Application of microfluidic devices in studies of thrombosis and hemostasis.
Due to the importance of fluid flow during thrombotic episodes, it is quite appropriate to study clotting and bleeding processes in devices that have well-defined fluid shear environments. Two common devices for applying these defined shear stresses include the cone-and-plate viscometer and parallel-plate flow chamber. While such tools have many salient features, they require large amounts of blood or other protein components. With growth in the area of microfluidics over the last two decades, it has become feasible to miniaturize such flow devices. Such miniaturization not only enables saving of precious samples but also increases the throughput of fluid shear devices, thus enabling the design of combinatorial experiments and making the technique more accessible to the larger scientific community. In addition to simple flows that are common in traditional flow apparatus, more complex geometries that mimic stenosed arteries and the human microvasculature can also be generated. The composition of the microfluidics cell substrate can also be varied for diverse basic science investigations, and clinical investigations that aim to assay either individual patient coagulopathy or response to anti-coagulation treatment. This review summarizes the current state of the art for such microfluidic devices and their applications in the field of thrombosis and hemostasis.


GENETIC CONSTRAINTS ON THE INDEPENDENT EVOLUTION OF MALE AND FEMALE REPRODUCTIVE CHARACTERS IN THE TRISTYLOUS PLANT LYTHRUM SALICARIA.
Here we test whether the potential exists for the independent evolution of allocation to male, female, and attractive functions within a flower. We employed half-sib and parent-offspring regression methods in the tristylous plant Lythrum salicaria to determine whether there is additive genetic variation for characters important to male and female reproductive success and whether genetic correlations could constrain the independent evolution of male and female function. Although significance levels were not consistent among morph types or between populations, there were significant narrow-sense heritabilities for several traits including stamen mass, pistil mass, perianth mass, petal length, and calyx length. Traits that might be under strong stabilizing selection to promote specific pollen transfer, such as stamen and style lengths, had little heritable variation. In the majority of cases in which heritable variation was present, there were positive genetic correlations among floral traits. A strong positive genetic correlation appeared between stamen and pistil mass in the short-styled morph from one of the populations studied. This suggests that selection might not be able to act independently on biomass allocation to male and female flower parts. No evidence of negative genetic correlations appeared that would suggest trade-offs and that could augment a selection response towards sexual specialization. The observed positive correlations could be explained if we consider the "functional architecture" that underlies the covariance structure. If there is more covariance generated by pleiotropic loci controlling overall flower size than at loci controlling male versus female allocation, it could result in the observed positive covariance. At the phenotypic level, we did find significant negative partial correlations between male and female traits when flower size was controlled, but these trade-offs were among rather than within morphs.


Effect of platelet-rich plasma for treatment of Achilles tendons in free-moving rats after surgical incision and treatment.
The purpose of this study is to investigate, both histopathologically and biomechanically, the effect of platelet-rich plasma (PRP) on surgically repaired Achilles tendon rupture recovery in rats. The study included 25 17-month-old male Sprague-Dawley rats with an average weight of 500-550 g. Five rats were used as donors, while 20 rats were separated as PRP group (n=10) and control group (n=10). The Achilles tendons of the rats were cut transversely, and PRP was administered to the PRP group, while the control group received serum physiologically to create the same surgical effect. In previous studies, it was shown that this serum does not affect tendon recovery. Fifteen and 30 days post-treatment, the rats were sacrificed, and their Achilles tendons were extracted and examined histopathologically and biomechanically. Based on the obtained findings, it was observed that the histopathologic Movin and Bonar scores of PRP group on the 15th and 30th day post-treatment were significantly lower than those of the control group (p=0.019, p=0.017, respectively), while no significant difference was found in maximum force (Fmax) values in biomechanical measures on the 15th and 30th day post-treatment. It is thought that PRP use in Achilles tendon ruptures positively affects histopathological recovery in the early period, but that it does not produce the same biomechanical effect. We believe that PRP use for qualified tendon recovery is histopathologically beneficial.


Emphysema-like changes in the lungs of the blotchy mouse.
The Blotchy allele is one of several mutations at the Mottled locus on the mouse X-chromosome. Affected males and heterozygous females within the several allelic groups possess varying degrees of connective tissue abnormalities similar to those found in copper-deficient and lathyritic animals, including aortic aneurysms and reduced skin tensile strength. There is evidence that defective inter- and intramolecular cross-links in collagen and elastin account for these abnormalities. The lung of the Blotchy mouse is also structurally and functionally abnormal. Hemizygous males have larger total lung volumes, markedly increased mean linear intercepts, and diminished internal alveolar surface area when compared to normal control animals. Light microsbopy and scanning electron microscopy show abnormal architecture with enlargement of air spaces and effacement of alveolar septa. Static air and saline pressure-volume curves show that lungs of Blotchy mice have decreased elastic recoil and are significantly more compliant than normal. These abnormalities in the lung of the Blotchy mouse suggest that the defects of the connective tissue proteins described in skin and aorta also involve the lung. The Blotchy strain may be a useful model in which to investigate how abnormalities of connective tissue proteins influence pulmonary structure and function.


Epidemiologic evidence of transmission of donor-related bacterial infection through a transplanted heart.
This study describes a patient who had fulminant infectious myocarditis as a result of methicillin-resistant Staphylococcus aureus after receiving a heart transplant from an infected donor. There was complete concordance of typing results between donor and recipient strains that were different from the 20 isolates with which they were compared. Molecular epidemiologic study provided compelling evidence that a transplanted organ can transmit a bacterial infection from the donor to the recipient.


Exchange of Vitamin B1 and Its Biosynthesis Intermediates Shapes the Composition of Synthetic Microbial Cocultures and Reveals Complexities of Nutrient Sharing.
Microbial communities occupy diverse niches in nature, and community members routinely exchange a variety of nutrients among themselves. While large-scale metagenomic and metabolomic studies shed some light on these exchanges, the contribution of individual species and the molecular details of specific interactions are difficult to track. In this study, we follow the exchange of vitamin B1 (thiamin) and its intermediates between microbes within synthetic cocultures of Escherichia coli and Vibrio anguillarum. Thiamin contains two moieties, 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) and 4-methyl-5-(2-hydroxyethyl)thiazole (THZ), which are synthesized by distinct pathways using enzymes ThiC and ThiG, respectively, and then coupled by ThiE to form thiamin. Even though E. coli ΔthiC, ΔthiE, and ΔthiG mutants are thiamin auxotrophs, we observed that cocultures of ΔthiC-ΔthiE and ΔthiC-ΔthiG mutants are able to grow in a thiamin-deficient medium, whereas the ΔthiE-ΔthiG coculture does not. Further, the exchange of thiamin and its intermediates in V. anguillarum cocultures and in mixed cocultures of V. anguillarum and E. coli revealed that there exist specific patterns for thiamin metabolism and exchange among these microbes. Our findings show that HMP is shared more frequently than THZ, concurrent with previous observations that free HMP and HMP auxotrophy is commonly found in various environments. Furthermore, we observe that the availability of exogenous thiamin in the media affects whether these strains interact with each other or grow independently. These findings collectively underscore the importance of the exchange of essential metabolites as a defining factor in building and modulating synthetic or natural microbial communities. IMPORTANCE Vitamin B1 (thiamin) is an essential nutrient for cellular metabolism. Microorganisms that are unable to synthesize thiamin either fully or in part exogenously obtain it from their environment or via exchanges with other microbial members in their community. In this study, we created synthetic microbial cocultures that rely on sharing thiamin and its biosynthesis intermediates and observed that some of them are preferentially exchanged. We also observed that the coculture composition is dictated by the production and/or availability of thiamin and its intermediates. Our studies with synthetic cocultures provide the molecular basis for understanding thiamin sharing among microorganisms and lay out broad guidelines for setting up synthetic microbial cocultures by using the exchange of an essential metabolite as their foundation.


[Chemical constituents of Periploca forrestii].
To study the constituents of the stems of Periploca forrestii. The compounds were separated and purified by silica gel column chromatography, recrystallization and high-performance liquid chromatography. The structures were identified by various spectroscopic methods. Nine compounds were isolated and identified as 3-O-acetyloleanolic acid (1), 14-ursen-3-ol-1-one (2), taraxasterol (3), jacoumaric acid (4), periplogenin (5), 2alpha,3beta-dihydroxyursolic acid (6), E-p-hydroxy-cinnamic acid (7), caffeic acid (8), proanthocyanidin A2 (9). All compounds except 6 were isolated from this plant for the first time, compound 4, 9 were obtained from the Periploca for the first time.


Protective Effects of Functional Chicken Liver Hydrolysates against Liver Fibrogenesis: Antioxidation, Anti-inflammation, and Antifibrosis.
Via an assay using an Amino Acid Analyzer, pepsin-digested chicken liver hydrolysates (CLHs) contain taurine (365.57 ± 39.04 mg/100 g), carnosine (14.03 ± 1.98 mg/100 g), and anserine (151.58 ± 27.82 mg/100 g). This study aimed to evaluate whether CLHs could alleviate thioacetamide (TAA)-induced fibrosis. A dose of 100 mg TAA/kg BW significantly increased serum liver damage indices and liver cytokine contents. Cell infiltration and monocytes/macrophages in livers of TAA-treated rats were illustrated by the H&E staining and immunohistochemical analysis of cluster of differentiation 68 (CD68, ED1), respectively. A significantly increased hepatic collagen accumulation was also observed and quantified under TAA treatment. A significant up-regulation of transforming growth factor-beta (TGF-β) and SMAD family member 4 (SMAD4) caused by TAA treatment further enhanced alpha smooth muscle actin (αSMA) gene and protein expressions. The liver antioxidant effects under TAA treatment were significantly amended by 200 and 600 mg CLHs/kg BW. Hence, the ameliorative effects of CLHs on liver fibrogenesis could be attributed by antioxidation and anti-inflmmation.


