Possible evolutionary relationships between streptomycin and bluensomycin biosynthetic pathways: detection of novel inositol kinase and O-carbamoyltransferase activities.
Bluensomycin (glebomycin) is an aminocyclitol antibiotic that differs structurally from dihydrostreptomycin in having bluensidine (1D-1-O-carbamoyl-3-guanidinodeoxy-scyllo-inositol) rather than streptidine (1,3-diguanidino-1,3-dideoxy-scyllo-inositol) as its aminocyclitol moiety. Extracts of the bluensomycin producer Streptomyces hygroscopicus form glebosus ATCC 14607 (S. glebosus) were found to have aminodeoxy-scyllo-inositol kinase activity but to lack 1D-1-guanidino-3-amino-1,3-dideoxy-scyllo-inositol kinase activity, showing for the first time that these two reactions in streptomycin producers must be catalyzed by different enzymes. S. glebosus extracts therefore possess the same five enzymes required for synthesis of guanidinodeoxy-scyllo-inositol from myo-inositol that are found in streptomycin producers but lack the next three of the four enzymes found in streptomycin producers that are required to synthesize the second guanidino group of streptidine-P. In place of a second guanidino group, S. glebosus extracts were found to catalyze a Mg2(+)-dependent carbamoylation of guanidinodeoxy-scyllo-inositol to form bluensidine, followed by a phosphorylation to form bluensidine-P. The novel carbamoyl-P:guanidinodeoxy-scyllo-inositol O-carbamoyltransferase and ATP:bluensidine phosphotransferase activities were not detected in streptomycin producers or in S. glebosus during its early rapid growth phase. Free bluensidine appears to be a normal intermediate in bluensomycin biosynthesis, in contrast to the case of streptomycin biosynthesis; in the latter, although exogenous streptidine can enter the pathway via streptidine-P, free streptidine is not an intermediate in the endogenous biosynthetic pathway. Comparison of the streptomycin and bluensomycin biosynthetic pathways provides a unique opportunity to evaluate those proposed mechanisms for the evolutionary acquisition of new biosynthetic capabilities that involve gene duplication and subsequent mutational changes in one member of the pair. In this model, there are at least five pairs of enzymes catalyzing analogous reactions that can be analyzed for homology at both the protein and DNA levels, including two putative pairs of inositol kinases detected in this study.


Revision of the Old World Sobarocephala (Diptera: Clusiidae).
The Old World Sobarocephala Czerny, 1903 are revised, with 16 of the 29 known species described here as new: S. anonymos spec. nov., S. apoxys spec. nov., S. cycla spec. nov., S. doryphoros spec. nov., S. insolata spec. nov., S. kapnikos spec. nov., S. laticrinis spec. nov., S. magna spec. nov., S. myllolabis spec. nov., S. nebulosa spec. nov., S. nimbipennis spec. nov., S. orientalis spec. nov., S. paksana spec. nov., S. recava spec. nov., S. secaperas spec. nov., and S. triangula spec. nov. Species are mostly Oriental and Afrotropical in distribution, but species also occur in Japan, Nepal and northern Australia. Species mostly belong to the exclusively Old World S. plumicornis species group, but there are also representatives from the predominantly New World S. flava and S. flaviseta groups. Sobarocephala is described for the first time from Australia, China, Laos, Sri Lanka, Madagascar and West Africa. A key and illustrations are provided.


Surrogate losses: Understandings of pregnancy loss and assisted reproduction among surrogate mothers.
I explore surrogate mothers' narrative construction of pregnancy loss on surrogacy support websites. Communicating via the Internet, women construct the public online world of surrogacy. Drawing on anthropological and sociological literature I investigate the connections between conceptualizations of loss and understandings of technological practices and the consequences of these understandings for assisted reproduction. Surrogate mothers define loss broadly, ranging from failure to conceive to miscarriage and stillbirth; loss means the failure to give a baby to the intended parents. Assisted reproductive technologies contribute to loss by raising expectations of success, by attempting to maximize results through the transfer of multiple fertilized ova, and by early monitoring and testing. However, surrogates collectively understand technology as a positive force and advocate for reproductive technology. Surrogates' resolve to "give the gift of life" makes them vulnerable to failure and loss, yet also informs repeated efforts to bear children for others with technological assistance.


Molecular Reorganization Energy as a Key Determinant of J-Band Formation in J-Aggregates of Polymethine Dyes.
This work demonstrates the feasibility of the theory of extended multiphonon electron transitions for the description of optical spectra of polymethine dyes and J-aggregates using quantum chemistry. The formation of a strong absorption band in dye monomers and a J-band in their aggregates is uniformly explained from the electron-nuclear resonance condition. The redistribution of optical band intensities among cyanine dyes with the solvent is also explained. The dependence of the possibility of J-band formation in aggregates on the dye structure is successfully predicted. The results presented provide an insight for rational molecular design and application of polymethine dyes.


White blood cell count and endothelin-1 vasoconstrictor tone in middle-aged and older adults.
Higher white blood cell (WBC) count is associated with impaired endothelium-dependent vasodilation. However, the influence of higher WBC count on endothelin (ET)-1 vasoconstrictor activity is currently unknown. We tested the hypothesis that adults with elevated WBC count demonstrate enhanced ET-1 system activity. Thirty-four healthy adults were studied: 17 with WBC count < 5.0 × 109 cells/L (lower WBC; 9M/8F; age: 53 ± 2 yr) and 17 with WBC count > 5.0 × 109 cells/L (higher WBC; 10M/7F; 54 ± 3 yr). Forearm blood flow (FBF) responses to intra-brachial infusion of ET-1 (5 pmol/min for 20 min) and selective ETA receptor blockade (BQ-123; 100 nmol/min for 60 min) were measured by venous occlusion plethysmography. The vasoconstrictor response to ET-1 was significantly blunted (∼60%) in the higher WBC group versus the lower WBC group. The FBF responses to selective ETA receptor blockade were also significantly different (P < 0.05) between the groups. In the lower WBC group, resting FBF increased marginally (∼5%) to BQ-123, whereas the increase in FBF to BQ-123 was significantly greater (∼15%) in higher WBC group. Furthermore, there was a significant relation between WBC count and FBF response to ET-1 (r = -0.43) and BQ-123 (r = 0.41). Relative elevations in WBC count in middle-aged and older adults, independent of adiposity and other cardiometabolic risk factors, are associated with enhanced ET-1-mediated vasoconstrictor tone. Elevated ET-1 system activity may be a mechanism linking higher WBC count with increased cardiovascular risk.


A new cell-based innate immune receptor assay for the examination of receptor activity, ligand specificity, signalling pathways and the detection of pyrogens.
The pattern recognition receptors (PRRs) of the innate immune system are the first defence line of the immune system. Toll-like receptors (TLRs) are the most well known and the best examined of the PR receptors. In the last years TLRs had been studied in different ways resulting in a lot of new insights in the function and signalling pathways of these receptors. However, it was not possible to investigate individual combinations of the TLRs and their specific ligands, because of the complex network in immune signalling resulting in interference with each other. This work shows a new cell-based assay, established for the analysis of single PRRs or heterodimers. For this purpose NIH3T3 (mouse fibroblasts) were stably transfected with the NF-kappaB-inducible reporter gene secreted alkaline phosphatase (SEAP) together with the corresponding combinations of human TLRs and their co-receptors (e.g. TLR1/2, TLR2/6 and TLR4/CD14). The specificity of the respective cell lines was shown by induction with variations of specific and unspecific ligands (immune-stimulating components of microorganisms or synthetic ligands). Analysis via the NF-kappaB-dependent reporter gene SEAP allows a direct way to detect the human TLR-activity. Our results showed that this assay is highly sensitive and specific for the respective ligands. For the synthetic ligands Pam(2)CysSK(4) the assay demonstrates a detection limit of 1 pg/ml for TLR2/6. In summary, this test system allows the investigation of individual human PRR-receptors in a highly specific way, without interference with other immune components opening new avenues for novel insights in the innate immune system and its applications.


Morphological and functional study of dwarf neurons in the rat striatum.
Combination of morphological and electrophysiological techniques provided data, suggesting existence in the young rat striatum of a peculiar class of neurons, the neurogliaform or dwarf neurons. Striatal neurons (n = 92), intracellularly recorded from rat brain slices, were filled (one in each slice) with the intracellular marker biocytin, to compare physiological and morphological properties in the same cell. Moreover, some neurons (n = 7) were filled with biocytin plus the fluorescent calcium indicator fura-2, identifying cells during electrophysiological recording. Electrophysiological recording showed that striatal neurons had different firing patterns, suggestive in most cases (n = 80) of spiny neuron class and in others (n = 12) of interneuron class. Fura-2 injection clearly identified the body of six medium-sized cells and of one distinctive tiny cell. This small cell, however, showed a resting membrane potential and spontaneous and evoked firing pattern characteristic of striatal interneurons. Moreover, the fura-2 injected in such small neuron also completely filled the cell body of a near large neuron; the fura-2 fluorescence changed synchronously in the two paired neurons after electrical stimulation of the impaled small one. Accordingly, the biocytin staining identified the morphology of the small recorded neuron as a neurogliaform-like cell apposed to a dendrite of an aspiny neuron, suggesting that the dye injected in one neuron had diffused to the other of a different type. Furthermore, such heterologous dye coupling unexpectedly involved seven pairs of cells detected with biocytin staining (7.6% of the recorded neurons), invariably represented by a medium or large neuron on one side, and on the other side by a small (5.44 +/- 0.15 x 9.14 +/- 0.7 microns, mean +/- SD; n = 7) neurogliaform cell, roundish in shape with few slender and short processes, usually apposed to a dendrite of the companion neurons (six out of seven). In the other cases, the biocytin staining revealed in each slice either the morphology of single spiny or aspiny neurons (80.4% of recorded neurons), or of two-three medium-sized spiny neurons detected near to each other, suggesting that dye coupling had occurred typically between similar neurons (11.9% of the recorded neurons). These data suggest that some neurogliaform cells in the striatum of young rat can be identified as dwarf interneurons, that may be dye-coupled with neurons of different classes.


