Identification and visualisation of microplastics/nanoplastics by Raman imaging (i): Down to 100 nm.
While microplastics (1 μm-5 mm) contamination is creating public concern, nanoplastics (<1000 nm) might create even more serious environmental contamination issues. This is likely due to the smaller size/higher specific surface area of nanoplastics which works more efficiently as a vector for other contaminants' transportation and fate, to release the formulation additives and to be accumulated in the human body. The research on nanoplastics is currently hampered by the absence of an effective characterisation method, although X-ray photoelectron spectroscopy/Scanning Electron Microscopy (XPS/SEM) is reportedly dominating the nanoplastics characterisation approaches. Recently, imaging technology, which provides direct visualisation of the targets, is attracting increased attention. In this study, we demonstrate that Raman imaging can be employed to visualise and identify microplastics and nanoplastics down to 100 nm, by distinguishing the laser spot, the pixel size/image resolution, the nanoplastics size/position (within a laser spot), the Raman signal intensity, and via the sample preparation etc. We also validate this technique for the analysis of paint-polishing dust samples that have been collected from a driveway when a vehicle's clear coating of poly-acrylic was polished by hand. We estimate that billions-trillions of microplastics/nanoplastics ranging from ∼7 μm down to ∼200 nm have been generated by hand-polishing an engine hood.


Neighborhoods at risk: estimating risk of higher Neisseria gonorrhoeae incidence among women at the census tract level.
The association between area-based social factors and sexually transmitted diseases has been demonstrated in numerous studies. Such associations have not previously been explored for their potential to quantify likelihood of higher transmission of gonorrhea in small geographic areas. Aggregate census tract-level sociodemographic factors in 4 domains (demographics, educational attainment, household income, and housing characteristics) were merged with female gonorrhea incidence data from 113 counties in 10 US states. Multivariate models were constructed, and a tract-level composite gonorrhea risk index was calculated. This composite risk index was validated against gonorrhea incidence among women from 2 independent states. Seven tract-level factors were found to be most strongly correlated with female gonorrhea incidence: educational attainment, proportion of female headed households, annual household income below US $20,000, proportion of population non-Hispanic black, proportion of housing units currently vacant, proportion of population reporting moving in last year, and proportion of households that are nonfamily units. Composite index was highly correlated with female gonorrhea in the study area and validated with independent data. Social factors predict gonorrhea incidence at the census tract level and identify small areas at risk for higher morbidity. These data may be used by health departments and health care practices to develop geographically based disease prevention and control efforts. This is especially useful because gonorrhea incidence data are not routinely available below the county level in many states.


Risk factors for 30-day readmission in adults hospitalized for pulmonary hypertension.
Readmissions for pulmonary hypertension are poorly understood and understudied. We sought to determine national estimates and risk factors for 30-day readmission after pulmonary hypertension-related hospitalizations. We utilized the Healthcare Cost and Utilization Project Nationwide Readmission Database, which has weighted estimates of roughly 35 million discharges in the US. Adult patients with primary International Classification of Disease, Ninth Revision, Clinical Modification diagnosis codes of 416.0 and 416.8 for primary and secondary pulmonary hypertension with an index admission between 2012 and 2014 and any readmission within 30 days of the index event were identified. Predictors of 30-day readmission were identified using multivariable logistic regression with adjustment for covariates. Results showed that the national estimate for Primary Pulmonary Hypertension vs Secondary Pulmonary Hypertension-related index events between 2012 and 2014 with 30-day readmission was 247 vs 2550 corresponding to a national readmission risk estimate of 17% vs 18.3%, respectively. The presence of fluid and electrolyte disorders, renal failure, and alcohol abuse were associated with increased risk of readmission in Primary Pulmonary Hypertension, while factors associated with Secondary Pulmonary Hypertension readmissions included anemia, congestive heart failure, lung disease, fluid and electrolyte disorders, renal failure, diabetes, and liver disease. The median cost of Primary Pulmonary Hypertension admissions and readmissions were $46,132 (IQR: $25,384-$85,647) and $41,604.50 (IQR: $22,481.50-$84,420.50), respectively. The median costs of Secondary Pulmonary Hypertension admissions and readmissions were $34,893 (IQR: $19,670-$66,143) and $36,279 (IQR: $19,059-$74,679), respectively. In conclusion, approximately 19% of Primary Pulmonary Hypertension and Secondary Pulmonary Hypertension hospitalizations result in 30-day readmission, with significant costs accrued during the index hospitalization and readmission. With evolving clinical terminology and diagnostic codes, future study will need to better clarify underlying factors associated with readmissions amongst pulmonary hypertension sub-types, and identify methods and procedures to minimize readmission risk.