Detection and Clinical Implications of Monovalent Rotavirus Vaccine-Derived Virus Strains in Children with Gastroenteritis in Alberta, Canada.
While rotavirus vaccine programs effectively protect against severe rotavirus gastroenteritis, rotavirus vaccine strains have been identified in the stool of vaccinated children and their close contacts suffering from acute gastroenteritis. The prevalence of vaccine strains, the emergence of vaccine-derived strains, and their role in acute gastroenteritis are not well studied. We developed a locked nucleic acid reverse transcription real-time PCR assay (LNA-RTqPCR) to detect the monovalent rotavirus vaccine (RV1) Rotarix nonstructural protein 2 (NSP2) in children with acute gastroenteritis and healthy controls, and validated it using sequence-confirmed RV1 strains. The association between RV1-derived strains and gastroenteritis was determined using logistic regression. The new assay exhibited 100% (95% CI 91.7%, 100%) diagnostic sensitivity and 99.4% (95% CI 96.2%, 100%) diagnostic specificity, with a detection limit of 9.86 copies/reaction and qPCR efficiency of 99.7%. Using this assay, we identified the presence of RV1-derived NSP2 sequences in 7.7% of rotavirus gastroenteritis cases and 98.6% of rotavirus-positive healthy children (94.4% had previously received the RV1). Among gastroenteritis cases, those whose stool contained RV1-derived strains had milder gastroenteritis symptoms compared to that of natural rotavirus infections. We observed no significant association between RV1-derived strains and gastroenteritis (odds ratio [OR] 0.98; 95% CI 0.60, 1.72). Our study demonstrated that the new assay is suitable for monitoring RV1-derived rotavirus strain circulation and that the RV1-derived strains are not associated with development of gastroenteritis symptoms.


New pharmacological findings in depression.
The last decade of psychopharmacological research in depression is characterised by the development of structurally novel and biochemically selective-acting drugs and by the shift of interest from the acute to long-term treatment effects of antidepressants on catecholaminergic transmission. Of particular importance in this respect are the findings demonstrating adaptative changes occurring at receptor levels which have led to alternative theoretical formulations about the origin of depression and the mode of action of antidepressants. However in spite of the progress in this field of research the mechanism of therapeutic action of antidepressants remains unknown. Examples of drugs not affecting NA and 5-HT uptake or release and producing no adaptative changes of adrenergic receptors (trimipramine, levoxaprotiline) indicate that antidepressant-like activity can be achieved by mechanisms which still remain to be elucidated.


Dipstick screening for urinary tract infection.
In screening for urinary tract infection the leucocyte esterase test will detect almost all samples with significant pyuria and bacteriuria, but is relatively nonspecific. The nitrite test is more specific but less sensitive and about one-third of the urinary tract infections in a large group of children were missed. The combination of screening tests results in greater overall accuracy both in the diagnosis and exclusion of urinary tract infection. Almost all cases of urinary tract infection were detected when either the leucocyte esterase or the nitrite screening test or both were positive. If both tests are negative, urinary tract infection is virtually excluded and unless the child is symptomatic, further urinalysis is unnecessary. Laboratory urinalysis is, however, necessary if any one screening test for leucocyte esterase or nitrite (or protein or haemoglobin) is positive. Combined biochemical screening for urinary tract infection with dipstick test strips is reliable and allows early diagnosis and management. By avoiding unnecessary urinalysis it is cost-effective for the patient and will significantly reduce the laboratory workload.


Without nerves, immunology remains incomplete -in vivo veritas.
Interest in the interactions between nervous and immune systems involved in both pathological and homeostatic mechanisms of host defence has prompted studies of neuroendocrine immune modulation and cytokine involvement in neuropathologies. In this review we concentrate on a distinct area of homeostatic control of both normal and abnormal host defence activity involving the network of peripheral c-fibre nerve fibres. These nerve fibres have long been recognized by dermatologists and gastroenterologists as key players in abnormal inflammatory processes, such as dermatitis and eczema. However, the involvement of nerves can all too easily be regarded as that of isolated elements in a local phenomenon. On the contrary, it is becoming increasingly clear that neural monitoring of host defence activities takes place, and that involvement of central/spinal mechanisms are crucial in the co-ordination of the adaptive response to host challenge. We describe studies demonstrating neural control of host defence and use the specific examples of bone marrow haemopoiesis and contact sensitivity to highlight the role of direct nerve fibre connections in these activities. We propose a host monitoring system that requires interaction between specialized immune cells and nerve fibres distributed throughout the body and that gives rise to both neural and immune memories of prior challenge. While immunological mechanisms alone may be sufficient for local responsiveness to subsequent challenge, data are discussed that implicate the neural memory in co-ordination of host defence across the body, at distinct sites not served by the same nerve fibres, consistent with central nervous mediation.


Approaches to patient health information exchange and their impact on emergency medicine.
Regional health information organizations and electronic health information exchange may have an important impact on the practice of emergency medicine in the United States. Regional health information organizations are local or regional information-sharing networks that enable electronic data interchange among stakeholders in a given geographic area. These stakeholders may include hospitals, skilled nursing facilities, clinics, private physicians' offices, pharmacies, laboratories, radiology facilities, health departments, payers, and possibly the patients themselves. Regional health information organizations are being formed across the country to improve the safety and efficiency of clinical care; improve public health efforts, biosurveillance, and disaster management response; and potentially create large databases of deidentified aggregate data for research. Because of the unique need for rapid access to information and the acuity of the clinical environment, few areas of the health care delivery system stand to change and benefit more from health information exchange than our nation's emergency departments. This article will explain the motivation for the development of regional health information organizations, identify some of the important issues in their formation, and discuss how their development might affect the practice of emergency medicine.


Solitary Fibrous Tumor of the Stomach.
Solitary fibrous tumor is a rare mesenchymal neoplasm that usually originates from the pleura, but has been reported in other extrapleural locations. We report a rare case of a solitary fibrous tumor of the stomach, which was successfully treated with endoscopic mucosal resection.


Efficacy and safety of 9 nonoperative regimens for the treatment of spinal cord injury: A network meta-analysis.
This network meta-analysis aims to compare the efficacy and safety of 9 nonoperative regimens (placebo, pregabalin, GM-1 ganglioside, venlafaxine extended-release [venlafaxine XR], fampridine, conventional over-ground training [OT], body-weight-supported treadmill training [BWSTT], robotic-assisted gait training [RAGT] + OT and body-weight-supported over-ground training [BWSOT]) in treating spinal cord injury (SCI). Clinical controlled trials of 9 nonoperative regimens for SCI were retrieved in the electronic database. Traditional pairwise and Bayesian network meta-analyses were performed to compare the efficacy and safety of 9 nonoperative regimens for the treatment of SCI. Weighted mean difference (WMD), odds ratios (OR), and surface under the cumulative ranking curve (SUCRA) were calculated using the Markov Chain Monte Carlo engine Open BUGS (V.3.4.0) and R (V.3.2.1) package gemtc (V.0.6). A total of 9 clinical controlled trials meeting the inclusion criteria were selected in this meta-analysis. On the aspect of efficacy, the results of pairwise meta-analysis indicated that the RAGT + OT and BWSOT might have the best efficacy in SCI patients in terms of a lower extremity motor score (LEMS) compared with conventional OT; the efficacy of RAGT + OT on SCI patients was relatively better than that of conventional OT in terms of walking index for spinal cord injury (WISCI). With the aspect of safety, the constipation rate of placebo on SCI patients was relatively higher than that of venlafaxine XR; however, with respect to headache and urinary tract infection, there was no significant difference in the safety of placebo, pregabalin, GM-1 ganglioside, venlafaxine XR, and fampridine on SCI patients. The results of SUCRA values suggested that BWSOT had the highest SUCRA value (75.25%) of LEMS; RAGT + OT had the highest SUCRA value (88.50%) of WISCI; venlafaxine XR had the highest SUCRA value (94.00%) of constipation; venlafaxine XR had the highest SUCRA value (80.00%) of headache; GM-1 ganglioside had the highest SUCRA value (87.75%) of urinary tract infection. Our results provide evidence that the RAGT + OT and BWSOT might have the best efficacy in the treatment of SCI, and the venlafaxine XR and GM-1 ganglioside showed adequate safety for SCI.


Observations of chemical differentiation in clumpy molecular clouds.
We have extensively mapped a sample of dense molecular clouds (L1512, TMC-1C, L1262, Per7, L1389, L1251E) in lines of HC3N, CH3OH, SO and C18O. We demonstrate that a high degree of chemical differentiation is present in all of the observed clouds. We analyse the molecular maps for each cloud, demonstrating a systematic chemical differentiation across the sample, which we relate to the evolutionary state of the cloud. We relate our observations to the cloud physical, kinematical and evolutionary properties, and also compare them to the predictions of simple chemical models. The implications of this work for understanding the origin of the clumpy structures and chemical differentiation observed in dense clouds are discussed.


Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter.
Discs-large homolog 1 (DLGH1) is a mouse ortholog of the Drosophila discs-large (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein families. DLG proteins play important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function. Here, we generated a null allele of Dlgh1 and studied its role in urogenital development. Dlgh1(-/-) mice developed severe urinary tract abnormalities, including congenital hydronephrosis, which is the leading cause of renal failure in infants and children. DLGH1 is expressed in the developing ureter; in its absence, the stromal cells that normally lie between the urothelial and smooth muscle layers were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle cells were misaligned in a longitudinal orientation. These abnormalities in the ureter led to severely impaired ureteric peristalsis. Similar smooth muscle defects are observed frequently in patients with ureteropelvic junction obstruction, a common form of hydronephrosis. Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis.


Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia.
Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair, and methylation of DNA. We examined whether child's germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk. Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS), were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race. Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS, and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (p < 0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS. Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk.


High-rise healing for young cancer patients.
A "teenage penthouse" designed in consultation with patients and nurses with an "inspiring, homely feel", and conceived using "sensitive architecture" to support young people in their fight against cancer, is how architect John McRae of ORMS Architecture Design describes the award-winning new Teenage Cancer Trust (TCT) unit at the University Hospital of Wales in Cardiff. Jonathan Baillie reports.


Studies with chimeric Mpl/JAK2 receptors indicate that both JAK2 and the membrane-proximal domain of Mpl are required for cellular proliferation.
The thrombopoietin (TPO) receptor c-Mpl, like other members of the cytokine receptor superfamily, requires the association and activation of Janus kinases (JAKs) for normal signal transduction. The membrane-proximal portion of the signaling domain, containing conserved box1 and box2 motifs, is sufficient to support the proliferation of cytokine-dependent cell lines and basal megakaryocytopoiesis in vivo. We hypothesized that activation of the JAK2 kinase alone might be sufficient for proliferative signaling. To test this premise, we constructed chimeric receptors in which the extracellular and transmembrane portions of Mpl were fused to the pseudokinase and kinase domains of murine JAK2 kinase. When expressed in the interleukin-3-dependent cell line Ba/F3, the chimeric receptors were appropriately expressed on the cell surface and were able to initiate tyrosine kinase activity upon exposure to TPO. However, chimeric receptors lacking an intact box2 domain of Mpl were unable to support proliferation at any concentration of TPO. Only chimeric receptors containing both JAK2 kinase activity and the box2 region initiated proliferative signaling. Within the box2 motif, we determined that the sequence Glu(56)-Ile(57)-Leu(58) of the Mpl cytoplasmic domain is critical for proliferation of the chimeric receptors. Furthermore, TPO-dependent induction of c-myc transcription is also dependent on this motif. These results indicate that JAK2 activation alone is not sufficient for TPO-induced proliferation and that one or more essential signaling pathways must arise from the cytoplasmic domain of Mpl that includes box2. Although the nature of the signal transduction pathway is not yet known, this second proliferative event is likely to regulate c-myc expression.


Non-synaptic interaction between neurons in the brain, an analog system: far from Cajal-Sherringtons's galaxy.
The functional interactions between neurons without synaptic contacts are specialized to function on a time scale of seconds (minutes) and a distance scale of hundreds of micrometers. These nonsynaptic receptors and transporters are of high affinity, have many implications for psychiatry for understanding e.g. depression, changes in mood, in appetite, affective illnesses etc. It is, therefore, suggested that many drugs applied in psychiatric diseases, exert their effects after diffusion through extracellular spaces and may mimic the mode, or may influence the effect of endogenous ligands. The nonsynaptic chemical communication between neurons, and between neurones and target cells, via both pre- and postsynaptic sites, seems likely to achieve growing recognition. This system has a similar degree of selectivity to that of synaptic circuitry but have, in addition, a domain of versatility and plasticity in "hardwired" circuitry. The brain is a wired instrument, but its neurons, besides cabled information processing (through synapses), are able to talk to each other without synaptic contact. It is suggested, therefore that the nonsynaptic tonic presynaptic modulation of chemical transmission, plays a physiological role in the brain in shaping emotion, behaviour or learning processes, or in controlling the balance between sympathetic and parasympathetic nervous system, or the nonsynaptic released transmitter is able to produce responses of the target cells and a local fine tuning of cytokine production (cf. Elenkov et al., 2000), steroid secretion and possible many other functions not yet discovered. The spatial and temporal effect of transmitters on nonsynaptic receptors located on axon terminals, adopts the strength of transmission to a given situation. This will not only influence the function of the neurons system in health and disease, but also therapeutic and untoward effects of drugs that bind these nonsynaptic receptors and transporters (Vizi, 2000).


A triptycene-based approach to solubilising carbon nanotubes and C60.
We describe herein the synthesis of a triptycene-based surfactant designed with the ability to solubilise single-walled carbon nanotubes (SWNTs) and C(60) in water through non-covalent interactions. Furthermore, an amphiphilic naphthalene-based surfactant with the same ability to solubilise SWNTs and C(60) has also been prepared. The compounds synthesised were designed with either two ionic or non-ionic tails to ensure a large number of supramolecular interactions with the solvent, thereby promoting strong solubilisation. The surfactants produced stable suspensions in which the SWNTs are dispersed and the surfactant/SWNT complexes formed are stable for more than one year. UV/Vis/NIR absorption spectroscopy, TEM and AFM were employed to probe the solubilisation properties of the dispersion of surfactants and SWNTs in water.


Learning kernels from biological networks by maximizing entropy.
The diffusion kernel is a general method for computing pairwise distances among all nodes in a graph, based on the sum of weighted paths between each pair of nodes. This technique has been used successfully, in conjunction with kernel-based learning methods, to draw inferences from several types of biological networks. We show that computing the diffusion kernel is equivalent to maximizing the von Neumann entropy, subject to a global constraint on the sum of the Euclidean distances between nodes. This global constraint allows for high variance in the pairwise distances. Accordingly, we propose an alternative, locally constrained diffusion kernel, and we demonstrate that the resulting kernel allows for more accurate support vector machine prediction of protein functional classifications from metabolic and protein-protein interaction networks. Supplementary results and data are available at noble.gs.washington.edu/proj/maxent


Acetylcholine receptors, between closed and open.
Muscle acetylcholine receptors switch between conformations that either allow ('open') or prohibit ('closed') ion permeation. We probed the dynamics of this structural transition using linear free-energy relationships. Specific regions of the protein were perturbed (mutations, voltage or agonists) and the opening and closing rate constants were estimated from single-channel currents. Usually, a log-log plot of rate constant versus equilibrium constant was linear, with the slope indicating the sensitivity of the transition state to the perturbation as being between that of the open and closed conformation. The spatial gradient in this slope, from open-like at the transmitter binding sites to closed-like at the middle of the membrane, suggests that gating is a wave that propagates between the binding sites and the membrane domain.


Retrograde cardioplegia infusion during coronary bypass surgery. Early clinical experience.
Although aortic root cardioplegia infusion has been generally satisfactory, adequate myocardial protection in patients with critical coronary artery disease (CAD) cannot always be achieved by this route. We report our experience with our first 19 consecutive patients, all with exceptionally severe disease in whom the coronary sinus route was utilized for cardioplegia infusion. Eleven had unstable angina, and three had persistent chest pain requiring intensive antianginal therapy right up to time of surgery. Blood cardioplegia was infused via the coronary sinus using a Foley Catheter under a monitored pressure of 30 mmHg. Ischemic time was 83 +/- 27 minutes. Number of vessels bypassed was 4.9 +/- 0.9. Prebypass hemodynamic profile was compared to the profile at 15 and 75 minutes, and at 6, 12 and 24 hours after cessation of bypass, and revealed good preservation of myocardial function: Cardiac index, stroke volume index and pulmonary capillary wedge pressure remained unchanged, systemic vascular resistance decreased by 30%, while changes of lesser magnitude were observed in systemic and pulmonary blood pressure. There was no death and one perioperative myocardial infarction. Myocardial temperature was monitored by needle thermisters and demonstrated homogeneous myocardial cooling in spite of the severity of CAD. Thus, preservation of cardiac function even in patients with critical and extensive CAD can be achieved by coronary sinus infusion of cardioplegia.


Fibroepithelial Lesions in the Breast of Adolescent Females: A Clinicopathological Study of 54 Cases.
Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Forty-eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0-6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.


Comparison of endotracheal tube cuff pressure values before and after training seminar.
It is recommended that endotracheal cuff (ETTc) pressure be between 20 and 30 cm H2O. In this present study, we intend to observe average cuff pressure values in our clinic and the change in these values after the training seminar. The cuff pressure values of 200 patients intubated following general anesthesia induction in the operating theatre were measured following intubation. One hundred patients whose values were measured before the training seminar held for all physician assistants, and 100 patients whose values were measured after the training seminar were regarded as Group 1 and Group 2, respectively. Cuff pressures of both groups were recorded, and the difference between them was shown. Moreover, cuff pressure values were explored according to the working period of the physician assistants. There was no significant difference between the groups in terms of age, gender and tube diameters. Statistically significant difference was found between cuff pressure values before and after the training (p < 0.001). Average pressure measure for Group I was 54 cm H2O, while average pressure in Group II declined to 33 cm H2O. It was observed that as the working period and experience of physician assistants increased, cuff pressure values decreased, however no statistically significant different was found (p < 0.375). We believe that clinical experience does not have significant effects on cuff pressure and that training seminars held at intervals would prevent high cuff pressure values and potential complications.


Neonatal transfusion review.
In addition to the issues concerning blood transfusions in general, special considerations apply to transfusing neonates. Young infants' plasma may contain maternal antibodies to ABO blood group antigens instead of the naturally occurring anti-ABO antibodies normally present in older patients. This facilitates the transplant of hearts across ABO boundaries but complicates blood bank testing and selection of appropriate blood components for transfusion. Conversely, blood bank testing is simplified by the fact that neonates do not make antibodies to minor erythrocyte antigens. Cellular blood components may be irradiated to prevent transfusion-associated graft-versus-host disease, a syndrome that can affect immunocompromised patients such as premature infants. However, irradiation accelerates the leakage of potassium out of stored red blood cells (RBCs), increasing the risk or transfusion-induced arrhythmias from hyperkalemia and hypocalcemia. Two other risks of transfusing neonates RBCs include dilutional coagulopathy and potential toxicities from additives used to preserve the stored RBC units.