The Effect of Soft Tissue Infections on Device Performance in Adult Cochlear Implant Recipients.
The aim of this study was to examine the effect of cochlear implant (CI) site infection and its subsequent management on CI mapping and CI performance. Risk factors for CI infections and pathogens causing infections were reviewed. Treatment options for CI infections were examined. Retrospective case review. Tertiary referral center. Adult patients with a significant CI soft tissue infection from the Northern Cochlear Implant Programme, New Zealand over a 10-year period (August 2004 until August 2014). Patients were treated with intravenous antibiotics, washout and debridement or ex-plantation and reimplantation of CI. CI mapping results and implant performance before and after management of CI infections were compared. There were nine CI infections. Most patients (7/9) were treated with washout and debridement. One patient required removal of the CI and one patient was deemed medically unfit for a general anaesthetic and was managed conservatively with antibiotics alone. Seven patients received long-term antibiotics. Four patients were able to maintain CI performance after salvage treatment of the CI infection. Three patients had poorer CI performance after salvage treatment. One patient had reimplantation and became a nonuser due to only partial reinsertion. The pathophysiology of CI infections is complex. Infections can occur many years after CI surgery. The most common bacteria identified were Staphylococcus aureus, Pseudomonas aeruginosa, and skin commensals. Biofilms are present around implants that are removed from patients and biofilms may play a role in CI infections, but the mechanism of infection is not clear.


Childhood Helicobacter pylori infection and growth impairment in developing countries: a vicious cycle?
We hypothesize that infection with the gastric pathogen Helicobacter pylori in children in developing countries is the initiator of a vicious cycle of events that result ultimately in malnutrition and growth impairment. Acute infection with H. pylori is accompanied by hypochlorhydria, which facilitates the acquisition of other enteropathogens because of removal of the gastric acid barrier, which then results in diarrheal disease and iron-deficiency anemia. This is likely to occur most frequently in developing regions where the prevalence of H. pylori infection is disproportionately high and multiple enteric coinfections are common. The consequent synergistic impact of diarrheal disease and micronutrient deficiency on growth and cognitive function in children has significant public health implications for socioeconomic development in these countries.


Systolic pressure amplification in pedal arteries in children.
Sphygmomanometric indirect blood pressure readings on the arm were compared to direct blood pressure readings from the radial and pedal arteries in pediatric patients. The direct systolic pressure in the pedal arteries was significantly (p less than 0.001) greater (25.1 +/- 12.3 mm Hg) than the indirect arm systolic pressure. The direct systolic pressure from the radial artery was identical to the indirect systolic arm pressure. Although there were no statistical differences between direct and indirect diastolic pressures, correlations for diastolic pressures were relatively poor. These data indicate that (1) there is a significant and unpredictable amplification of systolic pressure in the pedal arteries which may result in erroneous diagnosis of hypertension or jeopardize early detection of circulatory shock, (2) indirect blood pressure measurement with the recommended cuff width (125% of arm diameter or 40% of arm circumference) accurately reflects direct systolic pressure in the radial artery, and (3) indirect blood pressure measurement gives a relatively poor prediction of direct diastolic pressures.


The role of thoracoscopic lymph node staging in esophageal cancer.
Unlike mediastinoscopy in lung cancer, there exists no standard minimally invasive test to stage esophageal cancer. If it were possible to obtain exact preoperative staging in esophageal cancer, patients could be separated prospectively to receive adjuvant therapy appropriately. We studied the feasibility and efficacy of thoracoscopic lymph node staging (TSLN) and laparoscopic lymph node staging (LSLN) in esophageal cancer. TSLN was performed in 45 patients with biopsy proven carcinoma of the esophagus. LSLN was done in the last 19 patients. TSLN was aborted in 3 pts due to adhesions. Thoracic LN stage was N0 in 39 patients and N1 in 3; celiac LN were negative in 13 and positive in 6 patients. Esophageal resection was performed in 30 patients after TSLN; 17 of these underwent LSLN. TSLN staging showed N0 lymph node status in 28 patients and N1 in 2 patients. Two of the 28 N0 patients (7%) were found at resection to have paraesophageal lymph node involvement (N1) and were thus understaged by TSLN. Thus TSLN was accurate in detecting the presence of thoracic LN in 28/30 cases (93%). LSLN staging found negative celiac nodes in 12 patients and positive LN in 5 patients. After esophagectomy, final pathology of the 12 N0 patients was N0 in 11 and positive LN in one patient. Thus, LSLN was accurate in detecting lymph node metastases in 16/17 patients (94%).


INFLATE: a protocol for a randomised controlled trial comparing nasal balloon autoinflation to no nasal balloon autoinflation for otitis media with effusion in Aboriginal and Torres Strait Islander children.
Otitis media with effusion (OME) is common and occurs at disproportionately higher rates among Indigenous children. Left untreated, OME can negatively affect language, development, learning, and health and wellbeing throughout the life-course. Currently, OME care includes observation for 3 months followed by consideration of surgical ventilation tube insertion. The use of a non-invasive, low-cost nasal balloon autoinflation device has been found beneficial in other populations but has not been investigated among Aboriginal and Torres Strait Islander children. This multi-centre, open-label, randomised controlled trial will determine the effectiveness of nasal balloon autoinflation compared to no nasal balloon autoinflation, for the treatment of OME among Aboriginal and Torres Strait Islander children in Australia. Children aged 3-16 years with unilateral or bilateral OME are being recruited from Aboriginal Health Services and the community. The primary outcome is the proportion of children showing tympanometric improvement of OME at 1 month. Improvement is defined as a change from bilateral type B tympanograms to at least one type A or C1 tympanogram, or from unilateral type B tympanogram to type A or C1 tympanogram in the index ear, without deterioration (type A or C1 to type C2, C3, or B tympanogram) in the contralateral ear. A sample size of 340 children (170 in each group) at 1 month will detect an absolute difference of 15% between groups with 80% power at 5% significance. Anticipating a 15% loss to follow-up, 400 children will be randomised. The primary analysis will be by intention to treat. Secondary outcomes include tympanometric changes at 3 and 6 months, hearing at 3 months, ear health-related quality of life (OMQ-14), and cost-effectiveness. A process evaluation including perspectives of parents or carers, health care providers, and researchers on trial implementation will also be undertaken. INFLATE will answer the important clinical question of whether nasal balloon autoinflation is an effective and acceptable treatment for Aboriginal and Torres Strait Islander children with OME. INFLATE will help fill the evidence gap for safe, low-cost, accessible OME therapies. Australia New Zealand Clinical Trials Registry ACTRN12617001652369 . Registered on 22 December 2017. The Australia New Zealand Clinical Trials Registry is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set. Retrospective registration.


Hypercalcemia with extraosseous MDP uptake in a bone scan as initial presentation in a case of cutaneous T-cell lymphoma.
A middle-aged lady presented with headache, vomiting of sudden-onset with intermittent evening rise of temperature. She also had slurring of speech with no loss of consciousness or altered sensorium. The patient was under evaluation for hypercalcemia. A whole body bone scan was done to look for causes of hypercalcemia and the scan showed extraosseous 99m Tc MDP (Technetium Methylene Di Phosphonate) uptake. One of the causes of extraosseous MDP uptake is cutaneous T-cell lymphoma (CTCL). On close interrogation the patient gave a history of hypopigmented dermal patches for more than 2 years duration. The coexisting dermal patches raised suspicion of CTCL. Skin biopsy confirmed CTCL. The patient was referred to oncology and was planned for six cycles of chemotherapy.


Does cage quantum delocalisation influence the translation-rotational bound states of molecular hydrogen in clathrate hydrate?
In this study, we examine the effect of a flexible description of the clathrate hydrate framework on the translation-rotation (TR) eigenstates of guest molecules such as molecular hydrogen. Traditionally, the water cage structure is assumed to be rigid, thus ignoring the quantum nature of hydrogen nuclei in the water framework. However, it has been shown that protons in a water molecule possess a marked delocalised character in many situations, ranging from water clusters to proton transfer in the bulk. In the case of water clathrates, all previous TR bound-state calculations of guest molecules consider that the caging water molecules are fixed at their equilibrium geometry. Only recently, a static investigation of the role of proton configurations was performed by Bačić and co-workers by sampling a very large number of different static structures of water clathrates. Here, we investigate the importance of the rotational degrees of freedom of the water cage on the TR levels of the guest molecule using an efficient adiabatic decoupling scheme. Our approach combines rigid body diffusion Monte Carlo calculations for the description of the rotational degree of freedom of water molecules surrounding the guest molecular hydrogen to an efficient Smolyak sparse-grid technique for the calculation of the TR levels. This approach allows us to take into account the highly anharmonic nature of the rotational water motions in a high-dimensional system. The clathrate-induced splittings of the j = 1 rotational levels are much more sensitive to the quantum hydrogen delocalisation than the translational transitions. This result is in good agreement with the previous static study of Bačić and co-workers.