A DVH-guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning.
To develop a novel algorithm that incorporates prior treatment knowledge into intensity modulated radiation therapy optimization to facilitate automatic treatment planning and adaptive radiotherapy (ART) replanning. The algorithm automatically creates a treatment plan guided by the DVH curves of a reference plan that contains information on the clinician-approved dose-volume trade-offs among different targets/organs and among different portions of a DVH curve for an organ. In ART, the reference plan is the initial plan for the same patient, while for automatic treatment planning the reference plan is selected from a library of clinically approved and delivered plans of previously treated patients with similar medical conditions and geometry. The proposed algorithm employs a voxel-based optimization model and navigates the large voxel-based Pareto surface. The voxel weights are iteratively adjusted to approach a plan that is similar to the reference plan in terms of the DVHs. If the reference plan is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan with the DVHs better than the reference ones. If the reference plan is too restricting for the new geometry, the algorithm generates a Pareto plan with DVHs close to the reference ones. In both cases, the new plans have similar DVH trade-offs as the reference plans. The algorithm was tested using three patient cases and found to be able to automatically adjust the voxel-weighting factors in order to generate a Pareto plan with similar DVH trade-offs as the reference plan. The algorithm has also been implemented on a GPU for high efficiency. A novel prior-knowledge-based optimization algorithm has been developed that automatically adjust the voxel weights and generate a clinical optimal plan at high efficiency. It is found that the new algorithm can significantly improve the plan quality and planning efficiency in ART replanning and automatic treatment planning.


A case of haemolytic disease of the fetus and newborn attributed to a novel antigen in the RHAG blood group system.
A newborn presented with jaundice in Thailand. The cord red cells tested positive by direct antiglobulin test (DAT) for an unknown maternal red cell antibody. Initial blood group sequencing suggested that the infant carried a novel variant RHAG c.140T>C, responsible for a low-prevalence antigen in the RHAG blood group system (ISBT 030). We report here on testing of samples from the infant's parents and older sibling to define a new antigen in the RHAG system. Massive parallel sequencing (MPS) using a custom-designed panel was performed on all four family members. Extended serological testing was also performed to determine whether family members with the same variant as the infant showed reactivity with the antibody in the maternal plasma. We identified a novel single nucleotide variant (SNV) (RHAG c.140T>C, p.[Phe47Ser]) in samples from three of the four family members tested (the infant, the older sibling and the father). The variant was not detected in the mother's sample. Maternal plasma showed positive agglutination with all family members tested; however, when tested with routine panel cells, no reactivity was observed. This case study showed that the presence of the novel variant (RHAG c.140T>C), encoding a p.(Phe47Ser) change in the RhAG glycoprotein, was the apparent cause of incompatibility between maternal plasma and that of red cells from the proband, father and older sibling of the proband. We propose this variant to be a new low-prevalence antigen in the RHAG blood group system.


cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2.
The epithelial Na(+) channel (ENaC) functions as a pathway for epithelial Na(+) transport, contributing to Na(+) homeostasis and blood pressure control. Vasopressin increases ENaC expression at the cell surface through a pathway that includes cAMP and cAMP-dependent protein kinase (PKA), but the mechanisms that link PKA to ENaC are unknown. Here we found that cAMP regulates Na(+) transport in part by inhibiting the function of Nedd4-2, an E3 ubiquitin-protein ligase that targets ENaC for degradation. Consistent with this model, we found that cAMP inhibited Nedd4-2 by decreasing its binding to ENaC. Moreover, decreased Nedd4-2 expression (RNA interference) or overexpression of a dominant negative Nedd4-2 construct disrupted ENaC regulation by cAMP. Nedd4-2 was a substrate for phosphorylation by PKA in vitro and in cells; three Nedd4-2 residues were phosphorylated by PKA and were required for cAMP to inhibit Nedd4-2 (relative functional importance Ser-327 > Ser-221 > Thr-246). Previous work found that these residues are also phosphorylated by serum and glucocorticoid-inducible kinase (SGK), a downstream mediator by which aldosterone regulates epithelial Na(+) transport. Consistent with a functional interaction between these pathways, overexpression of SGK blunted ENaC stimulation by cAMP, whereas inhibition of SGK increased stimulation. Conversely, cAMP agonists decreased ENaC stimulation by SGK. The data suggest that cAMP regulates ENaC in part by phosphorylation and inhibition of Nedd4-2. Moreover, Nedd4-2 is a central convergence point for kinase regulation of Na(+) transport.