[Cementing techniques in hip arthroplasty: an overview].
For decades the cemented anchorage of hip prostheses, especially for elderly patients, is the standard procedure. The cementing technique has turned out to be the determining factor for the survival of the implant. In the last few years developments in this field have been able to further improve the long-term survival. Established components of the modern cementing technique are vacuum-mixed cements, medullary canal plugs, centralising elements und the use of jet-lavages. The design of the cemented shaft depends on the more important surface finish. In the most clinical studies, polished shafts turned out to be slightly superior as compared to shafts with rough surfaces.


Estrogen receptors by immunofluorescence: comparison with a dextran coated charcoal technique.
Biopsy specimens from 21 women with primary operable breast cancer were analyzed in a double blind study designed to compare fluorescent antibody methods for detection of estrogen receptors with estrogen receptors measured biochemically with a previously reported dextran coated charcoal technique (DCC). Fluorescent antibody methoids employed both direct techniques: (1) rabbit antisera to 6-O-Carboxymethyl-Oxime-17 beta Estradiol tagged with Fluorescin Istthiocyanate (FITC) and (2) indirect techniques (sheep antisera to 11-Hemisuccinate-17 beta Estradiol reacted wih FITC tagged rabbit antisheep sera). Fluorescent antibody methods showed 100 percent correlation with each other but only 67 percent correlation with the DCC assay. Fluorescence was striking when present. Molecular forms were not easily predicted. Divergent results occurred largely in specimes sparsely populated with malignant cells (18 percent) though neoplasms showing no fluorescence demonstrated elevated receptor conconcentrations with DCC (15 percent). Indirect fluorescent techniques are the simplest of those studied. Fluorescent techniques have not replaced biochemical techniques in the authors' laboratories.


Obeticholic Acid: A New Era in the Treatment of Nonalcoholic Fatty Liver Disease.
The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism. NAFLD has been proven to be associated with abnormal FXR activity. Obeticholic acid (OCA) is a first-in-class selective FXR agonist with anticholestatic and hepato-protective properties. Currently, OCA is registered for the treatment of primary biliary cholangitis. However, promising effects of OCA on NASH and its metabolic features have been reported in several studies.


Complex transcription from the extrachromosomal DNA encoding mitochondrial functions of Plasmodium yoelii.
All tested members of genus Plasmodium contain tandemly arrayed, transcribed, extrachromosomal DNA with a unit length of 6.0 kb. This DNA contains two open reading frames with potential to encode cytochrome c oxidase subunit I (cox1) and cytochrome b (cob) as well as fragments of rRNA genes scattered on both strands. At least 10 discrete RNA molecules transcribed during erythrocytic stages of a rodent malarial parasite, Plasmodium yoelii, were recognized by the 6.0-kb DNA probes. The RNA molecules of 1.4 and 1.1 kb were identified as encoding cox1 and cob, respectively. Primer extension and RNA sequencing were used to locate and characterize 5' ends of these two RNAs, showing that an identical 12-nucleotide sequence, 5'-TATTTTT TGTTT-3', was present at these positions. This sequence may act as a promoter or as an RNA processing signal. A stem-loop structure signifying a possible transcription termination was present at the end of the cox1 open reading frame. At least six discrete RNA molecules of less than 250 nucleotides were recognized by different fractions of the 6.0-kb DNA. The largest of these, 200 nucleotides, was also characterized by primer extension and RNA sequencing. This molecule had a high homology to portions of the large-subunit rRNA domains IV and V. Other, small RNA molecules were recognized by regions of the 6.0-kb DNA that had homology to the highly conserved peptidyltransferase domain of large-subunit rRNA. These results show that the unusual compactly organized mitochondrionlike DNA of malarial parasites is transcribed in a complex pattern.


Small intestinal submucosa intracardiac patch: an experimental study.
In this experimental study, small intestinal submucosa was implanted as an atrial prosthesis in calves. Echocardiography and histology showed this to be an impermeable prosthesis that develops a neointimal nonthrombogenic surface making it safe for repair of defects in a low-pressure system. Further study with small intestinal submucosa in an intracardiac position is warranted.


New concepts in prolactin biology.
Human prolactin (PRL) is currently viewed as a hormone of pituitary origin, whose production (i.e. serum levels) is controlled by dopamine, whose biological actions relate exclusively to lactation and reproductive functions, for which any genetic disorder is yet to be identified, and whose unique associated pathology is hyperprolactinemia. Both experimental studies and human sample/cohort-based investigations performed during the past decade have considerably widened our perception of PRL biology: i) there are now strong epidemiological arguments supporting the fact that circulating PRL is a risk factor for breast cancer, ii) in addition to the endocrine hormone, locally produced PRL has been documented in several human tissues; there is increasing evidence supporting the tumor growth potency of local PRL, acting via autocrine/paracrine mechanisms, in both rodent models, and human breast and prostate tumors, iii) the first functional germinal polymorphisms of the PRL receptor were recently identified in patients presenting with breast tumors, which involve single amino acid substitution variants exhibiting constitutive activity, iv) human PRL analogs have been engineered, which were shown in experimental models to down-regulate the effects triggered by local PRL (competitive antagonism) or by the constitutively active receptor variants (inverse agonism). The aim of this review is to discuss these novel concepts in PRL biology, including their potential pathophysiological outcomes.


Isolation and identification of sea buckthorn (Hippophae rhamnoides) phenolics with antioxidant activity and α-glucosidase inhibitory effect.
This study was performed to evaluate the antioxidant and α-glucosidase inhibitory effects from the extract, fractions, and isolated compounds of sea buckthorn leaves. Six compounds, kaempferol-3-O-β-D-(6''-O-coumaryl) glycoside, 1-feruloyl-β-D-glucopyranoside, isorhamnetin-3-O-glucoside, quercetin 3-O-β-D-glucopyranoside, quercetin 3-O-β-D-glucopyranosyl-7-O-α-L-rhamnopyranoside, and isorhamnetin-3-O-rutinoside, were isolated from sea buckthorn leaf extracts. The butanol fraction (EC(50) = 1.81 μg/mL) along with quercetin 3-O-β-D-glucopyranoside (EC(50) = 1.86 μg/mL) had a higher DPPH radical-scavenging activity and showed stronger reducing power (OD(700) = 1.83 and 1.78, respectively). The butanol fraction (477 mg GAE/g) contained the highest amount of phenolic compounds and also the most powerful α-glucosidase inhibitory effect (86%) at 5 μg/mL. The results indicate that sea buckthorn leaf extracts could potentially be used for food additives and the development of useful natural compounds.


Effect of anti-HIV 2'-beta-fluoro-2',3'-dideoxynucleoside analogs on the cellular content of mitochondrial DNA and on lactate production.
Many dideoxynucleosides that are effective against human immunodeficiency virus (HIV) also are potent inhibitors of mitochondrial DNA (mtDNA) synthesis, and the resulting mtDNA decrease could be responsible for the delayed clinical toxicity sometimes observed with these drugs. The following compounds have been examined for their toxicity to human lymphoid CEM cells, and their ability to suppress mtDNA content: 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyadenosine (ddA), 2',3'-dideoxyinosine (ddI) and 2',3'-dideoxyguanosine (ddG); and their 2'-beta-fluoro analogs; beta-F-ddC, beta-F-ddA, beta-F-ddI and beta-F-ddG. Two other fluoro analogs, 5-F-ddC and 2'-beta,5-di-F-ddC were also examined. The ratio of C-IC50 (concentration that inhibited cell growth by 50%) to mt-IC50 (concentration that inhibited mtDNA synthesis by 50%) was determined for each compound. The rank-order of this ratio was ddC > 5-F-ddC >> ddA > ddI > ddG > beta-F-ddC > beta-F-ddA > beta-F-ddG with the highest ratios indicating the greatest potential for delayed toxicity. In comparison with ddC, beta-F-ddC and beta-F-ddA were 5,000 and 22,000 times less potent, respectively, in suppressing cellular mtDNA content, while their anti-HIV potencies were decreased only modestly relative to their unfluorinated parent compounds. beta-F-ddI and 2'-beta,5-di-F-ddC produced neither cellular toxicity nor mtDNA suppression at concentrations of 500 and 1000 microM, respectively. Lactic acid, the product of compensatory glycolysis that results from the inhibition of mitochondrial oxidative phosphorylation, was measured after cells were treated with these compounds. There appears to be a concentration-related correlation between the increase of lactic acid and the extent of mtDNA inhibition for the compounds examined.


(-)-Epicatechin protects thoracic aortic perivascular adipose tissue from whitening in high-fat fed mice.
High adipose tissue (AT) accumulation in the body increases the risk for many metabolic and chronic diseases. This work investigated the capacity of the flavonoid (-)-epicatechin to prevent undesirable modifications of AT in mice fed a high-fat diet. Studies were focused on thoracic aorta perivascular AT (taPVAT), which is involved in the control of blood vessel tone, among other functions. Male C57BL/6J mice were fed for 15 weeks a high-fat diet with or without added (-)-epicatechin (20 mg per kg body weight per d). In high-fat diet fed mice, (-)-epicatechin supplementation: (i) prevented the expansion of taPVAT, (ii) attenuated the whitening of taPVAT (according to the adipocyte morphology, diameter, and uncoupling-protein 1 (UCP-1) levels) and (iii) blunted the increase in plasma glucose and cholesterol. The observed taPVAT modifications were not associated with alterations in the aorta wall thickness, aorta tumor necrosis factor-alpha (TNF-α) and NADPH-oxidase 2 (NOX2) expression, and endothelial nitric oxide synthase (eNOS) phosphorylation levels. In summary, our results indicate (-)-epicatechin as a relevant bioactive protecting from the slow and silent development of metabolic and chronic diseases as they are associated with excessive fat intake.