Bone regeneration with a collagen model polypeptides/α-tricalcium phosphate sponge in a canine tibia defect model.
We evaluated the effects of synthesized collagen model polypeptides consisting of a proline-hydroxyproline-glycine (poly(PHG)) sequence combined with porous alpha-tricalcium phosphate (α-TCP) particles on bone formation in a canine tibia defect model. The porous α-TCP particles were mixed with a poly(PHG) solution, and the obtained sponge was then cross-linked and characterized by x-ray diffraction and scanning electron microscopy. Tibia defects were analyzed in 12 healthy beagles using microcomputed tomography and histological evaluation. At 2 and 4 weeks, the volume density of new bone was higher in the poly(PHG)/α-TCP group than in poly(PHG) alone group (P < 0.05); however, there was no difference at 8 weeks (P > 0.05). Histological evaluation at 4 weeks after implantation revealed that the poly(PHG) had degraded, and newly formed bone was present on the surface of the α-TCP particles. At 8 weeks, continuous cortical bone formation with a Haversian structure covered the top of the bone defects in both groups. This study demonstrates that the composite created using porous α-TCP particles and poly(PHG) is sufficiently adaptable for treating bone defects.


Role of reduced intensity conditioning in allogeneic hematopoietic cell transplantation for patients with multiple myeloma.
High-dose chemotherapy followed by autologous hematopoietic cell transplantation continues to play an integral role in the treatment strategy in patients with newly diagnosed multiple myeloma. Incorporation of newer potent anti-myeloma agents has further improved outcomes. However, disease relapse or progression remains a challenge after autologous transplantation. Allogeneic hematopoietic cell transplantation remains the only potentially curative modality for some patients due in part to graft-versus-myeloma effect. High transplant-related mortality, in the range of 30% to 40%, previously seen with myeloablative conditioning regimens, including total body irradiation plus cyclophosphamide has been significantly reduced by introducing less ablative preparative regimens, so called reduced-intensity conditioning. Cumulative evidence suggests encouraging prospects for allogeneic transplantation through improved outcomes of myeloma patients (overall survival exceeding 70% at 2 years in some studies); however, which patient population would benefit most from this treatment remains to be defined. newer strategies to augment graft-versus-myeloma effect and minimize post transplant toxicities are in need of further improvement in patients with myeloma.


Improved bone status by the beta-blocker propranolol in an animal model of nutritional growth retardation.
The aim of the present research was to study if the beta-blocker propranolol, which is known to increase bone mass, could reverse the adverse skeletal effects of mild chronic food restriction in weanling rats. Male Wistar rats were divided into four groups: control, control+propranolol (CP), nutritional growth retardation (NGR) and nutritional growth retardation+propranolol (NGRP). Control and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80 % of the amount of food consumed by the control and CP rats, respectively. Results were expressed as mean values and sem. Food restriction induced detrimental effects on body and femur weight and length (P < 0.05) and bone structural and geometrical properties (P < 0.001), confirming results previously shown in our laboratory. However, the beta-blocker overcame the deleterious effect of nutritional stress on load-bearing capacity, yielding load, bone stiffness, cross-sectional cortical bone area and second moment of inertia of the cross-section in relation to the horizontal axis without affecting anthropometric, histomorphometric and bone morphometric parameters. The results suggest that propranolol administration to mildly chronically undernourished rats markedly attenuates the impaired bone status in this animal model of growth retardation.


Spatial variation and predictors of missing birth preparedness and complication readiness (BPCR) messages in Ethiopia.
The Birth Preparedness and Complication Readiness (BPCR) message is one of the prenatal care packages targeted at reducing maternal and neonatal mortality by avoiding unnecessary delays during labor and delivery. There is limited evidence in Ethiopia that has looked at the spatial variation of missing BPCR messages and potential predictors. Hence, this study aimed to identify spatial predictors missing BPCR messages at the national level. The study was based on analysis of 2016 Ethiopia Demographic Health Survey data, using a weighted sample of 4771 women. Arc-GIS version 10.7 and SaTScan version 9.6 statistical software were used for the spatial analysis. To explore spatial variation and locate spatial clusters of missing BPCR messages, the Global Moran's I statistic and Bernoulli-based spatial scan (SaTScan) analysis were carried out, respectively. Hotspot (Getis-OrdGi*) analysis was conducted to identify Hotspots and Cold spotsof missing BPCR messages. Finally, spatial regression were carried out via ordinary least squares and geographically weighted regression to identify predictors of hotspots for missing BPCR messages. The overall prevalence of missing BPCR messages in Ethiopia was found to be 44.0% (95%CI: 42.6, 45.4%), with significant spatial variation across regions (Moran's I = 0.218, p-value<0.001) and seven most likely significant SaTScan clusters. The vast majority of Somali, central Afar, and Gambella regions were identified as statistically significant hotspots. Living in the poorest wealth quintile, having only one ANC visit, lack of access to listening to the radio, facing difficulty in accessing money, not having a mobile phone, and being not covered by health insurance were identified as significant spatial predictors of missing BPCR messages. The level of missing BPCR messages during pregnancy was found to be high in Ethiopia, with significant local variation. As a result, policymakers at the national level and local planners should develop strategies and initiatives that enhance women's economic capacities, health-seeking behavior, and media exposure. Furthermore, the regional authorities should focus on strategies that promote universal health coverage through enrolling citizens in health insurance schemes.


Effectiveness of telenutrition in a women's weight loss program.
Objective. The objective of this study is to evaluate the effectiveness of telenutrition versus traditional nutritional consultations for female obese patients in need of nutritional treatment. Methods. A comparative clinical study was conducted among 233 obese or overweight women (including 20 who dropped out and 60 who failed) who consulted a nutrition clinic in Barranquilla (Colombia) for nutritional assessment and chose either telenutrition or a traditional consultation that included a weekly follow-up consultation over 16 weeks, food consumption patterns, Body Mass Index (BMI, kg/m(2)) registeration and waist and hip circumference registeration. Treatment responses and differences between telenutrition and the traditional consultations were made according to BMI, waist, hip and initial-waist/height ratio (iWaist), calculating for the relative risk. Results. In 68 (29.2%) women who chose traditional attention, 9 (37.5%) dropped out, 24 (40%) failed and 35 (23.5%) were successful, showing 1.4% (1.0 SD) BMI loss, 5.8% (3.4 SD) in waist circumference, 4.5% (2.8 SD) in hip circumference and 0.04% (0.02 SD) in iWaist/height ratio. In 165 (70.8%) women who chose telenutrition, 15 (62.5%) dropped out, 36 (60%) failed and 114 (76.5%) were successful, showing 1.1% (1.0 SD) BMI loss, 5.0% (3.2 SD) in waist circumference, 3.5% (3.1 SD) in hip circumference and 0.03% (0.02 SD) in iWaist/height ratio. A significance level of p < 0.05 is considered. Conclusion. Telenutrition has a failure or dropout risk factor of about half of the value of traditional consultation, and showed slight, statistically significant differences. This study concludes that telenutrition can support or sometimes replace traditional consultations when developing weight loss programs for obese women.


Alpha- and beta-adrenergic receptor blockers and the effects of noradrenaline on heat production and body temperature.
Noradrenaline (NA) administered systemically or into the lateral cerebral ventricle (ICV) in appropriate doses increased heat production and colonic temperature in 1-12 day-old guinea pigs. The effect of systemically applied NA could be blocked by systemically applied beta-adrenergic receptor blockers, while beta-blockers administered centrally or alpha-adrenergic blockers injected systemically or centrally had no effect on the action of systemically applied NA. Accordingly, the effect of systemically applied NA was mediated by peripheral beta-adrenergic receptors. The effect of centrally applied NA was blocked by alpha-adrenergic receptor antagonists applied into the lateral cerebral ventricle and attenuated by systemically applied phentolamine, but not by phenoxybenzamine or ergotamine. Beta-adrenergic receptor blocking agents applied either ICV or systemically had no effect on the action of centrally applied NA. It is concluded that ICV applied NA acts through central alpha-adrenergic receptors.


Visual Analytic Tools and Techniques in Population Health and Health Services Research: Protocol for a Scoping Review.
Visual analytics (VA) promotes the understanding of data using visual, interactive techniques and using analytic and visual engines. The analytic engine includes machine learning and other automated techniques, whereas common visual outputs include flow maps and spatiotemporal hotspots for studying service gaps and disease distribution. The principal objective of this scoping review is to examine the state of science on VA and the various tools, strategies, and frameworks used in population health and health services research (HSR). The purpose of this scoping review is to develop an overarching global view of established techniques, frameworks, and methods of VA in population health and HSR. The main objectives are to explore, map, and synthesize the literature related to VA in its application to the two main focus areas of health care. We will use established scoping review methods to meet the study objective. As the use of the term visual analytics is inconsistent, one of the major challenges was operationalizing the concepts for developing the search strategy, based on the three main concepts of population health, HSR, and VA. We included peer reviewed and grey literature sources from 2005 till March 2019 in the search. Independent teams of researchers will screen the titles, abstracts and full text articles, whereas an independent researcher will arbiter conflicts. Data will be abstracted and presented using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist and explanation by two independent researchers. As of late August 2019, the scoping review is in the full-text screening stage. Data synthesis will follow and the first results are expected to be submitted for publication in December 2019. In this protocol, the methods for undertaking this scoping review are detailed. We present how we operationalized the varied concepts of population health, health services, and VA. The main results of the scoping review will synthesize peer reviewed and grey literature sources on the main methods of VA in the interrelated fields of population health and health services research from January 2005 till March 2019. VA is being increasingly used and integrated with emerging technologies to support decision making using large data sets. This scoping review of the VA tools, strategies, and frameworks applied to population health and health services aims to increase awareness of this approach for uptake by decision makers working within and toward developing learning health systems globally. DERR1-10.2196/14019.