The Cattle Fever Tick, Rhipicephalus microplus, as a Model for Forward Pharmacology to Elucidate Kinin GPCR Function in the Acari.
The success of the acaricide amitraz, a ligand of the tick tyramine/octopamine receptor (a G protein-coupled receptor; GPCR), stimulated interest on arthropod-specific GPCRs as targets to control tick populations. This search advances tick physiology because little is known about the pharmacology of tick GPCRs, their endogenous ligands or their physiological functions. Here we explored the tick kinin receptor, a neuropeptide GPCR, and its ligands. Kinins are pleiotropic insect neuropeptides but their function in ticks is unknown. The endogenous tick kinins are unknown and their cDNAs have not been cloned in any species. In contrast, more than 271 insect kinin sequences are available in the DINeR database. To fill this gap, we cloned the kinin cDNA from the cattle fever tick, Rhipicephalus microplus, which encodes 17 predicted kinins, and verified the kinin gene structure. We predicted the kinin precursor sequences from additional seven tick species, including Ixodes scapularis. All species showed an expansion of kinin paracopies. The "kinin core" (minimal active sequence) of tick kinins FX1X2WGamide is similar to those in insects. Pro was predominant at the X2 position in tick kinins. Toward accelerating the discovery of kinin function in ticks we searched for novel synthetic receptor ligands. We developed a dual-addition assay for functional screens of small molecules and/or peptidomimetics that uses a fluorescent calcium reporter. A commercial library of fourteen small molecules antagonists of mammalian neurokinin (NK) receptors was screened using this endpoint assay. One acted as full antagonist (TKSM02) with inhibitory concentration fifty (IC50) of ∼45 μM, and three were partial antagonists. A subsequent calcium bioluminescence assay tested these four antagonists through kinetic curves and confirmed TKSM02 as full antagonist and one as partial antagonist (TKSM14). Antagonists of NK receptors displayed selectivity (>10,000-fold) on the tick kinin receptor. Three peptidomimetic ligands of the mammalian NK receptors (hemokinin 1, antagonist G, and spantide I) were tested in the bioluminescence assay but none were active. Forward approaches may accelerate discovery of kinin ligands, either as reagents for tick physiological research or as lead molecules for acaricide development, and they demonstrate that selectivity is achievable between mammalian and tick neuropeptide systems.


A randomised controlled trial evaluating family mediated exercise (FAME) therapy following stroke.
Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke. A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s) assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study. This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice. The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744).


Identifying optimal models to represent biochemical systems.
Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.


Replacing saturated fat with PUFA-rich (sunflower oil) or MUFA-rich (rapeseed, olive and high-oleic sunflower oil) fats resulted in comparable hypocholesterolemic effects in cholesterol-fed hamsters.
Recent studies have suggested that monounsaturated fatty acid (MUFA)-rich dietary fats do not have the same plasma cholesterol-lowering effects whereby rapeseed oil was more effective than olive oil. This phenomenon could be explicable by the content of other fatty acids or plant sterols. To further evaluate the effects of different MUFA-rich oils (18:1-rich sunflower oil, rapeseed oil, olive oil) in comparison to polyunsaturated (PUFA)-rich oils (18:2-rich sunflower oil) and saturated fat (palm stearin) on cholesterol and bile acid metabolism, male Syrian golden hamsters were fed semipurified diets containing 5% fat and 0.2% cholesterol for 5 weeks. To test whether oil refining would have an impact on the cholesterol-lowering potential, unrefined and refined varieties of rapeseed and olive oil were included. After 5 weeks, plasma total cholesterol (TC) was highest with palm stearin (10.0 +/- 2.6 mmol/l) while the MUFA- or PUFA-rich fats significantly lowered TC. The lowest TC concentrations were found with refined rapeseed, cold pressed rapeseed and 18:2-rich sunflower oil (6.7 +/- 1.2; 7.1 +/- 0.7 and 7.1 +/- 0.7 mmol/l, respectively), whereas TC was 10-15% higher (not significant) with 18:1-rich sunflower, virgin and refined olive oil. Liver cholesterol concentrations were lowest in hamsters fed palm stearin or 18:2-rich sunflower oil while MUFA-rich fats increased hepatic cholesteryl ester accumulation, especially of cholesteryl oleate. There were no significant differences in the fecal neutral sterol and bile acid excretion. These data demonstrate that MUFA-rich dietary fats, e.g. rapeseed, olive and 18:1-rich sunflower oil, are comparable in their hypocholesterolemic potential and cause similar effects on plasma cholesterol as 18:2-rich sunflower oil in hamsters when the dietary cholesterol intake is moderate.