Inhibitory Effects of Acetyloctadecadienediynoic Acid Isolated from Leaves of Dendropanax morbiferus on Viability and Self-Renewal Activity of Glioma Stem-Like Cells.
Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed ''stem-like features'' in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs.


Experimental folate and vitamin B12 deficiency does not alter bone quality in rats.
Hyperhomocysteinemia (HHCY) has been linked to fragility fractures and osteoporosis. Folate and vitamin B(12) deficiencies are among the main causes of HHCY. However, the impact of these vitamins on bone health has been poorly studied. This study analyzed the effect of folate and vitamin B(12) deficiency on bone in rats. We used two groups of rats: a control group (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10). VitDef animals were fed for 12 wk with a folate- and vitamin B(12)-free diet. Co animals received an equicaloric control diet. Tissue and plasma concentrations of homocysteine (HCY), S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM) were measured. Bone quality was assessed by biomechanical testing (maximum force of an axial compression test; F(max)), histomorphometry (bone area/total area; B.Ar./T.Ar.], and the measurement of biochemical bone turnover markers (osteocalcin, collagen I C-terminal cross-laps [CTX]). VitDef animals developed significant HHCY (Co versus VitDef: 6.8 +/- 2.7 versus 61.1 +/- 12.8 microM, p < 0.001) that was accompanied by a high plasma concentration of SAH (Co versus VitDef: 24.1 +/- 5.9 versus 86.4 +/- 44.3 nM, p < 0.001). However, bone tissue concentrations of HCY, SAH, and SAM were similar in the two groups. Fmax, B.Ar./T.Ar., OC, and CTX did not differ between VitDef and Co animals, indicating that bone quality was not affected. Folate and vitamin B(12) deficiency induces distinct HHCY but has no effect on bone health in otherwise healthy adult rats. The unchanged HCY metabolism in bone is the most probable explanation for the missing effect of the vitamin-free diet on bone.


Recombinant antibodies: from the laboratory to the clinic.
The development of recombinant antibodies has facilitated the exploitation of the Ab-Ag interaction specificity for targeted therapies. A fully human antibody, with custom integrated designs, can be obtained in one-third the time, compared to development of antibodies by hybridoma technology. Recombinant antibodies can be tailored for specific applications, "armed" with cytotoxic agents in a controllable fashion, and used for extracellular and intracellular targeting. Multitargeted and combination therapies are rapidly evolving for the treatment of cancer. Antibody therapeutics, costly to develop and produce, have proven beneficial in the clinic.


A new anti-mesothelin antibody targets selectively the membrane-associated form.
Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that shows promise as a target for antibody-directed cancer therapy. High levels of soluble forms of the antigen represent a barrier to directing therapy to cellular targets. The ability to develop antibodies that can selectively discriminate between membrane-bound and soluble conformations of a specific protein, and thus target only the membrane-associated antigen, is a substantive issue. We show that use of a tolerance protocol provides a route to such discrimination. Mice were tolerized with soluble mesothelin and a second round of immunizations was performed using mesothelin transfected P815 cells. RNA extracted from splenocytes was used in phage display to obtain mesothelin-specific antigen-binding fragments (Fabs) that were subsequently screened by flow cytometry and ELISA. This approach generated 147 different Fabs in 34 VH-CDR3 families. Utilizing competition assays with soluble protein and mesothelin-containing serum obtained from metastatic cancer patients, 10 of these 34 VH-CDR3 families were found to bind exclusively to the membrane-associated form of mesothelin. Epitope mapping performed for the 1H7 clone showed that it does not recognize GPI anchor. VH-CDR3 sequence analysis of all Fabs showed significant differences between Fabs selective for the membrane-associated form of the antigen and those that recognize both membrane bound and soluble forms. This work demonstrates the potential to generate an antibody specific to the membrane-bound form of mesothelin. 1H7 offers potential for therapeutic application against mesothelin-bearing tumors, which would be largely unaffected by the presence of the soluble antigen.


Allostatic load in opioid use disorder: a scoping review protocol.
Opioid use disorder affects 2.1 million individuals in the USA, causing more than 100 000 overdose-related deaths annually. While the neurobiological model of addiction is well described and accepted, there is a lack of morbidity and mortality prognosticators for patients struggling with opioid use disorder. Allostatic load index is a promising candidate for the basis of a prognostication tool. Previous studies show that allostatic load predicts both morbidity and mortality in a variety of cohorts. This scoping review protocol provides the rationale and steps for summarising and presenting existing evidence surrounding allostatic load in the context of opioid use disorder. Identification of current knowledge gaps will pave the way for subsequent prospective studies. This scoping review protocol will follow the five-step method designed by Arksey and O'Malley. All studies written in English on allostatic load in the context of opioid use disorder, as defined in our inclusion criteria, will be included. There will be no limit on the year of publication. We will search PubMed, Embase, CINAHL, PsycINFO and Google Scholar. We will hand-review reference lists of included articles, and we will hand search grey literature. We will then group, analyse and present the data in narrative, tabular and diagrammatic format according to themes identified in the scoping review. Ethics approval is not necessary, as data are gathered from publicly accessible sources. The results will be disseminated through a peer-reviewed journal and reported at conferences related to addiction medicine. 10.17605/OSF.IO/4J6DQ.


Specificity and time-course of attentional bias in chronic headache: a visual-probe investigation.
The specificity and time-course of attentional bias in chronic headache were investigated. Individuals with chronic headache, compared with healthy controls, were hypothesized to show significant attentional bias towards disorder-relevant headache-related images. Individuals with chronic headache (n=37) and headache-free controls (n=38) completed a visual-probe task with headache-related, pain-related, health-threat, and general-threat pictorial stimuli, which were presented at 500 and 1250 ms exposure durations. Individuals with chronic headache, compared with headache-free controls, demonstrated significant bias towards headache-related images presented for 1250 ms. Considering participant groups separately, the chronic headache group showed bias towards headache-related images at 500 and 1250 ms, and pain-related images at 500 ms. The control group showed bias towards general-threat images at 500 ms. Individuals with chronic headache demonstrate attentional bias towards pain information, which is most prominently shown towards stimuli relevant to their specific disorder. Biases are also more pronounced at longer stimuli presentation times associated with maintained attention. Future research should investigate the clinical implications of attentional bias in chronic headache, and further explore the benefits of attentional bias modification upon patient functioning.


Chief Executive Officer Tenacity and Employee Intrapreneurial Behavior: The Mediating Role of Corporate Social Responsibility.
Chief executive officer (CEO) tenacity plays an important role in corporate entrepreneurial activity. However, much less is known about its impact on employee intrapreneurship. Drawing from social information processing theory and upper echelons theory, this article examines the hitherto unexplored nexus between CEO tenacity and employee intrapreneurship, as well as the mediating role of corporate social responsibility (CSR). Quantitative data were collected through a survey administered to 294 employees working in different sectors that engage in CSR activities in China. Data analysis was performed using hierarchical regression method through Stata 16.0. It was found that CEO tenacity was significantly positively correlated with employee strategic renewal behavior (β = 0.523, p < 0.001) and employee venture behavior (β = 0.510, p < 0.001). The positive correlation between CEO tenacity and CSR was also significant (β = 0.578, p < 0.001). Besides, CSR partially mediated the relationship between CEO tenacity and employee strategic renewal behavior (40.0%) or employee venture behavior (50.2%). This study extends research on CEO tenacity, CSR, or employee intrapreneurial behavior by providing a better understanding of the direct effects of CEO tenacity on employee intrapreneurial behavior and CSR. From the perspective of cross-fertilization between psychology and management, this study establishes the interface role of CSR by elucidating the intrinsic mechanism of CEOs with high levels of tenacity to stimulate employee intrapreneurial behavior through CSR.


Robustness of ancestral sequence reconstruction to phylogenetic uncertainty.
Ancestral sequence reconstruction (ASR) is widely used to formulate and test hypotheses about the sequences, functions, and structures of ancient genes. Ancestral sequences are usually inferred from an alignment of extant sequences using a maximum likelihood (ML) phylogenetic algorithm, which calculates the most likely ancestral sequence assuming a probabilistic model of sequence evolution and a specific phylogeny--typically the tree with the ML. The true phylogeny is seldom known with certainty, however. ML methods ignore this uncertainty, whereas Bayesian methods incorporate it by integrating the likelihood of each ancestral state over a distribution of possible trees. It is not known whether Bayesian approaches to phylogenetic uncertainty improve the accuracy of inferred ancestral sequences. Here, we use simulation-based experiments under both simplified and empirically derived conditions to compare the accuracy of ASR carried out using ML and Bayesian approaches. We show that incorporating phylogenetic uncertainty by integrating over topologies very rarely changes the inferred ancestral state and does not improve the accuracy of the reconstructed ancestral sequence. Ancestral state reconstructions are robust to uncertainty about the underlying tree because the conditions that produce phylogenetic uncertainty also make the ancestral state identical across plausible trees; conversely, the conditions under which different phylogenies yield different inferred ancestral states produce little or no ambiguity about the true phylogeny. Our results suggest that ML can produce accurate ASRs, even in the face of phylogenetic uncertainty. Using Bayesian integration to incorporate this uncertainty is neither necessary nor beneficial.


