribute positively, by assuring that the issue of empowerment is addressed. The study had an intervention design based on the ideas of empowerment and self-help. Three professionally led self-help groups were established. The groups ran sequentially and met weekly for approximately four months. Eighteen women in groups of 5-7 participated in self-help group discussions and also in focus group interviews, which provided the main study data. Each group was interviewed three times. Observation data provided a basis for comprehension of the groups' culture, relationships and processes. Learning appeared as one of three salient components in empowerment processes in the self-help groups. This learning component consists of four elements: consciousness-raising, acquisition of objective knowledge, learning from others' experiences and discovery of new perspectives in life and in oneself. The study shows that self-help groups focusing on empowerment issues made a valuable contribution to recovery and are strongly recommended by the participants. This study suggests that best practice, for those who manage self-help programmes of all types, may be to arrange for empowerment to be an explicit aspect of the intervention, guided by professionals with training in group facilitation and knowledgeable about the facilitation of empowerment in particular.


Low virus to prokaryote ratios in the cold: benthic viruses and prokaryotes in a subpolar marine ecosystem (Hornsund, Svalbard).
The density and spatial distribution of benthic viruses and prokaryotes in relation to biotic and abiotic factors were investigated in sediment cores collected in Hornsund, a permanently cold fjord on the West coast of Svalbard, Norway. The cores were obtained from the mouth of the fjord to the central basin, along a longitudinal transect. The results of our analyses showed lower densities of viruses (0.2 x 10(8) to 5.4 x 10(8) virus-like particles/g) and lower virus-to-prokaryote ratios (0.2-0.6, with the exception of the uppermost layer in the central basin, where the ratio was about 1.2) at the study site than generally found in the temperate areas, despite the relatively high organic matter content in subpolar sediments. Variations in benthic viral and prokaryote abundances along gradients of particle sedimentation rates, phytopigment concentrations, and macrobenthic species composition together suggested the influence of particle sedimentation and macrobenthic bioturbation on the abundance and spatial distribution ofprokaryotes and viruses in cold habitats.


On the Etiology of Molar-Incisor Hypomineralization.
Molar-incisor hypomineralization (MIH) is a condition that is defined based on its peculiar clinical presentation. Reports on the etiology of the condition and possible risk factors are inconclusive and the original suggestion that MIH is an idiopathic condition is often cited. Our group was the first to suggest MIH has a genetic component that involves genetic variation in genes expressed during dental enamel formation. In this report, we provide a rationale to explain the preferential affection of molars and incisors. We suggest that MIH is a genetic condition based on its prevalence, which varies depending on the geographic location, and the evidence that on occasion second primary molars, permanent canines, and premolars can show signs of hypomineralization of enamel when molars and incisors are affected.


Carpal scaphoid fracture in the skeletally immature: a single centre one-year prospective study.
We report up-to-date one-year prospective data on the incidence of scaphoid fracture in skeletally immature patients managed in a Fracture Clinic of a Level I Trauma Centre in a University Hospital in the UK. All scaphoid fractures were immobilised until union was achieved. One hundred twenty one skeletally immature patients were referred for a suspected fracture of the scaphoid. Fourteen patients (11.5%) did have a scaphoid fracture, an incidence of 15 per 100,000 (0.55% of all paediatric injuries referred). Mean delay in being seen was 2.6 days, and mean follow-up time was 52.3 days. Only plain radiography was used to diagnose and follow up scaphoid fractures. Fractures of the scaphoid in skeletally immature individuals are uncommon, are usually undisplaced, occur more commonly in the distal portion of the bone, and carry a good prognosis.


Idiopathic Orbital Inflammation Presenting with Bilateral Panuveitis.
Idiopathic orbital inflammation or orbital pseudotumor is rare in the pediatric population and may present with ocular findings not normally seen in the adult population. The authors report the case of a 14-year-old boy with idiopathic orbital inflammation who presented with bilateral panuveitis to highlight the features that make this diagnosis more difficult in the pediatric population.


[Preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and further studies on pharmacokinetics in rats].
In this paper, we address the preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and report the data collected from further studies on pharmacokinetics in blood for choosing a better carrier in delivering the drugs. The pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC-SSL, and HEPC-SSL) in Wistar rats were investigated by HPLC. The results showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h. In conclusion, HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites when compared with EPC-SSL.