Cross-species bacterial artificial chromosome-fluorescence in situ hybridization painting of the tomato and potato chromosome 6 reveals undescribed chromosomal rearrangements.
Ongoing genomics projects of tomato (Solanum lycopersicum) and potato (S. tuberosum) are providing unique tools for comparative mapping studies in Solanaceae. At the chromosomal level, bacterial artificial chromosomes (BACs) can be positioned on pachytene complements by fluorescence in situ hybridization (FISH) on homeologous chromosomes of related species. Here we present results of such a cross-species multicolor cytogenetic mapping of tomato BACs on potato chromosomes 6 and vice versa. The experiments were performed under low hybridization stringency, while blocking with Cot-100 was essential in suppressing excessive hybridization of repeat signals in both within-species FISH and cross-species FISH of tomato BACs. In the short arm we detected a large paracentric inversion that covers the whole euchromatin part with breakpoints close to the telomeric heterochromatin and at the border of the short arm pericentromere. The long arm BACs revealed no deviation in the colinearity between tomato and potato. Further comparison between tomato cultivars Cherry VFNT and Heinz 1706 revealed colinearity of the tested tomato BACs, whereas one of the six potato clones (RH98-856-18) showed minor putative rearrangements within the inversion. Our results present cross-species multicolor BAC-FISH as a unique tool for comparative genetic studies across Solanum species.


Hippocampal-dependent learning requires a functional circadian system.
Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.


A Case of Chronic Infectious Arthritis of the Temporomandibular Joint Associated with Osteomyelitis without Malocclusion.
Infectious arthritis of the temporomandibular joint (TMJ) is rare, and previous reports have identified malocclusion resulting from condylar deformity and displacement of the condyle as one of the clinical characteristics of the disease. Here we report the case of a 33-year-old man with chronic infectious arthritis of the TMJ without malocclusion associated with osteomyelitis of the right mandible. Based on radiological findings of more prominent inflammation at the TMJ than in other regions and on the observed efficacy of antibiotic administration, we made a diagnosis of suppurative arthritis of the TMJ. Based on our empirical experience, including the present case, we speculate that refusal to cooperate with medical care may be a factor in the development of infectious arthritis of the TMJ.


Agro-morphological characterization of a population of introgression lines derived from crosses between IR 64 (Oryza sativa indica) and TOG 5681 (Oryza glaberrima) for drought tolerance.
The study evaluated effects of drought on some agro-morphological traits of 60 rice genotypes comprising 54 introgression lines with their parents, IR 64 (Oryza sativa) and TOG 5681 (Oryza glaberrima) and four NERICA-L varieties developed from the same parents for comparison. The genotypes were subjected either to full irrigation from sowing to maturity (control) or to 21-day drought applied by stopping irrigation from the 45th day after sowing (DAS) onward (drought) in the dry seasons of 2006 and 2007-2008. Plant height, spikelet fertility, grain yield and leaf area at harvesting were consistently reduced by drought in both seasons. Values of leaf temperature, leaf rolling, leaf tip drying, leaf blast, days from seeding to flowering and maturity were higher under drought. The results on SPAD and number of tillers were not consistent. Significant relationship (P<0.05) was observed between all traits evaluated and grain yield under drought. Introgression lines, SEN-L13-2, MPL-15-3, SEN-L10-1, SEN-L26-3 and SEN-L21-2 showed significantly higher yield than the highest yield NERICA-L variety (all of them had higher yield than the parents). Among them, SEN-L13-2 showed the lowest yield loss by drought and MPL-15-3 had high yield potential and considerably low yield loss by drought.


Crafting in context: Exploring when job crafting is dysfunctional for performance effectiveness.
Job crafting theory purports that the consequences of revising one's work role can be simultaneously beneficial and detrimental. Previous research, however, has almost exclusively emphasized the beneficial outcomes of job crafting. In the current study, we proposed dysfunctional consequences of crafting for performance-related outcomes in the form of a U-shaped relationship between job crafting and performance effectiveness (managerial ratings of job proficiency and peer ratings of citizenship behavior). We further predicted that elements of the task context (autonomy and ambiguity) and the social context (interdependence and social support) moderate these curvilinear relationships. Consistent with previous research, job crafting displayed positive and linear effects on work-related attitudes (job satisfaction and affective commitment). Consistent with our predictions, moderate levels of crafting were associated with dysfunctional performance-related outcomes and features of work context either exacerbated or dissipated these dysfunctional consequences of job crafting for individuals. (PsycINFO Database Record


Reduced ferritin levels in individuals with non-O blood group: results from the Danish Blood Donor Study.
Genomewide association studies have reported alleles in the ABO locus to be associated with ferritin levels. These studies warrant the investigation of a possible association between the ABO blood group and ferritin levels. We aimed to explore if ABO blood group is associated with iron stores expressed as ferritin levels. Ferritin levels were measured at least once for 30,595 Danish Blood Donor Study participants. Linear regression analyses were performed with the ABO blood group as explanatory variable and adjusted for age, number of donations 3 years before the ferritin measurement, and time since latest donation. In addition, a subanalysis was performed on 15,280 individuals in which further adjustments for body mass index, smoking status, and C-reactive protein levels were possible. Furthermore, logistic regression analyses were performed to determine if ABO blood group was associated with a ferritin level of less than 15 ng/mL. Non-O blood group donors had lower ferritin levels than blood group O donors, regardless of sex. Accordingly, risk of ferritin level of less than 15 ng/mL was increased for individuals with non-O blood group compared with O blood group. In subanalyses similar associations were observed, albeit in women the association between blood group and risk of a ferritin level below 15 ng/mL was no longer significant. ABO blood group was not associated with red blood cell indices such as mean cell volume and mean cell hemoglobin content. Donors with non-O blood group have lower ferritin levels than donors with other blood groups.


Grb2-associated binding protein-1 as a biomarker in bone and soft tissue sarcomas.
The Grb2-associated binding proteins are a family of platform proteins involved in signalling transduction pathways. A major family member, Gab1, modulates the effect of growth factor receptors and intracellular signalling pathways, including the phosphatidylinositol 3-kinase and AKT/mTOR signalling pathways. We have studied the immunohistochemical staining of Gab1 in four separate tissue microarray slides containing Ewing sarcoma, rhabdomyosarcoma, osteosarcoma and synovial sarcoma. The expression of Gab1 was correlated with age, gender, tumour location and clinical stage. Positive staining was identified in 18/32 (56.25%) of Ewing sarcoma, 46/96 (48%) of rhabdomyosarcoma, 18/50 (36%) of synovial sarcoma, and 10/40 (25%) osteosarcoma. Of the 46 positive rhabdomyosarcoma cases, the staining was more prevalent in conventional embryonal (15/27 cases) and pleomorphic (21/30) subtypes than spindle cell (2/15) and alveolar types (8/24). For rhabdomyosarcoma and synovial sarcoma, positive Gab1 staining was significantly more prevalent in tumours of high clinical stage disease (stages III and IV) than low stages (I and II), (p=0.0042 and p=0.0024, respectively). Similarly, Gab1 staining in Ewing sarcoma revealed a significant association with advanced clinical stages (p=0.0189). In conclusion, Gab1 expression in Ewing sarcoma, rhabdomyosarcoma and synovial sarcoma may have prognostic significance and should be further exploited for potential benefit from targeted therapy. These findings are to be confirmed by larger studies with better represented patient populations.


Effects of export concentration on CO2 emissions in developed countries: an empirical analysis.
This paper provides the evidence on the short- and the long-run effects of the export product concentration on the level of CO2 emissions in 19 developed (high-income) economies, spanning the period 1962-2010. To this end, the paper makes use of the nonlinear panel unit root and cointegration tests with multiple endogenous structural breaks. It also considers the mean group estimations, the autoregressive distributed lag model, and the panel quantile regression estimations. The findings illustrate that the environmental Kuznets curve (EKC) hypothesis is valid in the panel dataset of 19 developed economies. In addition, it documents that a higher level of the product concentration of exports leads to lower CO2 emissions. The results from the panel quantile regressions also indicate that the effect of the export product concentration upon the per capita CO2 emissions is relatively high at the higher quantiles.


Characterization of a specific somatomedin-c receptor on isolated bovine growth plate chondrocytes.
The interaction of somatomedin (Sm) with growth plate chondrocytes (GPCs) is believed to be the primary stimulus of skeletal growth. Using techniques designed to disrupt as little as possible the phenotypic characteristics of GPCs, we have been able to obtain 3-4 x 10(8) viable cells from the major physes of one newborn calf. The availability of these cells plus essentially pure Sm-C/insulin-like growth factor I, the most GH-dependent Sm, has now made possible detailed studies of the interaction of this radiolabeled peptide with the GPC receptor and of the subsequent processing of this hormone by these cells. The enzymatic methods required to free GPCs from their matrix led to loss of receptors, followed by rapid receptor regeneration by de novo synthesis in suspension cultures. Binding of [125I]iodo-Sm-C to GPCs was time dependent and saturable, with optima at 15 C and pH 7.8. At 37 C, binding peaked at 90 min and declined thereafter. Multiplication-stimulating activity, insulin, and nerve growth factor were less potent than unlabeled Sm-C in competition with [125I]iodo-Sm-C for its receptor. Human GH, epidermal growth factor, and fibroblast growth factor failed to show competition even at 10(-6) M. Analysis of the fate of [125I]iodo-Sm-C bound to GPCs at 37 C provided evidence that this hormone is internalized and extruded from the cell in a partially degraded form. Scatchard analysis of [125I]iodo-Sm-C binding to GPCs and to chondrocytes isolated from articular cartilage revealed similar Ka values, but reproducibly 2-6 times more receptors on growth plate than on articular chondrocytes.