Wood-Ljungdahl pathway found in novel marine Korarchaeota groups illuminates their evolutionary history.
Korarchaeota, due to its rarity in common environments, is one of the archaeal phyla that has received the least attention from researchers. It was previously thought to consist solely of strict thermophiles. However, our study provides genetic evidence for the presence of korarchaeal members in temperate subsurface seawater. Furthermore, a systematic reclassification of the Korarchaeota based on 16S rRNA genes and genomes has revealed three novel marine groups (Kor-6 to Kor-8) at the root of the Korarchaeota branch. Kor-6 contains microbes that are present in moderate temperatures. All three novel marine phyla possess genes for the Wood-Ljungdahl pathway, and Kor-7 and Kor-8 possess fewer genes encoding oxygen resistance traits than other korarchaeal groups, suggesting a distinct lifestyle for these novel phyla. Our results, together with estimations of Korarchaeota divergence times, suggest that oxygen availability may be one of the important factors that have influenced the evolution of Korarchaeota. IMPORTANCE Korarchaeota were previously thought to inhabit exclusively high-temperature environments. However, our study provides genetic evidence for their unexpected presence in temperate marine waters. Through analysis of publicly available korarchaeal reference data, we have systematically reclassified Korarchaeota and identified the existence of three previously unknown marine groups (Kor-6, Kor-7, and Kor-8) at the root of the Korarchaeota branch. Comparative analysis of their gene content revealed that these novel groups exhibit a lifestyle distinct from other Korarchaeota. Specifically, they have the ability to fix carbon exclusively via the Wood-Ljungdahl (WL) pathway, and the genomes within Kor-7 and Kor-8 contain few genes encoding antioxidant enzymes, indicating their strictly anaerobic lifestyle. Further studies suggest that the genes related to methane metabolism and the WL pathway may have been inherited from a common ancestor of the Korarchaeota and that oxygen availability may be one of the important evolutionary factors that shaped the diversification of this archaeal phylum.


Serum pyridoxal in patients with rheumatoid arthritis.
Abnormalities of tryptophan metabolism have been reported in patients with rheumatoid arthritis (RA) and it has been suggested that these abnormalities are the result of disordered vitamin B6 metabolism. Fasting serum pyridoxal, assayed by an automated microbiological system, was found to be below normal in 35 out of 42 patients with RA while a similar abnormality was found in 8 out of 35 patients with osteoarthrosis (OA). Within the RA group the abnormality could not be related to the age, sex, or drug therapy of individuals but of the 8 patients with OA and a low serum pyridoxal, 7 were receiving indomethacin either alone or in conjunction with aspirin.


Seroprevalence and isolation of Toxoplasma gondii from sheep from São Paulo state, Brazil.
Sheep are important in the epidemiology of Toxoplasma gondii infection but little is known of ovine toxoplasmosis in Brazil. Antibodies to T. gondii were assayed in sera of 495 sheep from 36 counties of São Paulo State, Brazil, using the modified agglutination test (MAT titer > or =1:25) and found in 120 (24.2%). Samples of brain, heart, and diaphragm of 82 seropositive sheep were pooled, digested in pepsin, and bioassayed in mice. Toxoplasma gondii was isolated from tissue homogenates of 16 sheep and the isolates were designated TgShBr1-16. Six of the 16 T. gondii isolates killed 100% of infected mice. Results indicate that asymptomatic sheep can harbor mouse-virulent T. gondii, and hence they can serve as a source of infection for humans.


Stimuli-responsive nanozymes for biomedical applications.
With the rapid development of nanotechnology, nanozymes are regarded as excellent substitutes for natural enzymes due to their high activity, convenient preparation, low cost, robust stability and other unique properties of nanomaterials. In biomedical applications, the always-on activity of nanozymes is undesirable as it poses a potential threat to normal tissues. Stimuli-responsive nanozymes were designed to manipulate the activities of nanozymes. This review introduces two types of stimuli-responsive nanozymes. One is smart responsive nanozymes with stimuli-switchable activities, further divided into those with on/off switchable activity and one/another switchable activity. Another is nanozymes exhibiting responsive release from specific carriers. Additionally, the biomedical applications of stimuli-responsive nanozymes in cancer therapy, antibacterial therapy, biosensing and anti-inflammatory therapy are briefly reviewed. Finally, we address the challenges and prospects in this field.


A case of manifesting carrier with DMD phenotype.
A case of a 35-year old female with a history of proximal weakness in lower limbs and bulkiness of both calves manifesting before ten years of age was reported. Clinical findings were suggestive of muscular dystrophy. Genetic analysis using polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) and direct sequencing revealed several point mutations, which account for dystrophin dysfunction and DMD type pathogenesis.


Mitochondrial Reactive Oxygen Species and Lytic Programmed Cell Death in Acute Inflammation.
Significance: Redox signaling through mitochondrial reactive oxygen species (mtROS) has a key role in several mechanisms of regulated cell death (RCD), necroptosis, ferroptosis, pyroptosis, and apoptosis, thereby decisively contributing to inflammatory disorders. The role of mtROS in apoptosis has been extensively addressed, but their involvement in necrotic-like RCD has just started being elucidated, providing novel insights into the pathophysiology of acute inflammation. Recent Advances: p53 together with mtROS drive necroptosis in acute inflammation through downregulation of sulfiredoxin and peroxiredoxin 3. Mitochondrial hydroorotate dehydrogenase is a key redox system in the regulation of ferroptosis. In addition, a noncanonical pathway, which generates mtROS through the Ragulator-Rag complex and acts via mTORC1 to promote gasdermin D oligomerization, triggers pyroptosis. Critical Issues: mtROS trigger positive feedback loops leading to lytic RCD in conjunction with the necrosome, the inflammasome, glutathione depletion, and glutathione peroxidase 4 deficiency. Future Directions: The precise mechanism of membrane rupture in ferroptosis and the contribution of mtROS to ferroptosis in inflammatory disorders are still unclear, which will need further research. Mitochondrial antioxidants may provide promising therapeutic approaches toward acute inflammatory disorders. However, establishing doses and windows of action will be required to optimize their therapeutic potential, and to avoid potential adverse side effects linked to the blockade of beneficial mtROS adaptive signaling. Antioxid. Redox Signal. 39, 708-727.


[Poliomyelitis surveillance in the Czech Republic from the start of vaccination to the certification of eradication in the European Region].
Poliomyelitis anterior acuta is an acute infectious disease caused by polioviruses of three antigenic types. First epidemics of poliomyelitis emerged at the end of the 19th century. The World Health Organization launched the poliomyelitis eradication program in 1988. The incidence of poliomyelitis in the world decreased from 350,000 cases in 1988 to 1918 cases in 2002 when poliomyelitis eradication was certified in three WHO regions, the European Region (2002), American Region (1994) and West Pacific Region (2000). Systematic clinico-virological surveillance of poliomyelitis has been carried in the Czech Republic since 1961, including annual vaccination campaigns with living OPV vaccine, clinical screening, virological screening of clinical specimens and sewage water (environmental) samples and sera screening within serological surveys mapping the vaccination immunological efficacy. From 1961 to 2003, 21,423 stool specimens of vaccinated healthy children, 62,440 stool specimens of patients, 6250 cerebrospinal fluid specimens and 2100 throat swab specimens were screened. Within the outdoor environment surveillance, 15,460 sewage water samples were analysed. From 1995 to 2003 129 cases of acute flaccid paresis were investigated in children under 15 years of age and 28 stool samples from their contacts were screened. Over the same period, 1280 sewage water samples from refugee camps were analysed. For serological surveys, about 60,000 sera from healthy individuals of all age categories were investigated. No case of paralytic poliomyelitis has been reported and no wild virus has been isolated in the Czech Republic since 1961.


The long-acting dopamine agonist bromocriptine mesylate as additive immunosuppressive drug after kidney transplantation.
Acute rejection is an important risk factor for kidney graft loss. As evidence suggests that prolactin has important immunostimulatory properties, we conducted a randomized, prospective open trial in which bromocriptine, a drug suppressing prolactin secretion, was administered as an additive immunosuppressive drug after first cadaver kidney transplantation. In the treatment group bromocriptine was given intramuscularly to 22 patients after their first kidney transplantation along with conventional immunosuppression (cyclosporin A, glucocorticoids). Twenty-three patients receiving only conventional immunosuppression served as control subjects. The incidence of acute graft rejections, graft losses, and infections was evaluated. Serum prolactin concentrations were slightly elevated above normal values before transplantation (32 +/- 5.3 ng/ml) and decreased to values between 13 and 16 ng/ml in the control group and were totally suppressed in the bromocriptine group. After 6 months of follow-up overall patient and allograft survival was 97.7% and 91% respectively. Acute rejection episodes occurred in 31 patients (77.5%): 15 in the bromocriptine group vs 20 in the control group (n.s.). In each group eight patients experienced a cytomegalovirus infection. The incidence of severe bacterial infections (i.e. pneumonia and sepsis) was five and six respectively. The necessity of haemodialysis after transplantation was 3.1% in the patients on bromocriptine and 23% in those without. Suppression of circulating prolactin concentration by bromocriptine did not improve the clinical outcome of patients after kidney transplantation receiving cyclosporin and prednisolone.


