Deviation scores: An innovative approach to interpreting cognitive test results for individuals with intellectual disabilities.
Students with Intellectual Disability undergo frequent cognitive testing. Testing with this population is limited by insensitivity to relative strengths and weaknesses due to floor effects. The study explored the utility of deviation scores via four case studies as a supplement to educational decision-making. Four students with Intellectual Disability completed cognitive testing. Deviation scores were calculated using age dependent raw z-score transformations to determine deviation from the standardization sample norms. The application of deviation scores highlighted true relative strengths and weaknesses for students with Intellectual Disability rather than documenting previously known deficits. The four cases studies illustrated where deviation scores could, or could not, add value above and beyond traditional scoring. Deviation scores can supplement placement and service decisions for students. Practical and psychometric considerations are reviewed. The findings highlight the usefulness of deviation scores in providing meaningful information to school- and clinic-based practitioners.


The effect of mindfulness-based psychoeducation on insight and medication adherence of schizophrenia patients.
This research was conducted to determine the effect of mindfulness based psychoeducation program on insight and medication adherence of schizophrenia patients. The study was conducted in a true experiment design with pre-test and post-test control groups. The study population consisted of 369 schizophrenic patients enrolled in Community Mental Health Centers located in Balıkesir and Eskişehir province centers. The sample consisted of 135 patients, 55 from experimental and 80 from control groups selected by randomized sampling. The data was collected between February and May 2016. The Descriptive Information Form, Beck Cognitive Insight Scale (BCIS) and Medication Adherence Rating Scale (MARS) were used. In the experimental group, the psychoeducation program was applied. Number, percentage, mean, standard deviation, chi-square, t-test in both dependent and independent groups, were used in the analysis of the data. The mean post-test score of the Beck Cognitive Insight Scale was 4.89 ± 6.05 in the experimental group, 1.68 ± 5.67 in the control group and the difference between the mean scores was statistically significant (p < 0.05). The mean post-test score of Medication Adherence Ratıng Scale was 1.76 ± 0.42 in the experimental group, 1.50 ± 0.50 in the control group and the difference between the mean scores was statistically significant (p < 0.05). It was determined that psychoeducation program was effective in increasing cognitive insight level and medication adherence of patients and can be used by nurses in addition to medication.


Interaction between longitudinal and circular muscle in intestine of cat.
1. Slow waves recorded from isolated longitudinal muscle averaged 13 mV and had slow rate of rise (0.04 V/sec) whereas when recorded from intact segments the amplitude averaged 27 mV and the rate of rise was more rapid (0.09 V/sec), often with a notch between the initial peak and the plateau. Membrane potentials of longitudinal muscle were similar in isolated and intact preparations (- 66 mV). Resting potentials of circular muscle averaged - 67 mV.2. Small bundles of circular muscle tested in the double sucrose gap produced activity, either spontaneously or in response to stimulation, which fell into three categories: fast spikes (50-200 msec duration), slow spikes (1-5 sec duration), and small graded responses. The duration of fast spikes could be increased severalfold by the addition of TEA; the graded responses were converted to full-sized spikes by TEA.3. Treatment of circular muscle with Ca-free Krebs solution eliminated spikes, and in intact preparations reduced the amplitude and rate of rise of slow waves and eliminated the notch on slow waves.4. Current-voltage curves of longitudinal muscle show delayed rectification in the depolarizing quadrant; similar curves of circular muscle show anomalous rectification, i.e. a region where a very small current causes a large voltage change.5. Non-polarized electrotonic coupling between longitudinal and circular layers indicates low-resistance pathways. Apparent space constants of longitudinal muscle are greater when attached to circular muscle than when isolated.6. It is concluded that small slow potentials originate rhythmically in longitudinal muscle, that these spread passively to circular muscle where a regenerative amplification occurs which depends on Ca conductance and the amplified slow waves spread back to the longitudinal layer. In the intact intestine pacemaking is, therefore, separate from propagation and the circular muscle provides the bulk of depolarizing current for propagation.


Ribonucleoprotein organization of eukaryotic RNA. XXX. Evidence that U1 small nuclear RNA is a ribonucleoprotein when base-paired with pre-messenger RNA in vivo.
U1 small nuclear RNA is thought to be involved in messenger RNA splicing by binding to complementary sequences in pre-mRNA. We have investigated intermolecular base-pairing between pre-mRNA (hnRNA) and U1 small nuclear RNA by psoralen crosslinking in situ, with emphasis on ribonucleoprotein structure. HeLa cells were pulse-labeled with [3H]uridine under conditions in which hnRNA is preferentially labeled. Isolated nuclei were treated with aminomethyltrioxsalen , which produces interstrand crosslinks at sites of base-pairing between hnRNA and U1 RNA. hnRNA-ribonucleoprotein (hnRNP) particles were isolated in sucrose gradients containing 50% formamide, to dissociate non-crosslinked U1 RNA, and then analyzed by immunoaffinity chromatography using a human autoantibody that is specific for the ribonucleoprotein form of U1 RNA (anti-U1 RNP). After psoralen crosslinking, pulse-labeled hnRNA in hnRNP particles reproducibly bound to anti-U1 RNP. The amount of hnRNA bound to anti-U1 RNP was reduced 80 to 85% when psoralen crosslinking of nuclei was omitted, or if the crosslinks between U1 RNA and hnRNA were photo-reversed prior to immunoaffinity chromatography. Analysis of the proteins bound to anti-U1 RNP after crosslink reversal revealed polypeptides having molecular weights similar to those previously described for U1 RNP. These proteins did not bind to control, non-immune human immunoglobulin G. These results indicate that the subset of nuclear U1 RNA that is base-paired with hnRNA at a given time in the cell is a ribonucleoprotein. This raises the possibility that these proteins, as well as U1 RNA itself, may participate in pre-mRNA splice site recognition by U1 RNP.


Technocratic economic governance and the politics of UK fiscal rules.
This exploration of UK fiscal rules and the establishment of an independent UK fiscal watchdog focuses on the practical enactment of rules-based fiscal policy to analyse the politics of technocratic economic governance. Analysing UK macroeconomic policy rules and their operation unearths numerous dimensions of the politics of technocratic fiscal policy-making. Firstly, policy rules are marshalled for partisan purposes. Secondly, a politics of economic ideas surrounds the invention, revision and interpretation of fiscal rules. Thirdly, technocratic economic governance entails a 'politics of method', selecting methodological approaches necessarily built on particular political economic assumptions. Finally, a 'politics of numbers' sees politicians cooking the books to present their economic record favourably against fiscal yardsticks. Successive governments have altered UK fiscal rules, informed by different political economic principles. The Office for Budget Responsibility (OBR) sees itself as a technocratic and apolitical institution, yet its operational work entails contrasting accounts of the economy and policy. The scale of discretion and judgement inherent in operating fiscal rules is under-appreciated. This article finds technocratic economic governance to be a much more social and political process than many advocates of economic rules-based policy acknowledge. It engenders new forms of distinctive fiscal politics within elite statecraft and expert technocracy.


The in vivo effects of tumour necrosis factor blockade on the early cell mediated immune events and syndrome expression in rat adjuvant arthritis.
Anti-TNF therapy is effective in rheumatoid arthritis (RA); however, its mechanisms of action are incompletely understood. T cell-driven mechanisms are thought to play an important role in RA and the effects of TNF blockade on these mechanisms are unclear. Adjuvant arthritis (AA) is a T cell dependent model of inflammatory arthritis. The aims of this study were to investigate the effects of TNF blockade on in vivo T cell cytokine expression and to clarify the role of TNF in the inguinal lymph nodes (ILN) in early arthritis. AA was induced in male DA rats. Rats received either 3 mg/kg or 10 mg/kg PEG sTNF-RI at days 0, 2 and 4 postinduction or 10 mg/kg anti-TNF antibody on day of arthritis induction. Control rats received either saline or normal sheep serum. Paw volume was assessed every 3-4 days. Rats were sacrificed on days 0, 6, 13 and 21 postinduction. Ankles were removed for quantitative radiology and histology. Synovium and ILN were removed for cell culture and to determine mRNA expression of cytokines using semiquantitative RT-PCR. TNF and IFN-gamma protein production was measured using a bioassay and an ELISA. TNF blockade did not suppress mRNA expression of T cell cytokines in the ILN of rats in the early phase of AA, suggesting ongoing T cell activity. TNF protein production by ILN cells in culture was reduced in PEG sTNF-RI treated rats, although mRNA expression was increased in the ILN prior to culture. Early administration of PEG sTNF-RI did not attenuate AA, in contrast to an anti-TNF antibody, which suppressed disease. A shorter half-life for the PEG sTNF-RI compared with the anti-TNF antibody or the development of anti-PEG sTNF-RI antibodies may account for these results.