Computational and in vitro validation of cardiogenic induction of quercetin on adipose-derived mesenchymal stromal cells through the inhibition of Wnt and non-Smad-dependent TGF-β pathways.
Exploiting human mesenchymal stem cells (hMSCs) was proposed as a promising therapeutic approach for cardiovascular disease due to their capacity to differentiate into cardiac cells. Though modulation of the intracellular signaling pathways dominantly WNT/β catenin and transforming growth factor-β (TGF-β) have been reported to promote differentiation of hMSCs into cardiomyocytes in the prevailing literature, a safe and reproducible system for their clinical application has not yet turned into reality. In the present study, the molecular docking-based strategy was first applied for evaluating the potency of some natural phenolic compounds in the modulation of Wnt and TGF-β signaling pathways using a vital class of crystallographic protein structures of WNT signaling regulators such as Frizzled, Disheveled, GSK3-β, β-catenin, LRP 5/6 extracellular domain, Tankyrase and their variety of active pockets. Then, the impacts of plant-derived chemical compounds on the regulation of the relevant signals for the differentiation of hMSCs into the definitive mesoderm lineage and cardiac progenitors were assessed in vitro. Data obtained revealed the synergistic activity of Wnt and TGF-β superfamily to direct cardiac differentiation in human cardiogenesis by comparing cardiac gene expression in the presence and absence of the TGF-β inhibitors. We found that the inhibitory effect of canonical Wnt/β-catenin is sufficient to cause proper cardiomyocyte differentiation, but the TGF-β pathway plays a vital role in enhancing the expression of the cardiomyocyte-specific marker (cTnT). It was found that quercetin, a p38MAPK inhibitor with the high energy dock to the active pocket of Wnt receptors, promotes cardiac differentiation via the inhibition of both Wnt and non-Smad TGF-β pathways. Altogether, data presented here can contribute to the development of a feasible and efficient cardiac differentiation protocol as an "off-the-shelf" therapeutic source using novel natural agents for cardiac repair or regeneration.


Fetal globin gene inducers: novel agents and new potential.
Inducing expression of endogenous fetal globin (gamma-globin) gene expression to 60-70% of alpha globin synthesis produces beta-thalassemia trait globin synthetic ratios and can reduce anemia to a mild level. Several classes of therapeutics have induced gamma-globin expression in beta-thalassemia patients and subsequently raised total hemoglobin levels, demonstrating proof-of-concept of the approach. Butyrate treatment eliminated transfusion requirements in formerly transfusion-dependent patients with treatment for as long as seven years. However, prior generation inducers were not readily applicable for widespread use. Currently, a novel oral dual-action therapeutic, sodium 2,2-dimethylbutyrate, is in clinical trials, an oral decitabine formulation is under development, and agents with complementary mechanisms of action can be applied in combined regimens. Identification of three major genetic trait loci which modulate clinical severity provides avenues for developing tailored regimens. These refinements offer renewed potential to apply fetal globin induction as a treatment approach in patient-friendly regimens that can be used worldwide.


Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area.
Peptide vaccine strategies using Plasmodium-derived antigens have emerged as an attractive approach against malaria. However, relatively few studies have been conducted with malaria-exposed populations from non-African countries. Herein, the seroepidemiological profile against Plasmodium falciparum of naturally exposed individuals from a Brazilian malaria-endemic area against synthetic peptides derived from vaccine candidates circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein-3 (MSP-3) was investigated. Moreover, human leukocyte antigen (HLA)-DRB1* and HLA-DQB1* were evaluated to characterize genetic modulation of humoral responsiveness to these antigens. The study was performed using blood samples from 187 individuals living in rural malaria-endemic villages situated near Porto Velho, Rondônia State. Specific IgG and IgM antibodies and IgG subclasses were detected by enzyme-linked immunosorbent assay, and HLA-DRB1* and HLA-DQB1* low-resolution typing was performed by PCR-SSP. All four synthetic peptides were broadly recognized by naturally acquired antibodies. Regarding the IgG subclass profile, only CSP induced IgG1 and IgG3 antibodies, which is an important fact given that the acquisition of protective immunity appears to be associated with the cytophilicity of IgG1 and IgG3 antibodies. HLA-DRB1*11 and HLA-DQB1*7 had the lowest odds of responding to EBA-175. Our results showed that CSP, LSA-1, EBA, and MSP-3 are immunogenic in natural conditions of exposure and that anti-EBA antibody responses appear to be modulated by HLA class II antigens.


Deployment of e-health services - a business model engineering strategy.
We designed a business model for deploying a myofeedback-based teletreatment service. An iterative and combined qualitative and quantitative action design approach was used for developing the business model and the related value network. Insights from surveys, desk research, expert interviews, workshops and quantitative modelling were combined to produce the first business model and then to refine it in three design cycles. The business model engineering strategy provided important insights which led to an improved, more viable and feasible business model and related value network design. Based on this experience, we conclude that the process of early stage business model engineering reduces risk and produces substantial savings in costs and resources related to service deployment.


Characterization of nonspecific crossover in split-flow thin channel fractionation.
Split-flow thin channel (SPLITT) fractionation is a technique for continuous separation of particles or macromolecules in a fluid stream into fractions according to the lateral migration induced by application of a field perpendicular to the direction of flow. Typical applications have involved isolation of different fractions from a polydisperse sample. Some specialized applications involve the separation of the fraction influenced by the transverse field from the fraction that is not. For example, immunomagnetically labeled biological cells may be separated from nonlabeled cells with the application of a transverse magnetic field gradient. In such cases, it may be critically important to minimize contamination of the labeled cells with nonlabeled cells while at the same time maximizing the throughput. Such contamination is known as nonspecific crossover (NSC) and refers to the real or apparent migration of nonmobile particles or cells across stream lines with the mobile material. The possible mechanisms for NSC are discussed, and experimental results interpreted in terms of shear-induced diffusion (SID) caused by viscous interactions between particles in a sheared flow. It is concluded that SID may contribute to NSC, but that further experiments and mathematical modeling are necessary to more fully explore the phenomenon.