Preschoolers' genetic, physiological, and behavioral sensitivity factors moderate links between parenting stress and child internalizing, externalizing, and sleep problems.
This study examined three potential moderators of the relations between maternal parenting stress and preschoolers' adjustment problems: a genetic polymorphism-the short allele of the serotonin transporter (5-HTTLPR, ss/sl allele) gene, a physiological indicator-children's baseline respiratory sinus arrhythmia (RSA), and a behavioral indicator-mothers' reports of children's negative emotionality. A total of 108 mothers (Mage = 30.68 years, SDage = 6.06) reported on their parenting stress as well as their preschoolers' (Mage = 3.50 years, SDage = 0.51, 61% boys) negative emotionality and internalizing, externalizing, and sleep problems. Results indicated that the genetic sensitivity variable functioned according to a differential susceptibility model; however, the results involving physiological and behavioral sensitivity factors were most consistent with a diathesis-stress framework. Implications for prevention and intervention efforts to counter the effects of parenting stress are discussed.


[TREATMENT OUTCOMES OF BLADDER NECK CONTRACTURE AFTER TRANSURETHRAL PROSTATE SURGERY].
(Introduction) A known complication of the surgical treatment of benign prostatic hyperplasia (BPH) is bladder neck contracture (BNC). BNC is often treated using transurethral incision of the bladder neck (TUI-BN); however, there are few reports on the outcomes of TUI-BN. Therefore, we examined the outcomes of patients who underwent TUI-BN after transurethral prostate surgery. (Material and methods) We retrospectively examined 25 patients who underwent TUI-BN between February 2015 and January 2021 for the following: (1) patients' characteristics; (2) the time from transurethral prostate surgery to TUI-BN; (3) the trigger of BNC diagnosis; (4) surgical procedure of BNC repair/perioperative course; (5) micturition function immediately after TUI-BN; and (6) Postoperative outcomes. (Results) The median age of the patients was 77 years, and the surgical procedures for BPH were transurethral resection of the prostate (TURP) in four cases, transurethral resection in saline plasma vaporization of the prostate (TURisP) in nine cases, and transurethral enucleation with bipolar (TUEB) in 12 cases. The median time to onset of BNC symptoms was 364 days, and 18 patients (72%) were diagnosed within 2 years. The trigger of BNC diagnosis was urinary symptoms in 21 cases, of which 16 patients had exacerbation of urination. The median duration of the surgical procedure of BNC repair was 14 min, and the incisions most frequently used (in 44% of cases) were at the 4 o'clock and 8 o'clock positions. Transient stress urinary incontinence was observed as a complication in three cases. In the 4 o'clock and 8 o'clock incisions, the maximum urine flow rate improved significantly (11.1 mL/s perioperatively vs. 20.9 mL/s postoperatively; P=0.004). These symptoms improved in 16 of the 21 symptomatic cases, and the maximum urine flow rate improved significantly (P< 0.01). The median observation period after surgery was 170 days; eight postoperative patients were lost to follow up. There were two cases of recurrence. (Conclusions) BNC is likely to develop within 2 years after transurethral prostate surgery. In this study, the success rate of the initial TUI-BN was 92%, as reoperation was required in two cases; however, the overall prognosis was good.


Epitope patterns of anti-RNP antibodies in rheumatic diseases. Evidence for an antigen-driven autoimmune response.
Autoantibodies against small nuclear ribonucleoproteins (snRNP) are common in systemic lupus erythematosus and related disorders. The 3 categories, anti-(U1)RNP, anti-(U1, U2)RNP, and anti-Sm, all contain a common antibody specificity directed against the U1 snRNP-associated A protein. To determine the specificity of anti-U1 snRNP A protein antibodies for various antigenic sites, we tested 26 different anti-snRNP-positive sera for reactivity with fragments of the U1 snRNP A protein, which was produced using recombinant DNA technology. Several different fragments were shown to contain autoimmune-reactive epitopes, which indicates that the antibody response against the U1 snRNP A protein is polyclonal. Antibodies against a discontinuous or conformational epitope were found in most of the sera tested, regardless of whether they were classified as anti-(U1)RNP, anti-Sm, or anti-(U1, U2) RNP. These results strongly support the hypothesis that the anti-snRNP autoimmune response is antigen driven.


[The epidemiology of bloodstream infections in Fuxing Hospital in 2012 in Beijing].
To investigate the etiology, clinical features and outcome of hospitalized patients with bloodstream infections (BSIs) in a tertiary hospital. Positive blood cultures were obtained from the microbiological laboratory in Fuxing Hospital, Capital Medical University from January 1, 2012 to December 31, 2012. BSIS events were identified and the epidemiology data were collected. A total of 149 patients and 154 BSIs events were confirmed by pathogenic and clinical evidence. The in-patients' BSIs rate was 0.8% in our hospital in 2012. According to the disease entities of the first BSIs onset, 15 patients (10.1%) were from surgical departments, 83 patients (55.7%) from the medical departments, and 51 patients (34.2%) from ICU. Thirty-three patients (22.1%) were diagnosed as septic shock. Sixty-eight patients died during hospital stay. The in-hospital mortality rate was 45.6%. Among the 154 BSIs events, 125 (81.2%) were nosocomial and 29 (18.8%) were community-acquired. A total of 188 strains were isolated from all BSIs, including 106 strains of (56.4%) gram-negative bacilli, 67 (35.6%) strains of gram-positive bacteria, and 15 (8.0%) strains of fungi. One hundred and fifty-nine strains of bacteria (84.6%)were isolated from 125 events of hospital-acquired BSIs. Twenty-six strains of bacteria were from catheter related bloodstream infections (CRBSIs). In gram-negative BSIs, there were more enterobacteriaceae in community-acquired BSIs. More non-fermentative bacteria were found in hospital-acquired BSIs than in community-acquired ones. The distribution of gram-negative bacilli was quite different between surgical departments, non-surgical departments and ICU (P=0.049). Pathogens of BSIs are quite different according to disease entities and where the patients are from. Local epidemiology of BSIs and distribution of related pathogens are helpful to physicians searching the optimal empirical antibiotics and improving the outcome.


Nephrocan, a novel member of the small leucine-rich repeat protein family, is an inhibitor of transforming growth factor-beta signaling.
In a search of new, small leucine-rich repeat proteoglycan/protein (SLRP) family members, a novel gene, nephrocan (NPN), has been identified. The gene consists of three exons, and based on the deduced amino acid sequence, NPN has 17 leucine-rich repeat motifs and unique cysteine-rich clusters both in the N and C termini, indicating that this gene belongs to a new class of SLRP family. NPN mRNA was predominantly expressed in kidney in adult mice, and during mouse embryogenesis, the expression was markedly increased in 11-day-old embryos at a time when early kidney development takes place. In the adult mouse kidney, NPN protein was located in distal tubules and collecting ducts. When NPN was overexpressed in cell culture, the protein was detected in the cultured medium, and upon treatment with N-glycosidase F, the molecular mass was lowered by approximately 14 kDa, indicating that NPN is a secreted N-glycosylated protein. Furthermore, transforming growth factor-beta (TGF-beta)-responsive 3TP promoter luciferase activity was down-regulated, and TGF-beta-induced Smad3 phosphorylation was also inhibited by NPN, suggesting that NPN suppresses TGF-beta/Smad signaling. Taken together, NPN is a novel member of the SLRP family that may play important roles in kidney development and pathophysiology by functioning as an endogenous inhibitor of TGF-beta signaling.


Effect of leptin receptor Q223R polymorphism on breast cancer risk.
Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.


MCP-1-2518 (A>G) polymorphism and asthma risk: a pilot case-control study in Cameroon.
there is little data on the genetic determinants of asthma in Cameroon and sub-Saharan Africa, yet the involvement of genetics in the pathogenesis of this disease has been reported in the literature for several years. This study aims to investigate the possible role of MCP-1 2518 for the risk of asthma in Cameroonians. we performed a case-control study on 30 volunteers suffering from asthma, matched by aged and sex to 30 healthy subjects. We determine the polymorphism of MCP-1 2518 using restriction fragment length polymorphism following Polymerase Chain Reaction (RFLP-PCR). Fisher exact test was used to compare proportions, with a threshold of significance set at 0.05. the average age of cases was 21±10 years with 17 (56.7%) females. The distribution of the MCP-1-2518 (A>G) gene polymorphism in people with asthma was as follows: 3 for AA, 5 for GG, and 22 for AG. The minor G allele was predominant (90%) in people with asthma. It was significantly associated with asthma whether the genotype was heterozygous AG or homozygous GG (p<0.01). MCP-1-2518 (A>G) shows an association with asthma in our sample. Future larger studies evaluating several polymorphisms are needed to describe the genetic determinants of asthma in Cameroon and sub-Saharan Africa.


Measurement of biological effects of high-energy carbon ions at low doses using a semi-automated cell detection system.
To study the effects of low-dose, high-LET irradiation in order to detect possible deviations from a linear-quadratic dose dependence. Experiments using charged particle irradiation were performed, in particular in the low-dose range from 0 to 2 Gy, and compared with experiments using photon radiation. The survival of V79 cells was studied by means of a semi-automated system, which allowed the detection and relocation of positions of individual cells at regular intervals. It consists of an inverted microscope equipped with a computerized stage control and image processing system. With such a technique, the precision of the survival assay is increased by avoiding the stochastic uncertainties of the conventional dilution assay. Furthermore, by means of daily observations, the system allows a detailed study of the growth kinetics of individual cells up to approximately 1 week after irradiation. Up to now, high-LET experiments have been performed using mainly 100 MeV/u carbon ions (LET: 28 keV/microm). A significant hypersensitivity at low doses (0.1 Gy) has been detected for these ions. It is the first report of such a pronounced effect for charged particle irradiation. Although hypersensitivity after carbon ion irradiation apparently is in contrast to other data reported for peak pion irradiation at similar LET values, the difference might possibly be due to differences in the track structure of the particles.