Expression of the tissue inhibitor of metalloproteinase-3 by transplanted VSMCs modifies heart structure and function after myocardial infarction.
Extracellular matrix (ECM) remodelling is a critical aspect of cardiac remodelling following myocardial infarction. Tissue inhibitors of metalloproteinases (TIMPs) are physiological inhibitors of matrix metalloproteinases (MMPs) that degrade the ECM proteins. TIMP-3 is highly expressed in the heart and is markedly downregulated in patients with ischaemic cardiomyopathy. Cell-based gene therapy can enhance the effects of cell transplantation by temporally and spatially regulating the release of the gene product. The purpose of this study was to investigate the role of TIMP-3 gene-transfected vascular smooth muscle cells (VSMCs) in modifying heart structure and function in rats when transplanted 3days after myocardial infarction (MI). Anesthetised rats were subjected to coronary artery ligation followed 3days later by thoracotomy and transplantation of TIMP-3 gene-transfected VSMCs, untransfected VSMCs or medium injected directly into the ischaemic myocardium. We assessed left ventricular structure and function by echocardiography and morphometry, and measured the levels of myocardial matrix metalloproteinase-2 and -9 (MMP-2, MMP-9), TIMP-3 and tumour necrosis factor-α (TNF-α) at 4weeks post-myocardial infarction. Transplantation of TIMP-3 gene-transfected VSMCs and untransfected VSMCs significantly decreased scar expansion and ventricular dilatation 25days post-transplantation (4weeks after MI). MMPs and TNF-α levels were reduced in the transplantation groups when compared to the group that was given an injection of medium only. Transplantation of TIMP-3 gene-transfected VSMCs was more effective in preventing progressive cardiac dysfunction, ventricular dilatation and in reducing MMP-2, MMP-9 and TNF-α levels when compared to the transplantation of untransfected VSMCs. TIMP-3 gene transfection was associated with attenuated left ventricular dilation and recovery of systolic function after MI compared with the control. TIMP-3 transfection enhanced the effects of transplanted VSMCs in rats by inhibiting matrix degradation and inflammatory cytokine expression, leading to improved myocardial remodelling.


Epitope mapping of a blood-brain barrier crossing antibody targeting the cysteine-rich region of IGF1R using hydrogen-exchange mass spectrometry enabled by electrochemical reduction.
Pathologies of the central nervous system impact a significant portion of our population, and the delivery of therapeutics for effective treatment is challenging. The insulin-like growth factor-1 receptor (IGF1R) has emerged as a target for receptor-mediated transcytosis, a process by which antibodies are shuttled across the blood-brain barrier (BBB). Here, we describe the biophysical characterization of VHH-IR4, a BBB-crossing single-domain antibody (sdAb). Binding was confirmed by isothermal titration calorimetry and an epitope was highlighted by surface plasmon resonance that does not overlap with the IGF-1 binding site or other known BBB-crossing sdAbs. The epitope was mapped with a combination of linear peptide scanning and hydrogen-deuterium exchange mass spectrometry (HDX-MS). IGF1R is large and heavily disulphide bonded, and comprehensive HDX analysis was achieved only through the use of online electrochemical reduction coupled with a multiprotease approach, which identified an epitope for VHH-IR4 within the cysteine-rich region (CRR) of IGF1R spanning residues W244-G265. This is the first report of an sdAb binding the CRR. We show that VHH-IR4 inhibits ligand induced auto-phosphorylation of IGF1R and that this effect is mediated by downstream conformational effects. Our results will guide the selection of antibodies with improved trafficking and optimized IGF1R binding characteristics.


Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.
Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.


State of the art for motor function assessment tools in spinal muscular atrophy (SMA).
Spinal muscular atrophy (SMA) is a progressive disease characterized by a degeneration of the spinal cord motor neurons. Many clinical trials - planned, in progress, or completed - have chosen motor function as the primary or secondary outcome because motor function assessment tools appeared to be more reliable than quantitative muscle testing in monitoring the course of the disease. Reliable, valid, and responsive outcome measures are needed to be able to capture the effectiveness of the therapeutic approach during clinical trials. Medical staff involved in neuromuscular diseases is faced with increasing pressure regarding the complex issue of choosing the right outcome measure for the objectives they have to assess. This paper provides a narrative literature review of available and validated motor function assessment tools in SMA population based on SMA subtypes, age and ambulant status. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


[The effect of saccharose on the growth and structure of bone tissue].
The content of organic mineral components in bones was studied after substitution of 25 and 50% of carbohydrate energy value in rations for saccharose. It was established that saccharose stimulated the growth of experimental animals, this was attended by increased phosphomonoesterase-1 activity, epiphyseal cartilage thickening, hyperfunction of the growth zone and changes in the phosphorus-calcium metabolism.


Failure to replicate evoked potential observations suggesting corpus callosum dysfunction in schizophrenia.
Somatosensory potentials (SEPs) evoked by vibrotactile finger stimulation have been reported to be the same in both hemispheres in schizophrenics, whereas they are asymmetrical in normals, with the contralateral hemisphere leading the ipsilateral (Jones and Miller, 1981). These findings were taken to indicate that the corpus callosum is nonfunctional in schizophrenics. To attempt replication of these results, vibrotactile SEPs of 6 schizophrenics and 6 normal controls were recorded with both bipolar and monopolar derivations. Asymmetrical bipolar SEPs were obtained in both schizophrenics and controls; previous observations of schizophrenic-control differences were not replicated. Acceptable evidence of ipsilateral early SEPs was not obtained; the test procedure seems inappropriate for measuring callosal conduction time.


Studies of lectin binding to normal and neoplastic lymphoid tissues. I. Normal nodes and Hodgkin's disease.
Lectins are proteins which have the ability to interact specifically with carbohydrate residues of glycoproteins and other glycoconjugates. The staining patterns of 10 fluorescein conjugated lectins (F-Con A, F-LCA, F-RCA, F-WGA, F-PHA, F-PWM, F-LTA, F-SBA, F-PNA, F-DB) and a protease inhibitor (F-LA) have been studied in histological sections of 11 normal or reactive lymph nodes and 6 nodes and one skin biopsy involved by Hodgkin's disease. On the basis of the patterns of lectin binding, and current knowledge of their saccharide specificities, we found that within germinal centres there is an orderly carbohydrate rich extracellular matrix which contains a higher concentration of GlcNAc and terminal Gal residues than the surface membranes of component cells. This suggests active secretion rather than simple membrane shedding, and it is possible that this pericellular domain plays a part in the regulation of the proliferative response, or controls migration of lymphocytes in and out of the germinal centre. Lectin binding in Reed-Sternberg cells suggests that the huge nucleoli contain glycoconjugates of diverse structure, which may be linked with their failure to undergo cytokinesis.


The origin and early evolution of plants.
Plant (archaeplastid) evolution has transformed the biosphere, but we are only now beginning to learn how this took place through comparative genomics, phylogenetics, and the fossil record. This has illuminated the phylogeny of Archaeplastida, Viridiplantae, and Streptophyta, and has resolved the evolution of key characters, genes, and genomes - revealing that many key innovations evolved long before the clades with which they have been casually associated. Molecular clock analyses estimate that Streptophyta and Viridiplantae emerged in the late Mesoproterozoic to late Neoproterozoic, whereas Archaeplastida emerged in the late-mid Palaeoproterozoic. Together, these insights inform on the coevolution of plants and the Earth system that transformed ecology and global biogeochemical cycles, increased weathering, and precipitated snowball Earth events, during which they would have been key to oxygen production and net primary productivity (NPP).


Dual carbon isotope (δ13C and Δ14C) characterization of particulate organic carbon in the Geum and Seomjin estuaries, South Korea.
We investigated the source, composition, and reactivity of particulate organic carbon (POC) in two contrasting Korean estuary systems, a closed estuary (Geum) (i.e., with an estuary dam at the river mouth) and an open (Seomjin) estuary. A dual isotope (δ13CPOC and Δ14CPOC) approach was applied to surface water samples collected along a salinity gradient in August 2016. Our results indicate that phytoplankton-derived POC was the main contributor to the total POC pool in the reservoir of the Geum estuary, while terrestrial-derived POC predominated the upper Seomjin estuary. A simple binary mixing model using Δ14CPOC revealed a higher modern POC contribution (87-90%) in the Geum estuary reservoir than that (77%) of the upper Seomjin estuary. Accordingly, it appears that an estuary dam can alter the source and reactivity of POC in a reservoir, which can be transferred to the adjacent coastal ecosystem.


The respiratory effects of tramadol in children under halothane an anaesthesia.
In a randomised double-blind, placebo-controlled study, the respiratory effects of intravenous tramadol (1 mg or 2 mg.kg-1) were compared with intravenous pethidine 1 mg.kg-1 under halothane anaesthesia. Children, ASA 1-2 between 2 and 10 years, presenting for inguinal surgery were studied. Once a steady state for halothane was reached, baseline recordings of end-tidal carbon dioxide, oxygen saturation, respiratory rate, tidal volume, minute volume, blood pressure and pulse rate were recorded. Intravenous tramadol 1 mg.kg-1 (T1) or 2 mg.kg-1 (T2) or pethidine 1 mg.kg-1 (PE) or placebo (PL) was then given according to a computer-generated randomisation. Further sets of recordings were taken at 5-min intervals for 20 min prior to commencement of surgery. The rate of recovery was assessed according to Aldrete scoring and the time and need for further analgesia were noted. The postoperative pain intensity was scored by means of a five-point verbal rating scale hourly for 6 h. Eighty-eight children, 22 per group, were studied. The mean age, weight and height were similar in each group. There was a statistically significant difference between the maximum decrease in respiratory rate and increase in end-tidal carbon dioxide between group PE and groups T1/T2 (p < 0.001). Thirteen episodes of apnoea occurred in the PE group, 11 requiring naloxone. The mean respiratory rate was lowest 5 min after injection in all groups. There was a slow increase in respiratory rate until incision in groups T1 and T2. Respiratory rate remained almost unchanged in PL until incision. The decreases in respiratory rate were reflected by increases in end-tidal carbon dioxide, the highest being recorded in the PE group. A lower intensity of pain in the first 2 h was noted in the three opioid groups. During the first 6 h, the proportion of patients requiring a further dose of analgesia was highest in PL and lowest in T2. Tramadol appears safe for use in children.


Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics.
Cellular membrane fluidity is a critical modulator of cell adhesion and migration, prompting us to define the systematic landscape of lineage-specific cellular fluidity throughout differentiation. Here, we have unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny: (1) membrane rigidification precedes the exit from pluripotency, (2) membrane composition modulates activin signaling transmission, and (3) signatures are relatively germ layer specific presumably due to unique lipid compositions. By modulating variable lineage-specific fluidity, we developed a label-free "adhesion sorting (AdSort)" method with simple cultural manipulation, effectively eliminating pluripotent stem cells and purifying target population as a result of the over 1,150 of screened conditions combining compounds and matrices. These results underscore the important role of tunable membrane fluidity in influencing stem cell maintenance and differentiation that can be translated into lineage-specific cell purification strategy.