Schistura megalodon species nova, a new river loach from the Irra-waddy basin in Dehong, Yunnan, China (Teleostei: Cypriniformes: Nemacheilidae).
A new species of river loach, Schistura megalodon sp. nov., is described from the Irrawaddy basin in Yingjiang County, Dehong Autonomous Prefecture, Yunnan Province, China. The following combination of diagnostic characters serve to distinguish it from all other congeners in the given zoogeographical region: a large processus dentiformes in the upper jaw, a short pre-anus length of 65.4%-66.3% of SL, long paired fins (pectoral: 20.8%-24.2% of SL; pelvic: 17.9%-20.6% of SL), a wide body of 9.7%-11.3% of SL at anal fin origin, an incomplete lateral line, the absence of an orbital lobe, and a oad and distinct basicaudal bar with forward extensions.


Testing the effectiveness of techniques for reducing heat strain in Royal Navy nuclear, biological and chemical cleansing stations' teams.
Nine personnel simulating the work of an NBC cleansing station (CS) in conditions expected in Middle Eastern waters had a limited work duration due to incapacitating heat strain. When the subjects were allowed five minutes rest periods after every 10 minutes of work, the endurance of seven of the subjects was limited to between 75-105 minutes due to heat strain and heat illness. By the point of withdrawal mean (SD) rectal temperature (Tre) had risen by 1.8 degrees C (0.4 degree C). The other two subjects were withdrawn earlier because they reached cardiac safety limits. When the hands were immersed (HI) in 10 degrees C water during the five minute rest periods heat strain was significantly lower (P < 0.01) and work endurance times were increased. One subject was withdrawn early on reaching cardiac safety limits, two on reaching Tre limits (39 degrees C) at 105 minutes, and six subjects completed the 180 minute exposure with a final Tre of 38.4 degrees C (0.3 degree C). Using 'iced' (0 degree C) rather than 10 degrees C water for HI further reduced heat strain (P < 0.01) and increased endurance times. Three subjects were withdrawn early on reaching cardiac safety limits, the remaining six completing the 180 minute exposure, with a final Tre of 38.3 degrees C (0.5 degree C). Using an ice-vest (IV) in conjunction with HI further reduced heat strain (P < 0.01) and increased endurance times. Two subjects were withdrawn early on reaching cardiac safety limits, the remaining seven completing the 180 minute exposure, with a final Tre of 38.2 degrees C (0.8 degree C) when 10 degrees C HI water was used, and Tre 38.0 degrees C (0.4 degree C) when 0 degree C HI water was used. There were no reports of finger numbness or loss of dexterity due to HI, and all personnel were able to remove their own individual Protective Equipment (IPE) without difficulty. It is expected that using HI will not reduce the ability to decontaminate or undress others. The HI technique and IV equipment should be introduced into the Fleet. 'Iced' water should be used in preference to 10 degrees C, although any water colder than 25 degrees C will provide some benefit. The IVs increased torso girth and personnel should try them on (with frozen ice packs inserted) prior to their use and ensure that their protective clothing still fits, or obtain a larger size.


Peritonectomy and hyperthermic antiblastic perfusion in the treatment of peritoneal carcinomatosis.
Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.


[Dynamics of nitrogen, phosphorus, and potassium content in shoots of plants in urban plantations].
The characteristics of dynamics of total nitrogen, potassium, and phosphorus content in the shoots of plants growing in plantations of different environmental categories in a large industrial center were studied. In the urban environment, an increased nitrogen content in plant shoots, the disturbance of the balance of the basic mineral elements and change in their distribution pattern in structural parts of plant shoots, and the disturbance of autumnal physiological efflux of elements from leaves to dormant shoots were detected.


Ramipril in High-Risk Patients With COVID-19.
Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors. This study analyzed whether RAAS inhibitors modify the risk for COVID-19. The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril's impact on COVID-19 risk in this vulnerable population. As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039). In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185).


[Surgically treated megaesophagus: epidemiological profile of patients operated in the Clinical Hospital of the State University of Campinas between 1989 and 2005].
Megaesophagus is one of the manifestations of Chagas disease and surgical treatment is the approach that presents the best results. In this retrospective study, the epidemiological profile of patients operated in the Clinical Hospital of University of Campinas between 1989 and 2005 was evaluated with regard to: place of birth, place of residence, probable place of infection, age, degree of megaesophagus, etiology, duration and evolution of dysphagia, other diseases in association and the type of surgery chosen. The method used was to analyze the 390 medical files of these patients, at the hospitals medical archive service. The results made it possible to establish the endemic regions, place of birth and place of residence of the patients with Chagas disease attended at our clinic, and to characterize the group. After detailed analysis, it was found that the mean age was 47 years and the mean duration of dysphagia was 9.47 years. It was observed that: a) in 84.4% of the patients, dysphagia took hold progressively; b) 306 (78.5%) patients presented Chagas disease etiology; c) grade 2 was prevalent in 48%; d) 89.8% of the patients underwent cardiomyotomy; and e) there were frequent associations with gastritis, esophagitis, megacolon, arterial hypertension and cardiopathy.


Pain expression in children with an intellectual disability.
Children with an intellectual disability (ID) are sometimes unable to verbalize and describe their painful experience; therefore family members and health carers can assess the intensity of the pain only from the behaviour exhibited by the children. The purpose of this descriptive and exploratory study was to examine the behavioural pain expression in 30 children with ID aged from 5 to 18 years in a surgical context. Children were matched with 30 typically developing children of the same chronological age and 30 typically developing children of the same developmental age. The results showed the influence of the level of expressive communication on the pain expression. Children who were able to verbalize their pain exhibited a normative pain expression with behavioural traits similar to those of typically developing children of the same developmental age. Children who were unable to verbalize their pain produced particular pain expressions with behavioural traits that were atypical and without a communicative goal. Pain expression modalities are extremely different between children able to verbalize their pain and those unable to do so. This study confirmed the necessity to take into account the particularities of each child with ID in order to individualize the pain management and avoid misdiagnosis and the under treating of pain in non verbal children.


4-Aminobutyrate:2-oxoglutarate aminotransferase from Candida. Purification and properties.
An enzyme which catalyzes the transamination of 4-aminobutyrate with 2-oxoglutarate was purified 588-fold to homogeneity from Candida guilliermondii var. membranaefaciens, grown with 4-aminobutyrate as sole source of nitrogen. An apparent relative molecular mass of 107,000 was estimated by gel filtration. The enzyme was found to be a dimer made up of two subunits identical in molecular mass (Mr 55,000). The enzyme has a maximum activity in the pH range 7.8-8.0 and a temperature optimum of 45 degrees C. 2-Oxoglutarate protects the enzyme from heat inactivation better than pyridoxal 5'-phosphate. The absorption spectrum of the enzyme exhibits two maxima at 412 nm and 330 nm. The purified enzyme catalyzes the transamination of omega-amino acids; 4-aminobutyrate is the best amino donor and low activity is observed with beta-alanine. The Michaelis constants are 1.5 mM for 2-oxoglutarate and 2.3 mM for 4-aminobutyrate. Several amino acids, such as alpha,beta-alanine and 2-aminobutyrate, are inhibitors (Ki = 38.7 mM, Ki = 35.5 mM and Ki = 33.2 mM respectively). Propionic and butyric acids are also inhibitors (Ki = 3 mM and Ki = 2 mM).


Differentiating lymphovascular invasion from retraction artifact on histological specimen of breast carcinoma and their implications on prognosis.
On a pathological specimen of breast cancer cells, retraction artifact during histological processing mimics true lymphovascular invasion (LVI). The accurate determination of the presence or absence of LVI is a factor in determining risk of having a positive sentinel node, or having additional positive axillary nodes after a positive sentinel node biopsy in women with early-stage breast cancer. The determination of nodal risk influences the decision of the treating physicians as to whether a sentinel node biopsy or completion axillary dissection is necessary. On slide preparation, ideal factors favoring true LVI include: a definite endothelial lining, with endothelial nuclei that seem to protrude into the lymphatic space; invasion in one lymphatic vessel (LV) lumen with nearby cancer glands that have minimal or no retraction; a tumor embolus in a LV clear lumen with outside nearby tumor bulk; a tumor embolus that is different in shape than its surrounding clear LV space; and a positive stain for fibrin, CD31, or CD34 on tumor embolus periphery.


Post-antibiotic effect of orbifloxacin against Escherichia coli and Pseudomonas aeruginosa isolates from dogs.
Orbifloxacin is a fluoroquinolone drug used widely in companion animal medicine. In this study, we firstly determined post-antibiotic effects (PAEs) and post-antibiotic sub-minimum inhibitory concentrations (MIC) effects (PA-SMEs) of orbifloxacin for two strains each of Escherichia coli and Pseudomonas aeruginosa from dogs, and these parameters were compared with those of enrofloxacin. At twice the MIC, the PAEs of orbifloxacin ranged from -0.28-0.93 h (mean, 0.29 h) for E. coli and -0.18-1.18 h (mean, 0.37 h) for P. aeruginosa. These parameters were not significantly different for E. coli and shorter for P. aeruginosa, compared to enrofloxacin (P < 0.05). Continued exposure to 0.1, 0.2, and 0.3 the MIC of orbifloxacin resulted in average PA-SMEs of 0.55, 1.11, and 2.03 h, respectively, for E. coli, and 1.04, 1.40, and 2.47 h, respectively, for P. aeruginosa. These PA-SMEs, which had no significant differences with those of enrofloxacin, were significantly longer than the corresponding PAEs (P < 0.05). These results suggest that the PA-SME of orbifloxacin for E. coli and P. aeruginosa can be meaningfully prolonged by increase of sub-MICs.