[Pulmonary edema and tocolysis with beta-agonists].
It is not unusual for respiratory specialists to be called to deal with respiratory problems in pregnancy. However, some conditions, such as tocolysis-induced pulmonary edema, although common, are largely unknown to our specialty. We report on the cases of three pregnant women, who developed pulmonary edema in the context of tocolysis with the intra-venous infusion of B-agonists. In all three patients, tocolysis was required because contraction developed well before term. Triple pregnancy was present in one patient. In another patient, mechanical ventilation was required. The outcome was good with full recovery in all three cases.


Urinary retinol excretion in children with acute watery diarrhoea.
Children with diarrhoea due to rotavirus infection excrete retinol in urine. This study aimed at demonstrating the extent and mechanism of urinary retinol excretion in children with acute watery diarrhoea caused by pathogens other than rotavirus. Thirty-two children, aged five months to five years, hospitalized with watery diarrhoea predominantly due to enterotoxigenic Escherichia coli in Bangladesh, were studied. Their serum retinol and retinol-binding protein (RBP) were low at admission and increased significantly after recovery from illness. The mean hospital stay of these patients was four days. Forty-seven percent of the children excreted retinol in urine on day 1, and about 38% continued excreting retinol on day 3. The estimated urinary retinol loss of 3.44 micromol for the illness episode represented more than 40% of liver retinol reserve (8.25 micromol) in malnourished children. A conservative estimate of the loss would represent at least 20% of the liver reserve in relatively better-nourished children. Kidney tubular dysfunctions of increased RBP excretion significantly predicted urinary retinol excretion in children with watery diarrhoea.


Simultaneous occurrence of adenomas in stomach, duodenal bulb, and colon: disappearance of gastric and duodenal adenomas during oral administration of 5'-deoxy-5-fluorouridine.
The present report concerns a patient who was first diagnosed as having adenoma in the duodenal bulb and subsequently was discovered to have adenomas in the stomach and colon. Surgical procedures including endoscopic resection could not be carried out because the patient had advanced liver cirrhosis. Follow-up colonoscopy no longer detected any polyp in the colon. Ultrasonography demonstrated a slowly growing hypoechoic mass in the liver, which was indicative of hepatocellular carcinoma. Then, single chemotherapy with oral administration of 5'-deoxy-5-fluorouridine was initiated. Surprisingly, repeated esophagogastroduodenoscopy revealed gradual regression of the gastric and duodenal tumors. Findings from the endoscopy and biopsy materials 10 months after the start of therapy showed disappearance of the gastric and duodenal adenomas. Despite enlargement of the hepatic mass, no recurrence of gastric and duodenal tumors has been noted during the past 1 1/2 yr.


Systematic comparison of tissue fixation with alternative fixatives to conventional tissue fixation with buffered formalin in a xenograft-based model.
In our study we systematically compared the alternative fixatives acidified formal alcohol (AFA), PAXgene®, HOPE®, and combinations of AFA or formalin with ultrasound treatment to standard (buffered) formalin fixation. We examined general morphology and detectability of protein structures by immunohistochemistry of the membrane receptors epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), and phosphorylated human epidermal growth factor receptor 2 (phospho-HER2). In order to allow for stringent comparability of different fixation techniques, we used matched mouse xenograft tumor samples from three different human cancer cell lines (colon, ovarian, and non-small cell lung cancer), either fixed conventionally with formalin or an alternative fixative. Tissue morphology after fixation with AFA and PAXgene® was comparable to formalin-fixed paraffin-embedded tissue (FFPET) morphology. Ultrasound fixations resulted in slightly inferior morphology and HOPE® fixation preserved morphology only poorly compared to FFPET in this system. None of the tested alternative fixatives enabled immunohistochemical detectability of all three targets in the same manner as FFPET. Pronounced staining was possible for EGFR and IGF-1R with all alternative fixatives but HOPE®, and phospho-HER2 staining was only noteworthy with formalin-ultrasound-fixed tissue. Therefore, the use of alternative fixatives comes with the need for careful validation of obtained IHC results individually for each target.


Rural mental health units--is there a role for a GP?
Mental illness is a common medical condition which is increasing in frequency. In Australia, almost one in five persons have experienced an anxiety, depressive or substance abuse disorder in the last 12 months, but less than half have sought professional assistance. In rural and remote areas, there is limited access to psychiatrists, and the majority of mental health care resides with the GP. This study aimed to ascertain the opinions of GPs in rural and remote areas of Queensland on the concept of locating a GP within in a mental health unit. Participants were all general practitioners listed on the databases of the Rural Divisions of General Practice covering RRMA 5-7 in Queensland, Australia, excluding those who could potentially refer patients to the mental health unit where the principal investigator worked. A specially designed questionnaire was forwarded to eligible GPs in a series of three mailings. In total, 145 GPs returned the questionnaire, giving a 69% response rate. The majority of GP respondents believed that there was a significant number of patients with mental illness who would benefit from the contribution of a GP, and that locating a GP within a mental health unit was a viable option, especially for enhancing continuity of care and consequently overall health. The majority of respondents said they felt confident in treating mental illness, especially those with higher mental health caseloads and those with a professional college fellowship. However, there were varying inclinations towards working in such a unit, with no definite preferred method of remuneration identified. Rural and remote GPs in Queensland believe there is a case for placing a GP within established mental health units, subject to addressing logistic and remuneration issues, as they believe this would enhance continuity of care and improve overall health for those with mental health problems.


Dual Influence of Reduction Annealing on Diffused Hematite/FTO Junction for Enhanced Photoelectrochemical Water Oxidation.
Band structure engineering of the interface between the semiconductor and the conductive substrate may profoundly influence charge separation and transport for photovoltaic and photoelectrochemical devices. In this work, we found that a reduction-annealing treatment resulted in a diffused junction through enhanced interdiffusion of hematite/FTO at the interface. The activated hematite exhibited higher nanoelectric conductivity that was probed by a PeakForce TUNA AFM method. Furthermore, charge accumulation and recombination via surface states at the interface were dramatically reduced after the reduction-annealing activation, which was confirmed by transient surface photovoltage measurements. The diffused hematite junction promises improved photoelectrochemical performance without the need for a buffer layer.


Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect.
Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.


[The cement free hollow hip prosthesis to reduce intramedullary pressure].
A hollow cementless femoral stem has been developed to reduce intramedullary pressure and fat embolism during implantation. In a prospective randomized clinical study, cementless hip stems (ALPHA-FIT) were implanted in 42 patients (24 women, 18 men, mean age: 65.9 years). In Group I (n=21) a solid standard stem was used. In Group II (n=21) a modified hollow stem was implanted with vertical and longitudinal communicating drill holes opening at the implant surface. During surgery the intramedullary pressure was measured by a cannula fixed distally. During stem insertion the mean pressure was 82 mmHg (minimum-maximum, 12-259 mmHg) for Group I and 27 mmHg (minimum-maximum, 0-48 mmHg) for Group II. This difference was statistically significant (t-test, p < 0.00076). The pressure measured in Group II was similar to the base pressure before opening of the intramedullary canal (mean 35 mmHg; minimum-maximum, 4-72 mmHg). In both groups higher pressures were found for opening of the canal, drilling with the smallest drill size and rasping. Using the hollow prosthesis, the intramedullary pressure could be reduced significantly. The higher pressures during preparation of the femoral canal need further research.


[Experimental animal study of cerebral oxygen metabolism changes during the process of brain death].
To reproduce a stable animal model of brain death in pigs, observe the change regularity of cerebral oxygen metabolism during the process of brain death, and to evaluate the significance and value of cerebral oxygen metabolism parameters for the diagnosis of brain death. Twelve landrace pigs were used to create the brain death models using modified method of increasing epidural intracranial pressure (ICP). The mean arterial pressure (MAP) and ICP were monitored continuously during the process. The pigs were divided into four groups according to cerebral perfusion pressure (CPP) decreasing degree during brain death, namely CPP normal group and CPP decreasing 0%-30%, 30%-70%, and 70%-100% groups. Blood gas analysis of the external carotid artery and internal jugular vein were monitored discontinuously. The changes in cerebral oxygen metabolism parameters, including external carotid artery-internal jugular vein bulb oxygen content difference (AJDO2), internal jugular bulb-external carotid artery carbon dioxide partial pressure difference (DPCO2) and DPCO2/AJDO2 ratio, were observed. Brain death model were successfully reproduced in 12 experimental pigs. With MAP and ICP monitoring, the models at different stages of CPP could be repeatedly induced. The levels of AJDO2 and DPCO2 were increased gradually and then decreased, while the ratio of DPCO2/AJDO2 was constantly increased with the decrease of CPP. The level of AJDO2 in CPP decreasing 0%-30% group was significantly higher than that in CPP normal group [(5.86±1.21)% vs. (3.92±0.64)%], the levels of DPCO2 in CPP decreasing 0%-30% and CPP decreasing 30%-70% groups were significantly higher than those in CPP normal group [mmHg (1 mmHg = 0.133 kPa): 10.33±1.83, 11.48±2.32 vs. 6.11±1.43], and the ratios of DPCO2/AJDO2 in CPP decreasing 30%-70% and CPP decreasing 70%-100% groups were significantly higher than those in CPP normal group and CPP decreasing 0%-30% group (2.81±0.53, 4.12±1.07 vs. 1.57±0.64, 1.62±0.81). All the differences above were statistically significant (all P < 0.05). With the decrease of CPP, cerebral oxygen metabolism showed a regular change during brain death. DPCO2 combined with DPCO2/AJDO2 is a reliable blood gas analysis index indicating intracranial hypoperfusion, which has certain reference value for the determination of brain death.