Correlation of slipped capital femoral epiphysis with disk degeneration.
Spinal osteoarthritis is greater in patients with known hip pathology secondary to alterations in spinopelvic geometry. To our knowledge, no study has investigated the long-term impact of slipped capital femoral epiphysis (SCFE) on the spine. To evaluate the relationship between SCFE and the presence of degenerative disk disease and facet arthrosis. An anatomic study of disk degeneration in cadaveric lumbar spines with SCFE. An observational study was performed on 25 cadaveric specimens with SCFE and 647 controls that were identified out of 3100 total cadaveric specimens in an osteological collection. The specimens were evaluated for disk degeneration and facet arthrosis at L1/2 to L5/S1 using the classification of Eubanks and colleagues. Linear regression analyses were then used to determine the relationship between SCFE and lumbar disk and facet degeneration at each level, correcting for confounding factors such as age, sex, and race. Linear regression demonstrated a significant association (P<0.01) that was found between SCFE and degenerative disk disease at all levels from L1/2 to L5/S1. In addition, a significant association (P<0.01) was found between SCFE and facet arthrosis at all levels from L1/2 to L5/S1. The findings of this study show a relationship between SCFE and lumbar disk degeneration and facet arthrosis. This relationship may prove useful in predicting the course of spinal osteoarthritis in patients with SCFE.


Continual Low-Dose Infusion of Sulfamidase Is Superior to Intermittent High-Dose Delivery in Ameliorating Neuropathology in the MPS IIIA Mouse Brain.
Mucopolysaccharidosis IIIA (MPS IIIA) is a neurodegenerative lysosomal storage disorder characterised by progressive loss of learned skills, sleep disturbance and behavioural problems. Reduced activity of lysosomal sulfamidase results in accumulation of heparan sulfate and secondary storage of glycolipids in the brain. Intra-cisternal sulfamidase infusions reduce disease-related neuropathology; however, repeated injections may subject patients to the risk of infection and tissue damage so alternative approaches are required. We undertook a proof-of-principle study comparing the ability of slow/continual or repeat/bolus infusion to ameliorate neuropathology in MPS IIIA mouse brain. Six-week-old MPS IIIA mice were implanted with subcutaneously located mini-osmotic pumps filled with recombinant human sulfamidase (rhSGSH) or vehicle, connected to lateral ventricle-directed cannulae. Pumps were replaced at 8 weeks of age. Additional MPS IIIA mice received intra-cisternal bolus infusions of the same amount of rhSGSH (or vehicle), at 6 and 8 weeks of age. Unaffected mice received vehicle via each strategy. All mice were euthanised at 10 weeks of age and the brain was harvested to assess the effect of treatment on neuropathology. Mice receiving pump-delivered rhSGSH exhibited highly significant reductions in lysosomal storage markers (lysosomal integral membrane protein-2, GM3 ganglioside and filipin-positive lipids) and neuroinflammation (isolectin B4-positive microglia, glial fibrillary acidic protein-positive astroglia). MPS IIIA mice receiving rhSGSH via bolus infusion displayed reductions in these markers, but the effectiveness of the strategy was inferior to that seen with slow/pump-based delivery. Continual low-dose infusion may therefore be a more effective strategy for enzyme delivery in MPS IIIA.


Experimental etch-and-rinse adhesive systems containing MMP-inhibitors: Physicochemical characterization and resin-dentin bonding stability.
To evaluate the degree of conversion (DC%), water sorption (WS), solubility (SO) and the resin-dentin bonding stability (μTBS) of experimental (EXP) etch-and-rinse adhesive systems containing MMP-inhibitors: Galardin-GAL, Batimastat-BAT, GM1489-GM1 and chlorhexidine diacetate-CHX. DC% was measured using FT-IR spectroscopy, while WS and SO were calculated based on ISO4049. Thirty-six human molars were wet ground until the occlusal dentin was exposed. The adhesive systems were applied and resin composite buildups were incrementally constructed. After 24 h immersion in distilled water at 37 °C, the specimens were cut into resin-dentin beams with a cross-sectional area of 1 mm(2). The μTBS was evaluated after 24 h, 6 months and 12 months of water storage at 37 °C. Adper Single Bond 2 (SB2) was used as a commercial control. The data were analyzed using ANOVA and Tukey's HSD test. SB2 presented the highest DC% (p<0.05). CHX presented the lowest WS (p<0.05). GM1, GAL and BAT presented similar WS when compared with SB2 (p>0.05). SO was found to be not significant (p>0.05). All adhesive systems maintained μTBS stability after 6 months of water storage. Only BAT, GM1 and CHX maintained μTBs stability after 12 months of water storage. The experimental adhesive systems with GM1489 and chlorhexidine diacetate presented the best physicochemical properties and preserved resin-dentin bonding stability after 12 months of water storage. GM1489 could be suitable for inclusion as an MMP-inhibitor in etch-and-rinse adhesive systems to maintain resin-dentin bonding stability over time.


Dietary supplement use in a randomly selected group of elderly Australians. Results from a large nutrition and health survey.
The prevalence of dietary supplementation and its relationship to health and dietary habits was investigated in a random mail survey of 2,195 people aged 65 years and over in Adelaide, South Australia. Subjects were selected from the electoral rolls in an urban area, and 77% returned completed survey instruments. Thirty-five percent of men and 46% of women reported taking some form of supplement at least once a week regularly throughout the year (these are defined as "regular" supplementers). The most popular supplements (in descending order of popularity for the total group) were: unprocessed bran, wheatgerm, vitamin C, and multivitamins or minerals. Thirteen percent of men and 15% of women reported the use of supplements on an occasional basis (once every few months or "now and then")--these are defined as "irregular" or "occasional" supplementers. Supplement users did not differ from non-supplementers in their use of medical facilities or in the number of bouts of minor illness they had experienced in the preceding year. Regular supplement users had more favorable dietary habits and higher intakes of several vitamins, minerals, trace elements and fiber than either non-supplementers or occasional supplementers.


Myotherapy student clinical placements: A review beyond the teaching clinic.
Student clinical placements can offer an enriching learning experience, better preparing "work ready" graduates; however, it is unknown whether the type of clinical placement undertaken impacts the learning experience. Myotherapy degrees differ in their clinical practicum units, dependant on the undergraduate program they have enrolled in to. External clinical placements are common in allied health professional qualifications, offering industry experience and professional development. The purpose of this literature review is to examine allied health placement models, identify dominant theories, best practice, advantages and disadvantages of external clinical placements. This paper discusses current clinical placements offered within the myotherapy undergraduate degrees, as well as exploring other allied health professions. The review of other allied health professions may act as potential exemplars to develop an understanding of best practice around student clinical placements and how this can translate into improvements of existing myotherapy teaching programs. This summary may be useful to warrant further research into the development of myotherapy clinical education.


Velocity field and cavity dynamics in drop impact experiments.
Drop impact experiments allow to model a wide variety of natural processes, from raindrop impacts to planetary impact craters. In particular, interpreting the consequences of the planetary impacts requires an accurate description of the flow associated with the cratering process. In our experiments, we release a liquid drop above a deep liquid pool to investigate simultaneously the dynamics of the cavity and the velocity field produced around the air-liquid interface. Using particle image velocimetry, we analyse quantitatively the velocity field using a shifted Legendre polynomials decomposition. We show that the velocity field is more complex than considered in previous models, in relation to the non-hemispherical shape of the crater. In particular, the velocity field is dominated by the degrees 0 and 1, with contributions from the degree 2, and is independent of the Froude and the Weber number when these numbers are large enough. We then derive a semi-analytical model based on the Legendre polynomials expansion of an unsteady Bernoulli equation coupled with a kinematic boundary condition at the crater boundary. This model explains the experimental observations and can predict the time evolution of both the velocity field and the shape of the crater, including the initiation of the central jet.


Berberine ameliorates lipopolysaccharide‑induced inflammatory responses in mouse inner medullary collecting duct‑3 cells by downregulation of NF‑κB pathway.
The major role of inner medullary collecting duct (IMCD) cells is to maintain water and sodium homeostasis. In addition to the major role, it also participates in the protection of renal and systemic inflammation. Although IMCD cells could take part in renal and systemic inflammation, investigations on renal inflammation in IMCD cells have rarely been reported. Although berberine (BBR) has been reported to show diverse pharmacological effects, its anti‑inflammatory and protective effects on IMCD cells have not been studied. Therefore, in the present study, we examined the anti‑inflammatory and protective effects of BBR in mouse IMCD‑3 (mIMCD‑3) cells against lipopolysaccharide (LPS). An MTT assay was carried out to investigate the toxicity of BBR on mIMCD‑3 cells. Reverse transcription quantitative‑PCR and western blotting were performed to analysis pro‑inflammatory molecules and cytokines. Mechanisms of BBR were examined by western blotting and immunocytochemistry. According to previous studies, pro‑inflammatory molecules, such as inducible nitric oxide synthase and cyclooxygenase‑2, and pro‑inflammatory cytokines, such as interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α are increased in LPS‑exposed mIMCD‑3 cells. However, the production of these pro‑inflammatory molecules is significantly inhibited by treatment with BBR. In addition, BBR inhibited translocation of nuclear factor (NF)‑κB p65 from the cytosol to the nucleus, and degradation of inhibitory κ‑Bα in LPS‑exposed mIMCD‑3 cells. In conclusion, BBR could inhibit renal inflammatory responses via inhibition of NF‑κB signaling and ultimately contribute to amelioration of renal injury during systemic inflammation.