Composition and structure of the venus atmosphere: results from pioneer venus.
Results from the Pioneer Venus sounder probe neutral mass spectrometer indicate that there is no difference in the isotopic ratios of carbon and oxygen between Venus and Earth to within +/- 5 percent. The mixing ratio of nitrogen is 3.5(+3)(-2) percent with an isotopic ratio within 20 percent of that of Earth. The ratio of argon-36 to argon-40 is 85 percent, and the ratio of argon-38 to argon-36 is 20 percent. The mixing ratios of argon-36 and argon-40 are approximately 40 and 50 parts per million, respectively, with an error of about a factor of 2 (mainly toward a lesser amount) resulting from uncertainty in the response of the ion pump to rare gases. Hydrogen chloride cannot account for more than a few percent of the 36 mass peak, and therefore the large excess of primordial argon is a reasonable conclusion. The ratio of neon-20 to argon-36 of 0.5 +/- 0.3 is definitely terrestrial in character rather than solar. These results indicate that there is a large excess of all primordial noble gases on Venus relative to Earth. There appears to be a considerably higher abundance of sulfur compounds below 20 kilometers than in or above the main cloud layer. The 32 and 60 mass peaks show a sharp increase below 22 kilometers, indicating the possible production of sulfur and carbon oxysulfide (COS) at the expense of sulfur dioxide.


Phenotypic characterization of two novel cell line models of castration-resistant prostate cancer.
Resistance to androgen deprivation therapies is a major driver of mortality in advanced prostate cancer. Therefore, there is a need to develop new preclinical models that allow the investigation of resistance mechanisms and the assessment of drugs for the treatment of castration-resistant prostate cancer. We generated two novel cell line models (LAPC4-CR and VCaP-CR) which were derived by passaging LAPC4 and VCaP cells in vivo and in vitro under castrate conditions. We performed detailed transcriptomic (RNA-seq) and proteomic analyses (SWATH-MS) to delineate expression differences between castration-sensitive and castration-resistant cell lines. Furthermore, we characterized the in vivo and in vitro growth characteristics of these novel cell line models. The two cell line derivatives LAPC4-CR and VCaP-CR showed castration-resistant growth in vitro and in vivo which was only minimally inhibited by AR antagonists, enzalutamide, and bicalutamide. High-dose androgen treatment resulted in significant growth arrest of VCaP-CR but not in LAPC4-CR cells. Both cell lines maintained AR expression, but exhibited distinct expression changes on the mRNA and protein level. Integrated analyses including data from LNCaP and the previously described castration-resistant LNCaP-abl cells revealed an expression signature of castration resistance. The two novel cell line models LAPC4-CR and VCaP-CR and their comprehensive characterization on the RNA and protein level represent important resources to study the molecular mechanisms of castration resistance.


"Are They Listening, and Do They Find It Useful?"-Evaluation of Mid-Rotation Formative Subjective and Objective Feedback to Radiology Trainees.
Residents commonly receive only end-of-rotation evaluations and thus are often unaware of their progress during a rotation. In 2021, our neuroradiology section instituted mid-rotation feedback in which rotating residents received formative subjective and objective feedback. The purpose of this study was to describe our feedback method and to evaluate if residents found it helpful. Radiology residents rotate 3-4 times on the neuroradiology service for 1-month blocks. At the midpoint of the rotation (2 weeks), 7-10 neuroradiology attendings discussed the rotating residents' subjective performance. One attending was tasked with facilitating this discussion and taking notes. Objective metrics were obtained from our dictation software. Compiled feedback was relayed to residents via email. A 16-question anonymous survey was sent to 39 radiology residents (R1-R4) to evaluate the perceived value of mid-rotation feedback. Odds ratios and 95% confidence intervals were computed using logistic regression. Sixty-nine percent (27/39) of residents responded to the survey; 92.6% (25/27) of residents reported receiving mid-rotation feedback in ≥50% of neuroradiology rotations; 92.3% (24/26) of residents found the subjective feedback helpful; 88.4% (23/26) of residents reported modifying their performance as suggested (100% R1-R2 vs 70% R3-R4; OR: 15.4 CI:1.26, >30.0);59.1% (13/22) of residents found the objective metrics helpful (75% R1-R2 vs 40% R3-R4; OR: 3.92 CI:0.74, 24.39) and 68.2% (15/22) stated they modified their performance based on these metrics (83.3% R1-R2 vs 50.0% R3-R4; OR:4.2 CI:0.73, 30.55); and 84.6% (22/26) of residents stated that mid-rotation subjective feedback and 45.5% (10/22) stated that mid-rotation objective feedback should be implemented in other sections. Majority of residents found mid-rotation feedback to be helpful in informing them about their progress and areas for improvement in the neuroradiology rotation, more so for subjective feedback than objective feedback. The majority of residents stated all rotations should provide mid-rotation subjective feedback.


Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer.
In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.


Cancer and COVID-19: economic impact on households in Southeast Asia.
The ongoing COVID-19 pandemic may worsen the existing financial vulnerabilities of cancer survivors who may be experiencing a double financial hit, both from cancer-induced financial toxicity as well as economic strains arising from loss of income and prolonged unemployment following the pandemic. The impact of the pandemic is likely to be more pronounced on cancer survivors living in resource-limited settings, such as in Southeast Asia. As health care systems in the region try to streamline resources and accommodate the influx of patients from COVID-19, many in the cancer community have experienced severe disruptions in their care. The delays and disruption of timely access to cancer care could lead to patients presenting with worsened conditions and at more advanced cancer stages in which treatment options tended to be costlier. Similar to countries around the world, the various forms of movement restrictions that were enforced have aggravated the rates of unemployment, loss of wages and the limited access to support from family or friends around Southeast Asia. The economic impact of COVID-19 hits even harder on the large proportion of the population in the region that works in the informal sector, who are often one paycheque or one episode of illness away from financial catastrophe. More worryingly, the lack of a robust social security system in many Southeast Asian countries, especially in terms of income protection, could ultimately force many cancer survivors to choose between paying for their treatments, or to forego treatments, and feed their families. Early identification of cancer patients experiencing financial toxicity following the pandemic will enable timely and appropriate interventions to be undertaken by various stakeholders, potentially averting a cascade of other economic fallouts that may last for years after cancer treatment.


Role of complement in rats injected with liposome-encapsulated hemoglobin.
Previous studies have documented that liposome-encapsulated hemoglobin (LEH) can cause a rapid and transient thrombocytopenia following intravenous injection into small animals. The present study evaluated the role of complement during the LEH-induced thrombocytopenia in rats. We have compared changes in platelet levels in the blood, platelet organ distribution, and total hemolytic complement levels following intravenous administration of LEH in control and complement-depleted rats. Changes in platelet organ distribution at various times after LEH administration were monitored by labeling autologous platelets with indium-111 (111In)-oxine and imaging the 111In-platelets with a gamma camera after reinjection. Platelet counts were determined by light-scattering methods and by following 111In radioactivity at various times after LEH administration. Platelet levels did not significantly change for the complement-depleted rats during the 60 min following an injection of LEH, whereas thrombocytopenia (40% decrease) was noted within 4 min post-LEH-injection for control rats with a gradual return to baseline circulating platelet levels within 60 min. This drop in circulating platelets was correlated with a rapid redistribution of 111In-platelets from the circulation to the lungs and liver, whereas complement-depleted rats showed no transient movement of the 111In-platelets from the circulation. Baseline complement levels of 21.6 +/- 2.2 CH50/ml for control rats and 0.2 +/- 0.1 CH50/ml for complement-depleted rats did not significantly change during the 60 min following LEH administration. This study suggests that complement must be present during LEH-induced transient thrombocytopenia, as complement-depleted rats underwent no thrombocytopenia, and that the transient LEH-induced thrombocytopenia may be associated with complement activation.


The assessment of scapular radiographs: analysis of anteroposterior radiographs of the shoulder and the effect of rotational offset on the glenopolar angle.
The glenopolar angle assesses the rotational alignment of the glenoid and may provide prognostic information and aid the management of scapula fractures. We have analysed the effect of the anteroposterior (AP) shoulder radiograph rotational offset on the glenopolar angle in a laboratory setting and used this to assess the accuracy of shoulder imaging employed in routine clinical practice. Fluoroscopic imaging was performed on 25 non-paired scapulae tagged with 2 mm steel spheres to determine the orientation of true AP views. The glenopolar angle was measured on all the bony specimens rotated at 10° increments. The mean glenopolar angle measured on the bone specimens in rotations between 0° and 20° and thereafter was found to be significantly different (p < 0.001). We also obtained the AP radiographs of the uninjured shoulder of 30 patients treated for fractures at our centre and found that none fitted the criteria of a true AP shoulder radiograph. The mean angular offset from the true AP view was 38° (10° to 65°) for this cohort. Radiological AP shoulder views may not fully project the normal anatomy of the scapular body and the measured glenopolar angle. The absence of a true AP view may compromise the clinical management of a scapular fracture.