Eyes open versus eyes closed: effect on human rotational responses.
The effect of eyelid closure on the response to rotational vestibular stimulation was assessed by evaluating 16 normal human subjects with both earth vertical axis (EVA) and earth horizontal axis (EHA) yaw rotations with either eyes closed (EC) or eyes open in the dark (EOD). Results indicated that for EVA rotation, the subjects' responses were of larger magnitude and less variable with EOD than with EC. However, for EHA rotation, responses were of larger magnitude and equally variable with EC as compared to EOD. Our data also indicated that the quality of the EHA response with EC was altered because eyelid closure influenced the amount of periodic gaze. We conclude that eyelid closure has an effect upon both canalocular and otolithocular reflexes and suggest that both EVA and EHA rotational testing be performed with EOD rather than with EC.


Leydig cell tumour of the testis: presentation of two cases.
Two cases of Leydig cell tumour of the testis with no hormonal and metastatic manifestations are presented. Clinical features of the disease are discussed.


Transcriptional regulation of human thyroid hormone receptor beta 1 gene expression: effect of human retinoid X receptor and identification of a transcriptional silencer region.
Effects of human retinoid X receptor alpha (hRXR alpha) and its ligand, 9-cis-retinoic acid, on T3-mediated auto-regulation of hTR beta 1 gene expression were examined using a chloramphenicol acetyltransferase (CAT) reporter system, and a deletional analysis of the promoter. hRXR alpha enhanced T3-dependent CAT induction mediated through the proximal (p) TRE in a ligand (9-cis-retinoic acid) independent manner. In a gel mobility shift assay, hRXR alpha enhanced the binding of hTR beta 1 to the pTRE by the formation of hRXR alpha-hTR beta 1 heterodimers. On the other hand, hRXR alpha and 9-cis-retinoic acid did not show any effects on T3-dependent CAT induction mediated through the distal (d) TRE or the binding of hTR beta 1 to the dTRE. A four hundred-base pair (bp) fragment adjacent upstream of the dTRE showed a T3 independent suppressor effect on the function of the pTRE and dTRE. Thus, this region may be an important regulator of the T3 dependent up-regulation of the TR beta 1 gene expression which is observed only under specific conditions.


Outcomes with temporary mechanical circulatory support before minimally invasive centrifugal left ventricular assist device.
Despite improved survival and morbidity after durable left ventricular assist device (dLVAD), outcomes for cardiogenic shock patients are suboptimal. Temporary mechanical circulatory support (tMCS) can permit optimization before dLVAD. Excellent outcomes have been observed using minimally-invasive dLVAD implantation. However, some feel tMCS contraindicates this approach. To evaluate whether left thoracotomy/hemisternotomy (LTHS) dLVAD placement is safe in this setting, we compared patients who did and did not require tMCS. Outcomes for patients receiving dLVADs via LTHS were compared among those bridged with extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or no tMCS. We evaluated demographics, comorbidities, laboratory and hemodynamic data, and intraoperative and postoperative outcomes. Eighty-three patients underwent LTHS dLVAD placement. Fifty did not require tMCS, while 22 (26%) required IABP, and 11 (13%) ECMO. Non-tMCS patients were primarily Intermacs 3 (56%), while IABP recipients were mainly Intermacs 2 (45%). All patients with ECMO were Intermacs 1. Patients with tMCS had worse end-organ function. Operative outcomes were similar except more concomitant procedures and red-cell transfusions in patients with ECMO. Intensive care unit and hospital length of stay and inotrope duration were also similar. There were no differences in bleeding, stroke, and infection rates. Three- and 12-month survival were: no tMCS: 94%, 86%; IABP: 100%, 88%; and ECMO: 81%, 81% (P = .45). Patients with cardiogenic shock can safely undergo LTHS dLVAD implantation after stabilization with ECMO or IABP. Outcomes and complications in these patients were comparable to a less severely ill cohort without tMCS.


S-100 protein stimulates cellular proliferation.
S-100 protein (S-100p) is a small, acidic, calcium-binding protein that is present (predominantly) in the cytoplasm of many types of cells including those of neuroectodermal origin, such as glial cells, schwann cells and melanocytes. In human melanoma cells S-100p is abundant relative to the small quantities expressed by normal melanocytes. We investigated the possibility that this protein may be a growth factor. Purified S-100p from bovine brain or human melanoma cells was added exogenously to human melanoma cells and peripheral blood lymphocytes (PBL) and their growth in the presence of different concentrations of S-100p was determined using a [3H]dT-uptake proliferation assay. The growth of melanoma cells was stimulated by S-100p at concentrations of 1.95-31.25 micrograms/ml. Slight inhibition of cell proliferation occurred at high concentrations (125 micrograms/ml). Maximum stimulation of PBL was at 31.25 micrograms/ml. PBL were not inhibited even at high concentrations of S-100p (125 micrograms/ml). PBL stimulation by S-100p did not require the presence of monocytes/macrophages. Though stimulation by S-100p is not restricted to a specific cell type, when released by melanoma cells it may function as an "autocrine" tumor growth factor. Other cells, such as PBL, coming in contact with S-100p are also stimulated to proliferate.


Effect of Linker Length and Flexibility on the Clostridium thermocellum Esterase Displayed on Bacillus subtilis Spores.
In fusion protein design strategies, the flexibility and length of linkers are important parameters affecting the bioactivity of multifunctional proteins. A series of fusion proteins with different linkers were constructed. The effect of temperature, pH, and organic solvents was investigated on the enzymatic activity. Fusion proteins with P1(PTPTPT) and P2((PTPTPT)2) linkers remained highly active with wide temperature range. At pH 9.6, the relative activity of fusion proteins with (PTPTPT)2 and S2(EGKSSGSGSESKST) linkers was 70 and 62 % (1.75 and 1.5 times of that of non-linker ones). Fusion proteins with S3((GGGGS)4) linker retained 55 % activity after 5 h of incubation at 80 °C (1.2-fold of that of non-linker fusion proteins and 1.9-fold of GGGGS-linker fusion proteins). Finally, the relative activity of fusion proteins having different linkers was increased with 20 % dimethyl sulfoxide (DMSO) and methanol; relative activity of fusion proteins with EGKSSGSGSESKST linkers was enhanced 1.5- and 2.2-fold, respectively. These results suggest that longer flexible linker can enhance the activity and stability of displayed esterase than shorter flexible linker. Optimizing peptide linkers with length, flexibility, and amino acid composition could improve the thermostability and activity of the displayed enzyme.


New low energy transvenous cardioverting and pacing electrode.
A new endocardial catheter electrode (Medtronic model 6880) is described which can be used for ventricular pacing and for intracavitary cardioversion and defibrillation. Initial results in dogs and preliminary clinical trials in humans indicate that this catheter will extend the usefulness of electrical stimulation therapy for treatment of life-threatening tachyarrhythmias.


Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.
Mendelian disorders are most commonly caused by mutations identifiable by DNA sequencing. Exonic deletions and duplications can go undetected by sequencing, and their frequency in most Mendelian disorders is unknown. We designed an array comparative genomic hybridization (CGH) test with probes in exonic regions of 589 genes. Targeted testing was performed for 219 genes in 3,018 patients. We demonstrate for the first time the utility of exon-level array CGH in a large clinical cohort by testing for 136 autosomal dominant, 53 autosomal recessive, and 30 X-linked disorders. Overall, 98 deletions and two duplications were identified in 53 genes, corresponding to a detection rate of 3.3%. Approximately 40% of positive findings were deletions of only one or two exons. A high frequency of deletions was observed for several autosomal dominant disorders, with a detection rate of 2.9%. For autosomal recessive disorders, array CGH was usually performed after a single mutation was identified by sequencing. Among 138 individuals tested for recessive disorders, 10.1% had intragenic deletions. For X-linked disorders, 3.5% of 313 patients carried a deletion or duplication. Our results demonstrate that exon-level array CGH provides a robust option for intragenic copy number analysis and should routinely supplement sequence analysis for Mendelian disorders.


Thrombolytic therapy in acute myocardial infarction: Part I.
Thrombolytic therapy with pharmacologic agents is an exciting approach to the treatment of myocardial infarction. The results of several clinical studies indicate that perfusion can be restored with intravenous therapy and may be associated with a reduction in infarct size and improved left ventricular function. In a trial involving more than 11,000 patients, thrombolytic therapy reduced acute and long term mortality. Pharmacologic thrombolysis, however, is not without problems. When administered intravenously, the agents currently available, streptokinase and urokinase, are associated with a relatively low recanalization rate as well as a risk of adverse effects, most commonly a systemic lytic state and risk of bleeding complications. Although intracoronary administration is associated with a higher rate of recanalization, the need for cardiac catheterization limits its applicability and results in a delay in the initiation of thrombolytic therapy (which diminishes salvage of myocardium). The trials assessing the existing agents have shown that time is a critical variable in the success of thrombolytic therapy. This had led investigators to focus more attention on intravenous agents that can be administered rapidly. The newer agents now under investigation, acylated streptokinase and single-chain urokinase, may represent improvements of currently available products and may offer potentially increased benefits. A fibrinogen-sparing agent, such as t-PA, in addition to being highly effective, may offer advantages through minimizing the systemic lytic effect. Additional randomized, controlled clinical trials currently are underway to determine the effect on mortality of this "fibrinolytic" therapy as part of a total treatment regimen. The current status of our knowledge concerning thrombolytic therapy in acute myocardial infarction can be summarized as follows: 1. Transmural (that is, Q wave) myocardial infarction usually is caused by an obstructing coronary thrombus. 2. The thrombus can be lysed with intravenous therapy in the majority of cases, particularly with newer, well-tolerated fibrin-specific agents. 3. There is considerable evidence suggesting that reperfusion reduces the acute morbidity and mortality when therapy is administered successfully within the initial 3 to 4 hours (and possibly up to 6 hours) after onset of symptoms. 4. Data on long term prognosis after thrombolysis are very encouraging, although limited. 5. Conventional agents lead to significant fibrinogen depletion and therefore an increased risk of bleeding; the new fibrin-selected agents cause less fibrinogen degradation and may reduce the risk of hemorrhagic complications.(ABSTRACT TRUNCATED AT 400 WORDS)


Polymorphism T→C of gene CYP17 promoter and polycystic ovary syndrome risk: a meta-analysis.
The T→C polymorphism of CYP17 gene has been inconsistently associated with polycystic ovary syndrome (PCOS) risk. We examined the association by performing a meta-analysis. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP17 polymorphism and PCOS were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (CC vs. TT, TC vs. TT), dominant model (CC+TC vs. TT), and recessive model (CC vs. TC+TT). Subgroup analyses were performed by ethnicity, country, Hardy-Weinberg equilibrium (HWE) in controls and study sample size. This meta-analysis included 10 case-control studies, which included 1321 PCOS cases and 1017 controls. Overall, the variant genotypes (CC and TC) were not associated with PCOS risk, compared with the wild-type TT homozygote. Similarly, no associations were found in the dominant and recessive models. Stratified analyses by ethnicity/country also detected no significant association. However, limiting the analysis to the studies within HWE, a significantly increased risk was observed (TC vs. TT, OR=1.44, 95% CI=1.10-1.88; dominant model, OR=1.41, 95% CI=1.10-1.81). Moreover, when stratifying by study sample size, a significantly elevated risk was found among small sample studies (≤200 subjects), but not among large sample studies (> 200 subjects). This meta-analysis suggests that the CYP17 T/C polymorphism may be not associated with PCOS risk, while the observed increase in risk of PCOS may be due to small-study bias.


Evaluation of eazyplex® SuperBug CRE Test for Beta-Lactamase Genes Detection in Klebsiella spp. and P. aeruginosa Strains.
The multi-drug resistance of Gram-negative rods is one of the most important issues of present medicine. In recent years, more and more strains resistant to the majority or to all possible therapeutic options have been isolated-especially Klebsiella spp. and Pseudomonas spp. representatives. It is very important to detect strains with these phenotypes as quickly and reliably as possible. The aim of the study was to evaluate the usefulness of eazyplex® SuperBug CRE test (Amplex Diagnostics) for the detection of the most important beta-lactam resistance genes. eazyplex® SuperBug CRE test is based on the loop-mediated isothermal amplification (LAMP) method, and detects genes for the following beta-lactamases: KPC, NDM-1, VIM, OXA-48, CTX-M1, CTX-M9 and OXA-181. The study involved 87 strains. For all of the positive strains in the LAMP method, additional PCR were performed to increase the spectrum of ESBLs detected by the genes encoding for enzymes belonging to TEM and SHV families. The results obtained by the tested method and standard PCR were consistent for all Klebsiella spp. strains. The discrepancy between the evaluated test and PCR results was observed for one P. aeruginosa strain. The eazyplex® SuperBug CRE test can be used for quick detection of the most important beta-lactam resistance mechanisms amongst Gram-negative rods.


Common juniper, an overlooked conifer with high invasion potential in protected areas of Patagonia.
The benefits of early detection of biological invasions are widely recognized, especially for protected areas (PAs). However, research on incipient invasive plant species is scarce compared to species with a recognized history of invasion. Here, we characterized the invasion status of the non-native conifer Juniperus communis in PAs and interface areas of Andean Patagonia, Argentina. We mapped its distribution and described both the invasion and the environments this species inhabits through field studies, a literature review, and a citizen science initiative. We also modeled the species' potential distribution by comparing the climatic characteristics of its native range with those of the introduced ranges studied. The results show that J. communis is now widely distributed in the region, occurring naturally in diverse habitats, and frequently within and close to PAs. This species can be considered an incipient invader with a high potential for expansion in its regional distribution range, largely due to its high reproductive potential and the high habitat suitability of this environment. Early detection of a plant invasion affords a valuable opportunity to inform citizens of the potential risks to high conservation value ecosystems before the invader is perceived as a natural component of the landscape.


A 13-week subchronic toxicity study of paprika color in F344 rats.
The fruit of the paprika (Capsicum annuum) has been widely used in various countries as a spice and food-coloring additive. As a part of the safety assessment of paprika color (Paprika oleoresin), a 13-week subchronic toxicity study was performed in F344 rats. To establish a no-observed-adverse-effect level (NOAEL) for application in subsequent long-term studies, rats were fed powder diet containing paprika color at dose levels of 0 (basal diet), 0.62, 1.25, 2.5 and 5% (maximum) for 13 weeks. During the experiment, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. Although serum total cholesterol was dose-dependently increased in both sexes, no related histopathological changes were observed in the liver. Slight inflammatory cell infiltration in the myocardium and vacuolation of hepatocytes were noted in both control and paprika color-treated animals, but there were no clear differences between groups. In conclusion, paprika color even at 5% in the diet (0.67 g/rat/day or 2948.4 mg/kg bw/day for male rats and 0.43 g/rat/day or 3197.4 mg/kg bw/day for female rats) did not cause remarkable adverse effects in F344 rats. Thus, the NOAEL and the maximum dose level for carcinogenicity testing of paprika color were concluded to be 5% in the diet.


Evaluation of the Datascope ACCUSAT pulse oximeter in healthy adults.
Arterial hemoglobin oxygen saturation measured with the Datascope ACCUSAT pulse oximeter was compared with simultaneous arterial hemoglobin oxygen saturation measurements in healthy adult volunteers. One hundred thirty-five arterial blood samples ranging in saturation from 63 to 100% were obtained from 15 adults, aged 20 to 43 years. These subjects had different skin pigmentation, hematocrit, and smoking habits. Steady-state hypoxia was achieved by varying the inspired oxygen concentration between 10 and 21%. Readings from the Datascope ACCUSAT pulse oximeter and the Hewlett-Packard 47201A ear oximeter were compared with arterial blood samples analyzed by the Instrumentation Laboratories IL 282 in vitro CO-Oximeter. The equation for the best fitted linear regression line between the ACCUSAT pulse oximeter and the reference IL 282 CO-Oximeter was: ACCUSAT = 1.08(IL) - 6.86. The linear regression analysis revealed a high degree of correlation (r = 0.99), and a small standard error of the estimate (SEE = 1.29%). Simultaneous comparisons between arterial hemoglobin oxygen saturation measured with the ACCUSAT pulse oximeter and the Hewlett-Packard ear oximeter also showed a close correlation (r = 0.99, SEE = 1.47%). A similar comparison between the ACCUSAT and the Ohmeda 3700 pulse oximeter revealed good correlation (r = 0.99, SEE = 1.72%). We found that the ACCUSAT pulse oximeter is an accurate instrument for measuring arterial hemoglobin oxygen saturation noninvasively in the range between 60 and 100%.


Topical cidofovir (HPMPC) is an effective adjuvant to surgical treatment of anogenital condylomata acuminata.
Human papilloma virus infections of the anogenital region are very common and cause condylomata acuminata; cervical, penile, vulvar, or perianal intraepithelial neoplasia; and more rarely, invasive cancer. The currently available therapies often result in painful, extensive, slow-healing ulcerations and frequent early relapses. This study was aimed at determining the efficacy of topical application of the antiviral agent cidofovir at 1 percent. Twenty patients treated with coagulations were compared with 27 patients treated with cidofovir. Lesions refractory to cidofovir were cleared up with additional coagulations. The number of patients previously treated for condylomata did not differ between the two groups. Significantly more patients treated with cidofovir, however, had an impaired immune status (37 percent) compared with the patients treated with coagulations (5 percent). Cidofovir alone cured the lesions in 32 percent of the patients and induced partial regression in 60 percent. However, in smokers, complete resolution of the condylomata occurred only in 16.6 percent compared with 66 percent of nonsmokers (P = 0.03). The number of coagulation sessions was much lower (P < 0.0005) in the cidofovir treated group (1 +/- 0.8 vs. 2.9 +/- 2). Furthermore, the relapse rate was significantly lower in the cidofovir group (3.7 vs. 55). All recurrences in the electrocoagulation group occurred within four months of confirmed lesion clearance. Topical applications of cidofovir 1 percent were well tolerated. Thirty-three percent of the patients reported only mild pain caused by erosive dermatitis. In contrast, coagulations caused painful ulcerations that necessitated the use of analgesics in all patients treated this way. Topical applications of cidofovir, an antiviral compound with activity against human papilloma virus, is effective in the majority of patients with perianal condylomata and is a valuable adjuvant to surgical treatment of these lesions.


Decreasing delays in urgent and expedited surgery in a university teaching hospital through audit and communication between peri-operative and surgical directorates.
National Confidential Enquiry into Patient Outcome and Death guidelines for urgent surgery recommend a fully staffed emergency operating theatre and restriction of 'after-midnight' operating to immediate life-, limb- or organ-threatening conditions. Audit performed in our institution demonstrated significant decreases in waiting times for urgent surgery and an increased seniority of medical care associated with overnight pre-operative assessment of patients by anaesthetic trainees. Nevertheless, urgent cases continued to be delayed unnecessarily. A classification of delays was developed from existing guidelines and their incidence was audited. The results were disseminated to involved directorates. A repeat of the audit demonstrated a significant decrease in delays (p = 0.001), a significant increase in the availability of surgeons (p = 0.001) and a significant decrease in the median waiting time for urgent surgery compared to the first audit cycle and a previous standard (p < 0.01). We conclude that auditing delays and disseminating the results of the audit significantly decreases delays and median waiting times for urgent surgery because of improved surgical availability.