Real-world effectiveness of umeclidinium/vilanterol versus fluticasone propionate/salmeterol as initial maintenance therapy for chronic obstructive pulmonary disease (COPD): a retrospective cohort study.
Retrospective claims data in patients with chronic obstructive pulmonary disease (COPD) initiating maintenance therapy with inhaled fixed-dose combinations of long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) versus inhaled corticosteroid (ICS)/LABA have not been reported. Retrospective observational study in a COPD-diagnosed population of commercial and Medicare Advantage with Part D (MAPD) enrollees aged ≥40 years from a US health insurer database. Patients initiated umeclidinium/vilanterol (UMEC/VI [62.5/25 µg]) or fluticasone propionate/salmeterol (FP/SAL [250/50 µg]) between April 1, 2014 and August 31, 2016 (index date) and had 12 months continuous enrollment pre- and post-index. Exclusion criteria included an asthma diagnosis in the pre-index period/index date; ICS-, LABA-, or LAMA-containing therapy during the pre-index period; or pharmacy fills for both UMEC/VI and FP/SAL, multiple-inhaler triple therapy, a non-index therapy, or COPD exacerbation on the index date. Adherence (proportion of days covered [PDC] ≥80%) was modeled using weighted logistic regression following inverse probability of treatment weighting (IPTW). Weighted Kaplan-Meier and Cox proportional hazards regression following IPTW were performed for incidence of COPD exacerbation and escalation to multiple-inhaler triple therapy. The study population included 5306 patients (1386 initiating UMEC/VI and 3920 initiating FP/SAL). Adjusted odds of adherence were 2.00 times greater among UMEC/VI than FP/SAL initiators (95% confidence interval [CI]: 1.62─2.46; P<0.001). The adjusted hazard ratio (HR) for first exacerbation was 0.87 (95% CI: 0.74-1.01; P=0.067) among UMEC/VI versus FP/SAL initiators. UMEC/VI initiators had 35% lower adjusted risk of escalation to multiple-inhaler triple therapy (HR 0.65; 95% CI: 0.47-0.89; P=0.008) versus FP/SAL. On-treatment, UMEC/VI initiators had an adjusted 30% reduced risk of a first moderate/severe COPD exacerbation (HR 0.70; 95% CI: 0.54-0.90; P=0.006). Patients with COPD initiating UMEC/VI had higher adherence and longer time before escalation to multiple-inhaler triple therapy than FP/SAL initiators.


Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir.
The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (β-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to β-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 ± 107, 1040.44 ± 132, and 1563.72 ± 171 μmol/g of free thiol groups attached to the β-CD-SH851, β-CD-SH1040, and β-CD-SH1563, respectively. β-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of β-CD-SH1563 was improved 7.6-fold in comparison to unmodified β-CD. β-CD-SH851, β-CD-SH1040, and β-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with β-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, β-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv.


Ultrasound and CT imaging assessment of renal angiomyolipoma.
The authors report a case of a 41-year-old woman who was admitted to the emergency department of our hospital because of acute right flank pain. Laboratory investigations and cultures were negative. A transabdominal ultrasonography revealed a large mass of the upper pole of the right kidney as an incidental finding.


Turf toe repair: a technical note.
Turf toe injury typically describes an injury to the metatarsosesamoid complex of the hallux generally caused by a hyperextension force to the great toe. This injury may be accompanied by pain, deformity, and decreased athletic performance. Operative treatment to repair the damaged tissue can be difficult, and we present a technique description that may help simplify the surgical reconstruction.


Characterization and frequency of a newly identified HIV-1 BF1 intersubtype circulating recombinant form in São Paulo, Brazil.
HIV circulating recombinant forms (CRFs) play an important role in the global and regional HIV epidemics, particularly in regions where multiple subtypes are circulating. To date, several (>40) CRFs are recognized worldwide with five currently circulating in Brazil. Here, we report the characterization of near full-length genome sequences (NFLG) of six phylogenetically related HIV-1 BF1 intersubtype recombinants (five from this study and one from other published sequences) representing CRF46_BF1. Initially, we selected 36 samples from 888 adult patients residing in São Paulo who had previously been diagnosed as being infected with subclade F1 based on pol subgenomic fragment sequencing. Proviral DNA integrated in peripheral blood mononuclear cells (PBMC) was amplified from the purified genomic DNA of all 36-blood samples by five overlapping PCR fragments followed by direct sequencing. Sequence data were obtained from the five fragments that showed identical genomic structure and phylogenetic trees were constructed and compared with previously published sequences. Genuine subclade F1 sequences and any other sequences that exhibited unique mosaic structures were omitted from further analysis Of the 36 samples analyzed, only six sequences, inferred from the pol region as subclade F1, displayed BF1 identical mosaic genomes with a single intersubtype breakpoint identified at the nef-U3 overlap (HXB2 position 9347-9365; LTR region). Five of these isolates formed a rigid cluster in phylogentic trees from different subclade F1 fragment regions, which we can now designate as CRF46_BF1. According to our estimate, the new CRF accounts for 0.56% of the HIV-1 circulating strains in São Paulo. Comparison with previously published sequences revealed an additional five isolates that share an identical mosaic structure with those reported in our study. Despite sharing a similar recombinant structure, only one sequence appeared to originate from the same CRF46_BF1 ancestor. We identified a new circulating recombinant form with a single intersubtype breakpoint identified at the nef-LTR U3 overlap and designated CRF46_BF1. Given the biological importance of the LTR U3 region, intersubtype recombination in this region could play an important role in HIV evolution with critical consequences for the development of efficient genetic vaccines.


Zinc deficiency induces hypertension by promoting renal Na+ reabsorption.
Zn2+ deficiency (ZnD) is a common comorbidity of many chronic diseases. In these settings, ZnD exacerbates hypertension. Whether ZnD alone is sufficient to alter blood pressure (BP) is unknown. To explore the role of Zn2+ in BP regulation, adult mice were fed a Zn2+-adequate (ZnA) or a Zn2+-deficient (ZnD) diet. A subset of ZnD mice were either returned to the ZnA diet or treated with hydrochlorothiazide (HCTZ), a Na+-Cl- cotransporter (NCC) inhibitor. To reduce intracellular Zn2+ in vitro, mouse distal convoluted tubule cells were cultured in N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN, a Zn2+ chelator)- or vehicle (DMSO)-containing medium. To replete intracellular Zn2+, TPEN-exposed cells were then cultured in Zn2+-supplemented medium. ZnD promoted a biphasic BP response, characterized by episodes of high BP. BP increases were accompanied by reduced renal Na+ excretion and NCC upregulation. These effects were reversed in Zn2+-replete mice. Likewise, HCTZ stimulated natriuresis and reversed BP increases. In vitro, Zn2+ depletion increased NCC expression. Furthermore, TPEN promoted NCC surface localization and Na+ uptake activity. Zn2+ repletion reversed TPEN effects on NCC. These data indicate that 1) Zn2+ contributes to BP regulation via modulation of renal Na+ transport, 2) renal NCC mediates ZnD-induced hypertension, and 3) NCC is a Zn2+-regulated transporter that is upregulated with ZnD. This study links dysregulated renal Na+ handling to ZnD-induced hypertension. Furthermore, NCC is identified as a novel mechanism by which Zn2+ regulates BP. Understanding the mechanisms of ZnD-induced BP dysregulation may have an important therapeutic impact on hypertension.


Heparin-Induced Allosteric Changes in SARS-CoV-2 Spike Protein Facilitate ACE2 Binding and Viral Entry.
Understanding the entry of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) into host cells is crucial in the battle against COVID-19. Using atomic force microscopy (AFM), we probed the interaction between the virus's spike protein and heparan sulfate (HS) as a potential attachment factor. Our AFM studies revealed a moderate-affinity interaction between the spike protein and HS on both model surfaces and living cells, highlighting HS's role in early viral attachment. Remarkably, we observed an interplay between HS and the host cell receptor angiotensin-converting enzyme 2 (ACE2), with HS engagement resulting in enhanced ACE2 binding and subsequent viral entry. Our research furthers our understanding of SARS-CoV-2 infection mechanisms and reveals potential interventions targeting viral entry. These insights are valuable as we navigate the evolving landscape of viral threats and seek effective strategies to combat emerging infectious diseases.


Retinal vascular reactivity to norepinephrine and angiotensin II in normals and diabetics.
Retinal arterial vasoconstriction induced by an infusion of angiotensin II or norepinephrine was investigated in eight normal controls (N), nine diabetics without retinopathy (DNR), and 10 diabetics with retinopathy (DR) by color fundus photographs taken before and after the infusions. Image analysis was done by a semiautomated computerized microdensitometer using a videoscanner. Normal controls and diabetics without retinopathy had a significant reduction in diameter compared with diabetics with retinopathy, who failed to constrict arterioles in response to either vasopressor. The mechanism of this phenomenon is unclear. Semiautomated computerized microdensitometry is reproducible and appears to be a sensitive technique to evaluate the vascular reactivity of the retinal vasculature.


Emergency Physician Practice Changes After Being Named in a Malpractice Claim.
Malpractice fear is a commonly cited cause for defensive medicine, but it is unclear whether being named in a malpractice claim changes physician practice patterns. We study whether there are changes in commonly used measures of emergency physician practice after being named in a malpractice claim. We performed a retrospective difference-in-differences study comparing practice patterns of emergency physicians named in a malpractice claim and unnamed matched controls working contemporaneously in the same emergency departments (EDs), using data from a national emergency medicine management group (59 EDs in 11 US states from 2010 to 2015). We studied aggregate measures of care intensity (hospital admission rate and relative value units/visit), studied care speed (relative value units/hour and discharged patients' length of stay), and assessed patient experience (monthly physician Press Ganey percentile rank). A total of 65 emergency physicians named in at least 1 malpractice claim and 140 matched controls met inclusion criteria. After the malpractice claim filing date, there were no significant changes in measures of care intensity or speed. However, named emergency physicians' patient experience scores improved immediately after the malpractice claim filing date and showed sustained improvements by 6.52 Press Ganey percentile ranks (95% confidence interval 0.67 to 12.38), with the increase most prominent among those involved in the 46 failure-to-diagnose claims (10.52; 95% confidence interval 3.72 to 17.32). We observed a temporal improvement in patient satisfaction scores for emergency physicians in this sample after their being named in a malpractice claim relative to matched controls. Measures of care intensity and speed did not significantly change.


Does Milk Consumption Contribute to Cardiometabolic Health and Overall Diet Quality?
Although milk consumption is recommended in most dietary guidelines around the world, its contribution to overall diet quality remains a matter of debate in the scientific community as well as in the public domain. This article summarizes the discussion among experts in the field on the place of milk in a balanced healthy diet. The evidence to date suggests at least a neutral effect of milk intake on health outcomes. The possibility that milk intake is simply a marker of diets higher in nutritional quality cannot be ruled out. This review also identifies a number of key research gaps pertaining to the impact of milk consumption on health. These need to be addressed to better inform future dietary guidelines.