Synthesis of chiral 2-(4-phenoxyphenylsulfonylmethyl)thiiranes as selective gelatinase inhibitors.
[reactions: see text] Compound 1, 2-(4-phenoxyphenylsulfonylmethyl)thiirane, is a selective inhibitor of gelatinases, which is showing high promise in studies of animal models for cancer metastasis and stroke. The (R)-1 and (S)-1 enantiomers of compound 1 were each synthesized in this study and were shown to be equally active in inhibition of gelatinases.


Relationship between regional pertechnetate cerebral circulation time and EEG in patients with cerebral infarction.
The qualitative and regional correlations between the EEG and the cerebral circulation time (CCT), obtained by using intravenously injected pertechnetate and a multidetector device, were studied in 75 patients with supratentorial cerebral infarction. Because bolus dispersion and changes in systemic circulation may distort absolute CCT values when intravenous injection of the isotope is used, the inter- and intrahemispheric relative CCT values were used as indices of CCT. Overall good correlations could be demonstrated between both inter- and intrahemispheric CCT abnormalities and the EEG, though not in all patients. The number of patients with pathological CCT findings showed a tendency to increase with increasing severity of the EEG abnormality. The number of abnormal CCT areas per patient (indicating the size of the circulation disturbance) also increased significantly with increasing severity of the EEG disturbance. Interestingly, relative 'hypervelocity' areas occurred in fewer patients with normal or clearly disturbed EEGs than in patients with mildly disturbed EEGs, perhaps due to differences in autoregulatory capacity and collateral circulation. Within the EEG focus the relative number of CCT abnormalities was greater than outside it. In spite of this fairly good overall correlation between the EEG focus and the CCT abnormality, more than 10% of the patients with an EEG focus showed no CCT abnormalities, thus indicating the complementary roles of these methods. The present study on cerebral infarction, though using intravenously injected pertechnetate for the CCT measurement, showed a reasonable correspondence with earlier reports on the relationship between the EEG and either the CBF or the CCT (obtained by intra-arterially injected isotope). This would seem to suggest that the used non-invasive method for regional CCT measurement has potential for evaluation of cerebral haemodynamics.


Brain and central haemodynamics and oxygenation during maximal exercise in humans.
During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O(2) delivery and uptake. Here, we examined whether the uptake of O(2) and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O(2) delivery is related to declining venous return. We measured brain and central haemodynamics and oxygenation in healthy males (n= 13 in 2 studies) performing intense cycling exercise (360 +/- 10 W; mean +/-s.e.m.) to exhaustion starting with either high (H) or normal (control, C) body temperature. Time to exhaustion was shorter in H than in C (5.8 +/- 0.2 versus 7.5 +/- 0.4 min, P < 0.05), despite heart rate reaching similar maximal values. During the first 90 s of both trials, frontal cortex tissue oxygenation and the arterial-internal jugular venous differences (a-v diff) for O(2) and glucose did not change, whereas middle cerebral artery mean flow velocity (MCA V(mean)) and cardiac output increased by approximately 22 and approximately 115%, respectively. Thereafter, brain extraction of O(2), glucose and lactate increased by approximately 45, approximately 55 and approximately 95%, respectively, while frontal cortex tissue oxygenation, MCA V(mean) and cardiac output declined approximately 40, approximately 15 and approximately 10%, respectively. At exhaustion in both trials, systemic VO(2) declined in parallel with a similar fall in stroke volume and central venous pressure; yet the brain uptake of O(2), glucose and lactate increased. In conclusion, the reduction in stroke volume, which underlies the fall in systemic O(2) delivery and uptake before exhaustion, is partly related to reductions in venous return to the heart. Furthermore, fatigue during maximal exercise, with or without heat stress, in healthy humans is associated with an enhanced rather than impaired brain uptake of O(2) and substrates.


Conviction Narrative Theory gains from a richer formal model.
Conviction Narrative Theory (CNT) is a convincing descriptive theory, and Johnson et al.'s formal model is a welcome contribution to building more precise, testable hypotheses. However, some extensions to the proposed model would make it better defined and more powerful. The suggested extensions enable the model to go beyond CNT, predicting choice outcomes and explaining affective phenomena.


Rapid quantitative capillary zone electrophoresis method for monitoring the micro-heterogeneity of an intact recombinant glycoprotein.
A simple high-resolution capillary zone electrophoresis (CZE) method capable of rapidly assessing the micro-heterogeneity of a 24 kDa molecular weight glycoprotein, has been developed. Separation is carried out using a bare silica capillary at a pH of 2.5 in a commercially available electrophoresis buffer system composed of triethanolamine and phosphoric acid. Over 30 peaks were detected within a run time of 15 min using a 27 cm capillary and approximately 60 peaks were detected using a 77 cm capillary. Although most of the peaks arise from differences in the oligosaccharide structures present on the one glycosylation site on this molecule, other forms of micro-heterogeneity due to the presence of the nonglycosylated form of this glycoprotein and various types of chemical degradation, e.g., deamidation, are also responsible for the multitude of peaks observed. Although the exact chemical identity of each peak in the resulting electropherogram of this glycoprotein is not known, useful information can be obtained for assessing comparability, stability, and batch consistency. Factors impacting the resolution, precision, accuracy, and robustness of the assay are also discussed along with inherent advantages and limitations associated with measuring the micro-heterogeneity of intact glycoproteins.


Usefulness of late coronary thrombolysis (recombinant tissue-type plasminogen activator) in preserving left ventricular function in acute myocardial infarction.
This study assesses whether administration of recombinant tissue-type plasminogen activator (rt-PA) up to 8 hours after onset of symptoms of acute myocardial infarction (AMI) may result in a significant improvement in left ventricular function. Sixty patients were classified into 3 groups: group A (n = 21) received rt-PA within 4 hours from symptom onset; the remaining 39 patients, admitted between 4 and 8 hours, were randomized into 2 groups--group B (n = 19) received rt-PA, and group C (n = 21) was treated with conventional therapy. Coronary and left ventricular angiograms were recorded 8 to 10 days after rt-PA administration. The patency rate of the infarct-related artery was 76% in group A, and 63 and 35% in group B and C, respectively. The Thrombolysis in Myocardial Infarction trial perfusion grade was higher in group A and B than in group C (A vs C: p less than 0.005; B vs C: p less than 0.01). Left ventricular ejection fraction was significantly higher in group A (60.2 +/- 10%) and B (54.7 +/- 12%) compared with group C (44.2 +/- 12%) (A vs C: p less than 0.01; B vs C: p less than 0.05). Regional wall motion of the entire ischemic zone was better in group A and B than in group C (A vs C: p less than 0.001; B vs C: p less than 0.01). In contrast, the kinesis of the central ischemic zone was significantly better in group A than in both group B and C (A vs B: p less than 0.05; A vs C: p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of a Virtual Endoscopy Training Curriculum in Novice Endoscopists: First Experience in Argentina.
Virtual reality simulation in gastrointestinal endoscopy is an educational tool that allows repetitive instruction in a non-patient care environment. To determine the impact of a virtual endoscopy training curriculum applying an objective pre- and post-training analysis on trainee endoscopists. A before-after training study was carried out. Subjects were first year fellows of gastroenterology, who completed a questionnaire and then performed two pre-training simulated cases. The virtual endoscopy training curriculum consisted of an 8-h workday utilizing two GI MENTOR™ in a specialized clinical simulation center. After the training, all subjects completed the same two cases they did in the pre-training. Pre- and post-training results' comparisons were made by paired t test. Totally, 126 subjects were included (mean age 30 years, 61% female). A significant improvement from pre- to post-training was observed in psychomotor skills (total time, percentage, and number of balloons exploded) and endoscopic skills (cecal intubation time, percentage of examined mucosa, and efficacy of screening). There was also an improvement in the quality of the endoscopic study; percentage of examined mucosa over 85% showed a significant improvement post-training with an adjusted OR of 2.72 (95% CI 1.51-4.89, p = 0.001). Virtual endoscopy training curriculum produces a significant improvement in the trainee endoscopists performance and their psychomotor skills and introduces the concept of a quality endoscopic study in a non-patient, risk-free environment.


Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315).
An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the "real-world" setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany. This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1. In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4-10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9-9.2) with druggable ALK alterations. Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.


Development of a novel intelligent laparoscope system for semi-automatic minimally invasive surgery.
Intelligent surgical robot has great significance to alleviate the fatigue of surgeons. In the minimally invasive surgery robot system, adding intelligent control method to the laparoscope control has great realizability and significance. Depth independent image Jacobian matrix was modified to make it suitable for laparoscope trocar constraint. We propose a method for intelligent and autonomous adjustment of surgeon's surgical field of view, enabling it to track and predict the motion trajectory of surgical instruments. The result of experiment shows that the proposed method could realize tracking the surgical instruments and adjusting the surgical field of view autonomously. In case of occlusion, motion trajectory of surgical instruments can be predicted. The intelligent laparoscope system could improve the intelligent level of surgical robot system. Given providing "a third hand" for the surgeon, the proposed system is a highly improvement for semi-autonomous surgical robot system.


Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson's disease.
Aluminum and zinc have been related to the pathogenesis of Parkinson's disease (PD), the former for its neurotoxicity and the latter for its apparent antioxidant properties. 6-Hydroxydopamine (6-OHDA) is an important neurotoxin putatively involved in the pathogenesis of PD, its neurotoxicity often being related to oxidative stress. The potential effect of these metals on the oxidative stress induced by 6-OHDA autoxidation and the potential of ascorbic acid (AA), cysteine, and glutathione to modify this effect were investigated. Both metals, particularly Al3+, induced a significant reduction in *OH production by 6-OHDA autoxidation. The combined action of AA and a metal caused a significant and sustained increase in *OH generation, particularly with Al3+, while the effect of sulfhydryl reductants was limited to only the first few minutes of the reaction. However, both Al3+ and Zn2+ provoked a decrease in the lipid peroxidation induced by 6-OHDA autoxidation using mitochondrial preparations from rat brain, assessed by TBARS formation. In the presence of AA, only Al3+ induced a significant reduction in lipid peroxidation. After intrastriatal injections of 6-OHDA in rats, tyrosine hydroxylase immunohistochemistry revealed that Al3+ reduces 6-OHDA-induced dopaminergic lesion in the striatum, which corroborates the involvement of lipid peroxidation in 6-OHDA neurotoxicity and appears to discard the participation of this mechanism on PD by Al3+ accumulation. The previously reported antioxidant properties of Zn2+ appear to be related to the induction of Zn2+-containing proteins and not to the metal per se.


Does Automated Impaction Improve Femoral Component Sizing and Alignment in Total Hip Arthroplasty?
While automated impaction can provide a more standardized process for femoral canal preparation, little is known regarding its effect on femoral component sizing and position. The purpose of our study was to directly compare femoral component canal fill ratio (CFR) and coronal alignment between primary total hip arthroplasty (THA) procedures performed with automated impaction versus manual mallet impaction. A retrospective analysis was performed on 184 patients who underwent primary THA by a single arthroplasty surgeon between 2017 and 2021 with a modern cementless femoral component using either the direct anterior or posterolateral approach. The final cohort was divided into 2 groups based on impaction technique during broaching: automated (N = 122) or manual (N = 62). A propensity score match was used to match for age, body mass index, sex, high versus standard offset stem, and preoperative femoral bone quality. Radiographic review was performed to measure intramedullary prosthetic CFR and coronal alignment. The automated cohort trended toward the use of a larger stem (5.67 versus 4.82, P = .006) and had a larger CFR at all 4 levels within the proximal femur (P = .004). The automated cohort had a more valgus and reliable coronal alignment (-0.57 (SD 1.50) versus -0.03 (SD 2.17) degrees, P = .03) and significantly shorter operative time (mean 78 versus 90 minutes, P < .001). There were no intraoperative or postoperative periprosthetic fractures in either cohort. Automated impaction in primary THA is a safe technique for femoral preparation, which resulted in improved stem coronal alignment, optimized canal fill within the proximal femur, and reduced operative times.


Afferent and efferent connections of the mesencephalic reticular formation in goldfish.
The physiology of the mesencephalic reticular formation (MRF) in goldfish suggests its contribution to eye and body movements, but the afferent and efferent connections underlying such movements have not been determined. Therefore, we injected the bidirectional tracer biotinylated dextran amine into functionally identified MRF sites. We found retrogradely labelled neurons and anterogradely labelled boutons within nuclei of the following brain regions: (1) the telencephalon: a weak and reciprocal connectivity was confined to the central zone of area dorsalis and ventral nucleus of area ventralis; (2) the diencephalon: reciprocal connections were abundant in the ventral and dorsal thalamic nuclei; the central pretectal nucleus was also reciprocally wired with the MRF, but only boutons were present in the superficial pretectal nucleus; the preoptic and suprachiasmatic nuclei showed abundant neurons and boutons; the MRF was reciprocally connected with the preglomerular complex and the anterior tuberal nucleus; (3) the mesencephalon: neurons and boutons were abundant within deep tectal layers; reciprocal connections were also present within the torus semicircularis and the contralateral MRF; neurons were abundant within the nucleus isthmi; and (4) the rhombencephalon: the superior and middle parts of the reticular formation received strong projections from the MRF, while the projection to the inferior area was weaker; sparse neurons were present throughout the reticular formation; a reciprocal connectivity was observed with the sensory trigeminal nucleus; the medial and magnocellular nuclei of the octaval column projected to the MRF. These results support the participation of the MRF in the orienting response. The MRF could also be involved in other motor tasks triggered by visual, auditory, vestibular, or somatosensory signals.


Sublethal dietary effects of Microcystis on Sacramento splittail, Pogonichthys macrolepidotus.
The presence of the toxic cyanobacterium Microcystis in the upper San Francisco Estuary (SFE) since 1999 is a potential but to date an unquantified threat to the health and survival of aquatic organisms, such as fish and zooplankton. The microcystins (MCs) predominantly in the LR-form (MC-LR) contained in Microcystis is hepatotoxic and a potential threat to the fishery. This study was conducted to determine the effects of dietary exposure of the endemic Sacramento splittail, Pogonichthys macrolepidotus in SFE to Microcystis and its toxin, MC-LR. Juvenile splittail (12.59 ± 0.7 g fish(-1)) were exposed to five diets for 28 d with MC-LR obtained from: (1) Microcystis harvested from the SFE and (2) a synthetic purified form of MC-LR. Three of the test diets contained 3.55 (D5), 9.14 (D10) and 17.13 (D20)mg MC-LR kg(-1) from Microcystis. The other two diets contained either purified MC-LR at 3.89 mg MC-LR kg(-1) (D5R) or no MC-LR (D0). The RNA/DNA ratio of fish muscle was significantly lower for all treatments fed test diets containing MC-LR compared to the control diet D0, suggesting Microcystis adversely affected nutritional status. Protein phosphatase 2A expression in the fish from the D5, D10 and D20 treatments were inversely affected by increasing concentrations of MC-LR. Cytoplasmic inclusion bodies and single cell necrosis were more prevalent and greater in severity in the fish exposed to the diets D10 and D20 compared to fish from the D0 treatment and indicate severe liver toxicity in splittail exposed to MC-LR. The sublethal effects on splittail characterized by this study suggest cyanobacterial blooms have the potential to affect splittail nutritional status and health in SFE.


[Anatomical variations and anomalies of the musculus stapedius tendon. Study by scanning electron microscopy].
The authors used scanning electronic microscopy to investigate and define morphological characteristics of the musculus stapedius tendon: the opening through which the tendon protrudes at the eminentia pyramidalis and it can be found at its base. Fibers of the tendon may directly be attached to the bony surface of the stages or its prolongation of various forms and dimensions. In some cases the tendon fibrous bundles are more or less ossified. In one patient who was operate we found a congenital malformation manifested as absence of the tendon and deformation of the stapes. The tendon absence is found in 0.5% of cases.


Horseshoe kidney: retroperitoneoscopic nephrectomy.
The ideal approach for nephrectomy in the child with horseshoe kidney is debatable. We present two such children who underwent nephrectomy by a retroperitoneoscopic approach. Recognition of its anatomical variation is essential in the management of horseshoe kidney. Surgery is high risk, even using a traditional open procedure, because loss of the remaining half of the kidney is catastrophic.


Cutinase binding and activity at the triolein-water interface monitored by oil drop tensiometry.
Changes of the oil-water interfacial tension resulting from binding of Fusarium solani pisi cutinase and subsequent lipid hydrolysis were investigated using the oil drop technique. An ELISA was developed to determine the amount of cutinase bound to the triolein-water interface after biotinylation of the enzyme. Cutinase irreversibly adsorbs to a maximum value of about 2 mg/m2. A minimal specific activity of 110 mumol/min/mg was calculated for cutinase acting on a single oil droplet, which is close to the activity found for triglyceride emulsions. At a maximum surface load cutinase could generate one monolayer of fatty acid products per second at the interface. It was found that oleic acid rapidly dissolves into the oil phase under the conditions used. The interfacial tension measured reflects the adsorption of cutinase to the oil droplet and also responds to the fate of the hydrolysis products. A model is presented that describes the catalytic events at the oil-water interface during lipid hydrolysis.


Insensitive ionic bio-energetic materials derived from amino acids.
Energetic salts/ionic liquids have received increasing attention as fascinating energetic materials, and the use of renewable compounds is a promising approach to developing energetic materials. Until recently, biomolecules have been used as raw materials to develop neutral energetic compounds, whereas research focused on ionic energetic materials obtained from natural bio-renewable frameworks is scarce. This work systematically investigates ionic bio-energetic materials (IBEMs) derived from sustainable natural amino acids. In addition to combustibility, high density, good thermal stability, and one-step preparation, these IBEMs demonstrated apparent hypotoxicity and insensitivity. Moreover, a theoretical examination was performed to explore their appropriate properties. The intriguing results of this study indicates that IBEMs are potential bio-based energetic materials.


Computerised provider order entry combined with clinical decision support systems to improve medication safety: a narrative review.
Adverse drug events (ADEs) are a major cause of morbidity in hospitalised and ambulatory patients. Computerised provider order entry (CPOE) combined with clinical decision support systems (CDSS) are being widely implemented with the goal of preventing ADEs, but the effectiveness of these systems remains unclear. We searched the specialised database Agency for Healthcare Research and Quality (AHRQ) Patient Safety Net to identify reviews of the effect of CPOE combined with CDSS on ADE rates in inpatient and outpatient settings. We included systematic and narrative reviews published since 2008 and controlled clinical trials published since 2012. We included five systematic reviews, one narrative review and two controlled trials. The existing literature consists mostly of studies of homegrown systems conducted in the inpatient setting. CPOE+CDSS was consistently reported to reduce prescribing errors, but does not appear to prevent clinical ADEs in either the inpatient or outpatient setting. Implementation of CPOE+CDSS profoundly changes staff workflow, and often leads to unintended consequences and new safety issues (such as alert fatigue) which limit the system's safety effects. CPOE+CDSS does not appear to reliably prevent clinical ADEs. Despite more widespread implementation over the past decade, it remains a work in progress.