Polyelectrolyte brushes in external fields: molecular dynamics simulations and mean-field theory.
A mean-field model is developed to predict the layer-thickness of sparse and salt-free polyelectrolyte brushes, exposed to an external electric field, which attracts the polyelectrolytes to the substrate. In molecular dynamics simulations, it is shown that a fraction of polymers collapses entirely to screen the charge of the substrate. The remaining brushes are then treated as field-free brushes at reduced grafting density. The mean-field model may thus be applied to field-free brushes, both in their osmotic and their weak charge regimes. It yields simple, closed equations for the brush height and for the partition of counterions in- and outside the brushes, and accurately reproduces simulation data of the collapse of the brushes during the crossover between both charge regimes.


Regulation of human GH receptor gene transcription by 20 and 22 kDa GH in a human hepatoma cell line.
The human GH gene is 1.7 kilobase pairs (kb) in length and is composed of five exons and four introns. This gene is expressed in the pituitary gland and encodes a 22 kDa protein. In addition to this predominant (75%) form, 5-10% of pituitary GH is present as a 20 kDa protein that has an amino acid (aa) sequence identical to the 22 kDa form except for a 15 aa internal deletion of residues 32-46 as a result of an alternative splicing event. Because it has been reported that non-22-kDa GH isoforms might be partly responsible for short stature and growth retardation in children, the aim of this study was to compare the impact of both 22 kDa and 20 kDa GH on GH receptor gene (GH receptor/GH binding protein (GHR/GHBP)) expression. Various concentrations of 20 kDa and 22 kDa GH (0, 2, 5, 12.5, 25, 50 and 150 ng/ml) were added to human hepatoma (HuH7) cells cultured in serum-free hormonally defined medium for 0, 1 and 2 h. Thereafter GHR/GHBP mRNA expression was measured by quantitative PCR. Addition of either 20 kDa or 22 kDa GH, at low or normal physiological concentrations (0, 2, 5, 12.5, 25 or 50 ng/ml) induced a dose-dependent increase in GHR/GHBP expression. However, a supraphysiological concentration of 20 kDa GH (150 ng/ml) resulted in a significantly lower (P<0.05) downregulation of GHR/GHBP gene transcription compared with the downregulation achieved by this concentration of 22 kDa GH. This difference might be explained by a decreased ability to form a 1 : 1 complex with GHR and/or GHBP, which normally occurs at high concentrations of GH. Nuclear run-on experiments and GHBP determinations confirmed the changes in GHR/GHBP mRNA levels. In conclusion, we report that both 20 kDa and 22 kDa GH, in low and normal physiological concentrations, have the same effect on regulation of GHR/GHBP gene transcription in a human hepatoma cell line. At a supraphysiological concentration of 150 ng/ml, however, 20 kDa GH has a less self-inhibitory effect than the 22 kDa form.


Use of graphene as protection film in biological environments.
Corrosion of metal in biomedical devices could cause serious health problems to patients. Currently ceramics coating materials used in metal implants can reduce corrosion to some extent with limitations. Here we proposed graphene as a biocompatible protective film for metal potentially for biomedical application. We confirmed graphene effectively inhibits Cu surface from corrosion in different biological aqueous environments. Results from cell viability tests suggested that graphene greatly eliminates the toxicity of Cu by inhibiting corrosion and reducing the concentration of Cu(2+) ions produced. We demonstrated that additional thiol derivatives assembled on graphene coated Cu surface can prominently enhance durability of sole graphene protection limited by the defects in graphene film. We also demonstrated that graphene coating reduced the immune response to metal in a clinical setting for the first time through the lymphocyte transformation test. Finally, an animal experiment showed the effective protection of graphene to Cu under in vivo condition. Our results open up the potential for using graphene coating to protect metal surface in biomedical application.


Inappropriate application of Yaşargil aneurysm clips: a new observation and technical remark.
Recurrences after complete surgical clipping of an aneurysm base are rare. We describe a potential reason for such recurrences: the inappropriate application of a popular aneurysm clip. We present 3 cases in which intraoperative indocyanine green video angiography after clipping clearly demonstrates filling of the aneurysm. During surgery, the necks of the aneurysms were clipped with Yaşargil aneurysm clips (Aesculap AG & Co., Tuttlingen, Germany) without any problems; however, indocyanine green video angiography after clipping showed filling of the aneurysms through the point located at the junction of the blade and spring portions of the clips. In the first patient, the aneurysm sac was further coagulated, and a second, smaller clip was applied to completely occlude the untreated part. In the second patient, the clip was replaced with a different clip that had longer blades. In the third patient, 2 additional clips were applied, and the aneurysm sac was also coagulated. The postoperative computed tomographic angiographic examinations showed total occlusion of the aneurysms and patency of the parent arteries. All patients achieved full recovery after the operations. We present here, for the first time, evidence that the small orifice located at the junction of the blade and spring portions of Yaşargil aneurysm clips can lead to failure of initial surgery and/or recurrence. This can be avoided by using clips with slightly longer blades to keep the orifice away from the aneurysm or by applying a second clip to occlude the untreated part.


Standardised packaging and new enlarged graphic health warnings for tobacco products in Australia-legislative requirements and implementation of the Tobacco Plain Packaging Act 2011 and the Competition and Consumer (Tobacco) Information Standard, 2011.
This paper describes the development, content and implementation of two pieces of Australian tobacco control legislation: one to standardise the packaging of tobacco products and the other to introduce new, enlarged graphic health warnings. It describes the process of legislative drafting, public consultation and parliamentary consideration. It summarises exactly how tobacco products have been required to look since late 2012. Finally, it describes implementation, most particularly, the extent to which packs compliant with the legislation became available to consumers over time.


Promotion and prevention focus on alternative hypotheses: implications for attributional functions.
Five studies examined hypothesis generation and discounting in causal attribution from the perspective of regulatory focus theory (E. T. Higgins, 1997, 1998). According to this theory, a promotion focus is associated with generating more and simultaneously endorsing multiple hypotheses, whereas a prevention focus is associated with generating only a few hypotheses and selecting 1 hypothesis from a given set. Five studies confirmed these predictions for both situationally induced and chronic individual differences in regulatory focus. In Studies 1, 2, and 3, individuals in a promotion focus generated more hypotheses than individuals in a prevention focus. In Studies 4 and 5, individuals in a promotion focus discounted explanations in light of alternatives less than individuals in a prevention focus. Study 5 also found that in a promotion focus, person explanations were generalized across situations less than in a prevention focus.


Internet-based treatment of gambling problems: A systematic review and meta-analysis of randomized controlled trials.
The effect of internet-based psychological treatment for gambling problems has not been previously investigated by meta-analysis. The present study is therefore a quantitative synthesis of studies on the effects of internet-based treatment for gambling problems. Given that effects may vary according to the presence of therapist support and control conditions, it was presumed that subgroup analyses would elucidate such effects. A systematic search with no time constraints was conducted in PsycINFO, MEDLINE, Web of Science, and the Cochrane Library. Two authors independently extracted data using a predefined form, including study quality assessment based on the Cochrane risk of bias tool. Effect sizes were calculated using random-effects models. Heterogeneity was indexed by Cochran's Q and the I 2 statistics. Publication bias was investigated using trim and fill. Thirteen studies were included in the analysis. Random effects models at post-treatment showed significant effects for general gambling symptoms (g = 0.73; 95% CI = 0.43-1.03), gambling frequency (g = 0.29; 95% CI = 0.14-0.45), and amount of money lost gambling (g = 0.19; 95% CI = 0.11-0.27). The corresponding findings at follow-up were g = 1.20 (95% CI = 0.79-1.61), g = 0.36 (95% CI = 0.12-0.60), and g = 0.20 (95% CI = 0.12-0.29) respectively. Subgroup analyses showed that for general gambling symptoms, studies with therapist support yield larger effects than studies without, both post-treatment and at follow-up. Additionally, on general gambling symptoms and gambling frequency, there were lower effect sizes for studies with a control group compared to studies without a control group at follow-up. Studies with higher baseline severity of gambling problems were associated with larger effect sizes at both posttreatment and follow-up than studies with more lenient inclusion criteria concerning gambling problems. Internet-based treatment has the potential to reach a large proportion of persons with gambling problems. Results of the meta-analysis suggest that such treatments hold promise as an effective approach. Future studies are encouraged to examine moderators of treatment outcomes, validate treatment effects cross-culturally, and investigate the effects of novel developments such as ecological momentary interventions.


The epidermis coordinates thermoresponsive growth through the phyB-PIF4-auxin pathway.
In plants, an elevation in ambient temperature induces adaptive morphological changes including elongated hypocotyls, which is predominantly regulated by a bHLH transcription factor, PIF4. Although PIF4 is expressed in all aerial tissues including the epidermis, mesophyll, and vascular bundle, its tissue-specific functions in thermomorphogenesis are not known. Here, we show that epidermis-specific expression of PIF4 induces constitutive long hypocotyls, while vasculature-specific expression of PIF4 has no effect on hypocotyl growth. RNA-Seq and qRT-PCR analyses reveal that auxin-responsive genes and growth-related genes are highly activated by epidermal, but not by vascular, PIF4. Additionally, inactivation of epidermal PIF4 or auxin signaling, and overexpression of epidermal phyB suppresses thermoresponsive growth, indicating that epidermal PIF4-auxin pathways are essential for the temperature responses. Further, we show that high temperatures increase both epidermal PIF4 transcription and the epidermal PIF4 DNA-binding ability. Taken together, our study demonstrates that the epidermis regulates thermoresponsive growth through the phyB-PIF4-auxin pathway.