Perceptions of stroke recovery: an exclusion of communication and cognition.
Perceptions of stroke recovery can differ substantially between stroke survivors and their healthcare providers. Concordance between the two is important for collaborative goal setting to facilitate optimal outcomes. To explore stroke survivors' perceptions of their own recovery and residual impairments with specific emphasis on communication and cognition. A qualitative analytic approach was used in the study. Nine stroke survivors participated in a focus group discussion as part of a larger study designed to examine post-stroke outcomes. Early in the focus group proceedings, a discussion emphasizing how stroke survivors perceive their overall recovery emerged. Six of the nine participants (67%) perceived their overall stroke recovery to be greater than 90%, and only physical impairments were reported. Later in the course of the interview, eight of the nine participants (89%) reported either word retrieval or memory loss deficits which negatively influenced their daily functional activities. Stroke survivors in this sample did not include communication and cognitive deficits in their perception of their overall recovery despite later reporting these symptoms and related impairment. Failure of patients to include such persisting deficits in their reports of recovery can cause a mismatch between stroke survivor and provider goals.


Identifying and preventing degradation in flavin mononucleotide-based redox flow batteries via NMR and EPR spectroscopy.
While aqueous organic redox flow batteries (RFBs) represent potential solutions to large-scale grid storage, their electrolytes suffer from short lifetimes due to rapid degradation. We show how an understanding of these degradation processes can be used to dramatically improve performance, as illustrated here via a detailed study of the redox-active biomolecule, flavin mononucleotide (FMN), a molecule readily derived from vitamin B2. Via in-situ nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) we identify FMN hydrolysis products and show that these give rise to the additional plateau seen during charging of an FMN-cyanoferrate battery. The redox reactions of the hydrolysis product are not reversible, but we demonstrate that capacity is still retained even after substantial hydrolysis, albeit with reduced voltaic efficiency, FMN acting as a redox mediator. Critically, we demonstrate that degradation is mitigated and battery efficiency is substantially improved by lowering the pH to 11. Furthermore, the addition of cheap electrolyte salts to tune the pH results in a dramatic increase in solubility (above 1 M), this systematic improvement of the flavin-based system bringing RFBs one step closer to commercial viability.


SABCS 2017: update on chemotherapy, targeted therapy, and immunotherapy.
In the areas of chemotherapy, targeted therapy and immunotherapy, several interesting and clinically relevant data were presented at the 2017 San Antonio Breast Cancer Symposium (SABCS). This short review focuses on dose-dense and/or sequential administration of adjuvant chemotherapy, provides an update on targeted therapies for HER2-positive and triple-negative breast cancer and summarizes new results in the field of immunotherapy.


Love is analogous to money in human brain: Coordinate-based and functional connectivity meta-analyses of social and monetary reward anticipation.
Both social and material rewards play a crucial role in daily life and function as strong incentives for various goal-directed behaviors. However, it remains unclear whether the incentive effects of social and material reward are supported by common or distinct neural circuits. Here, we have addressed this issue by quantitatively synthesizing and comparing neural signatures underlying social (21 contrasts, 207 foci, 696 subjects) and monetary (94 contrasts, 1083 foci, 2060 subjects) reward anticipation. We demonstrated that social and monetary reward anticipation engaged a common neural circuit consisting of the ventral tegmental area, ventral striatum, anterior insula, and supplementary motor area, which are intensively connected during both task and resting states. Functional decoding findings indicate that this generic neural pathway mediates positive value, motivational relevance, and action preparation during reward anticipation, which together motivate individuals to prepare well for the response to the upcoming target. Our findings support the common neural currency hypothesis by providing the first meta-analytic evidence to quantitatively show the common involvement of brain regions in both social and material reward anticipation.


Revolution of vitamin E production by starting from microbial fermented farnesene to isophytol.
Vitamin E is one of the most widely used vitamins. In the classical commercial synthesis of vitamin E (α-tocopherol), the chemical synthesis of isophytol is the key technical barrier. Here, we establish a new process for isophytol synthesis from microbial fermented farnesene. To achieve an efficient pathway for farnesene production, Saccharomyces cerevisiae was selected as the host strain. First, β-farnesene synthase genes from different sources were screened, and through protein engineering and system metabolic engineering, a high production of β-farnesene in S. cerevisiae was achieved (55.4 g/L). This farnesene can be chemically converted into isophytol in three steps with approximately 92% yield, which is economically equal to that from the best total chemical synthesis. Furthermore, we co-produced lycopene and farnesene to reduce the cost of farnesene. A factory based on this new process was successfully operated in Hubei Province, China, in 2017, with an annual output of 30,000 tons of vitamin E. This new process has completely changed the vitamin E market due to its low cost and safety.


Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection.
Most commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety. To address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection. We demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan. β-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host's innate and adaptive immunity. Our study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine's safety and efficacy, it represents a breakthrough among next-generation FMD vaccines.


Clinical predictors of subtherapeutic aminoglycoside levels in trauma patients undergoing once-daily dosing.
After publication of the Hartford nomogram in 1995, conflicting data have emerged regarding the use of once-daily aminoglycoside (ODA) regimens in critically ill patients. The purpose of this study was to characterize a trauma patient population with low 10-hour aminoglycoside levels (THL) within the Hartford ODA protocol. Patients admitted to a Level I trauma center who received aminoglycosides were eligible for study. Clinical and demographic data were prospectively collected. Patients were dosed according to the Hartford protocol and a THL was obtained. Patients with THL < 2.0 microg/mL (OFF cohort) were compared with those falling within the nomogram (ON cohort). Of 79 patients receiving ODA therapy, 46 (58.2%) patients fell off the nomogram. The OFF cohort was associated with younger age and higher creatinine clearance, and related inversely to net resuscitative volume. Trauma patients undergoing ODA therapy with low THL are younger and exhibit less net preaminoglycoside resuscitative volume and higher creatinine clearance. These findings may have important clinical implications regarding antibiotic efficacy in these select patients.


Antiasthmatic effects of onions. Inhibition of platelet-activating factor-induced bronchial obstruction by onion oils.
Lyophilized onion extract and ether extracts of onions were separated by chromatographic methods into several subfractions and tested for their effects on asthmatic reactions of guinea pigs to allergen, histamine, acetylcholine and platelet-activating factor (PAF) inhalation as well as on thromboxane biosynthesis of human platelets and lung fibroblasts. Onion oils are counteracting the bronchial obstruction due to PAF inhalation.


A review of the potential neurological adverse events of COVID-19 vaccines.
Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain-Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell's palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.


Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.
Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed.


Current Status and Trends in Research on Caries Diagnosis: A Bibliometric Analysis.
There are a wide variety of devices for the detection and diagnosis of caries from the initial stages. The purpose of this study was to perform a bibliometric study on research regarding caries diagnosis by identifying the contributing researchers, organizations, countries or regions, journals, and to provide an analysis of keyword co-occurrence and co-authorship networks. An advanced search was performed in Web of Science (WOS) Core Collection database, using the terms "caries diagno*" and "caries detect*" in the "topic" field, from 2013 to 2021. Bibliometric parameters were extracted using WOS's analyze results tools and VOSviewer software. A total of 816 documents were identified. Most of them, (61.3%) are included in "Dentistry Oral Surgery & Medicine" category within WOS. The largest scientific production on the subject is observed between 2018 and 2021, with a total of 344 records. The most productive author is Mendes FM, followed by Braga MM. The journal with the most articles published on caries diagnosis is Caries Research, with 55 articles (6.74%). The terms with the highest co-occurrence refer to the validity of diagnostic methods, tools or principles used in diagnosis or general aspects related to caries detection and diagnosis.


Soft drugs. 19. Pharmacokinetics, metabolism and excretion of a novel soft corticosteroid, loteprednol etabonate, in rats.
Pharmacokinetics, metabolism and excretion of loteprednol etabonate (LE) were investigated in rats. The pharmacokinetic studies were performed by iv injections of LE (1-20 mg/kg). In the metabolism and excretion studies, 0.5-10 mg/kg of LE were iv administered, bile and urine samples were collected for 6 hr. The pharmacokinetic of LE showed a rapid, dose-dependent elimination with a total blood clearance (CLtotal) of higher than 60 ml/min/kg. The metabolism and excretion of LE also showed a marked dose-dependency. At 6 hr after iv of LE (0.5-10 mg/kg), the total recoveries (LE and the metabolites, AE & A, in bile and urine) were 99.35-26.72%. However, only about 2% of LE was excreted from the body through the urine. There were 0.93-2.12% and 0.66-0.26% of AE, and 75.67-19.69% and 20.74-2.77% of A excreted in the bile and urine, respectively. The excretion of A was dose dependent, and significantly higher at the lower dose. Using the (% of total excretion) vs. (log dose) plots, it could be predicted that almost all of the administered LE will be metabolized, and excreted as A when the systemic dose is lower than 0.25 mg/kg. The results indicate that LE absorbed systemically, after topical administration, can be rapidly transformed to the inactive metabolites, and eliminated from the body mainly through the bile and urine.


A study of HER-2/neu expression and silver binding nucleolar organizer regions (Ag NORs) in perilesional normal salivary gland tissue.
Salivary gland neoplasms comprise phenotypically and biologically diverse lesions of uncertain histogenesis. The present study was carried out to assess the immunohistochemical expression of HER-2/neu protein and of silver binding nucleolar organizer regions in normal salivary tissue. Twenty paraffin blocks of salivary tumors containing surrounding normal salivary tissue were used in the study. One section was processed to investigate HER-2/neu protein expression and another section was stained to assess the mean Ag NOR counts in normal salivary tissue. Only two cases of the studied normal salivary tissue showed HER-2/neu expression (10%), which was expressed only in ductal cells with 4.2 ± 2.1 mean number of reactive cells per five high power fields (HPFs). Statistically significant (P = 0.01) higher mean Ag NOR counts in ductal (2 ± 0.83) than in acinar cells (1.2 ± 0.01) of normal salivary tissue were found. It was concluded from the data of the present study that ductal cells of normal salivary tissue are a proliferative pool and an oncogenic target which plays an important role in the histogenesis of salivary gland tumors.