Improvement in mortality rates in bleeding peptic ulcer disease: Royal North Shore Hospital of Sydney, 1947-1977.
A series of patients with upper gastrointestinal haemorrhage treated at the Royal North Shore Hospital from 1976 to 1977 was compared to a similar series treated from 1947 to 1949. Although over-all mortality rates were similar, a clear improvement emerged when variceal, carcinoma and stress ulcer patients were excluded, and when the effect of age was taken into account (the mortality rate in the non-variceal, non-cancer, non-stress patients being 2% over-all, and 1.5% in those under 60 years of age). A review of the English literature on upper gastrointestinal haemorrhage from 1930 to 1977 showed no improvement in over-all mortality over this period. When these same factors were taken into account, however, the survival in the non-stress, chronic peptic ulcer group aged over 60 years was found to have significantly improved over this time.


Electromagnetic degrees of freedom of an optical system
We present a rigorous electromagnetic formalism for defining, evaluating, and optimizing the degrees of freedom of an optical system. The analysis is valid for the delivery of information with electromagnetic waves under arbitrary boundary conditions communicating between domains in three-dimensional space. We show that, although in principle there is an infinity of degrees of freedom, the effective number is finite owing to the presence of noise. This is in agreement with the restricted classical theories that showed this property for specific optical systems and within the scalar and paraxial approximations. We further show that the best transmitting and receiving functions are the solutions of well-defined eigenvalue equations. The present approach is useful for understanding and designing modern optical systems for which the previous approaches are not applicable, as well as for application in inverse and synthesis problems.


Dissecting the regions of virion-associated Kaposi's sarcoma-associated herpesvirus complement control protein required for complement regulation and cell binding.
Complement, which bridges innate and adaptive immune responses as well as humoral and cell-mediated immunity, is antiviral. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a lytic cycle protein called KSHV complement control protein (KCP) that inhibits activation of the complement cascade. It does so by regulating C3 convertases, accelerating their decay, and acting as a cofactor for factor I degradation of C4b and C3b, two components of the C3 and C5 convertases. These complement regulatory activities require the short consensus repeat (SCR) motifs, of which KCP has four (SCRs 1 to 4). We found that in addition to KCP being expressed on the surfaces of experimentally infected endothelial cells, it is associated with the envelope of purified KSHV virions, potentially protecting them from complement-mediated immunity. Furthermore, recombinant KCP binds heparin, an analogue of the known KSHV cell attachment receptor heparan sulfate, facilitating infection. Treating virus with an anti-KCP monoclonal antibody (MAb), BSF8, inhibited KSHV infection of cells by 35%. Epitope mapping of MAb BSF8 revealed that it binds within SCR domains 1 and 2, also the region of the protein involved in heparin binding. This MAb strongly inhibited classical C3 convertase decay acceleration by KCP and cofactor activity for C4b cleavage but not C3b cleavage. Our data suggest similar topological requirements for cell binding by KSHV, heparin binding, and regulation of C4b-containing C3 convertases but not for factor I-mediated cleavage of C3b. Importantly, they suggest KCP confers at least two functions on the virion: cell binding with concomitant infection and immune evasion.


Soft Radio-Frequency Identification Sensors: Wireless Long-Range Strain Sensors Using Radio-Frequency Identification.
Increasing amounts of attention are being paid to the study of Soft Sensors and Soft Systems. Soft Robotic Systems require input from advances in the field of Soft Sensors. Soft sensors can help a soft robot to perceive and to act upon its immediate environment. The concept of integrating sensing capabilities into soft robotic systems is becoming increasingly important. One challenge is that most of the existing soft sensors have a requirement to be hardwired to power supplies or external data processing equipment. This requirement hinders the ability of a system designer to integrate soft sensors into soft robotic systems. In this article, we design, fabricate, and characterize a new soft sensor, which benefits from a combination of radio-frequency identification (RFID) tag design and microfluidic sensor fabrication technologies. We designed this sensor using the working principle of an RFID transporter antenna, but one whose resonant frequency changes in response to an applied strain. This new microfluidic sensor is intrinsically stretchable and can be reversibly strained. This sensor is a passive and wireless device, and as such, it does not require a power supply and is capable of transporting data without a wired connection. This strain sensor is best understood as an RFID tag antenna; it shows a resonant frequency change from approximately 860 to 800 MHz upon an applied strain change from 0% to 50%. Within the operating frequency, the sensor shows a standoff reading range of >7.5 m (at the resonant frequency). We characterize, experimentally, the electrical performance and the reliability of the fabrication process. We demonstrate a pneumatic soft robot that has four microfluidic sensors embedded in four of its legs, and we describe the implementation circuit to show that we can obtain movement information from the soft robot using our wireless soft sensors.


Spin dynamics of [1,2-13C2]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields.
Hyperpolarization of 13C-pyruvate via Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for in vitro or in vivo studies. Here, we analyze the [1,2-13C2]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride-13C2 Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride-13C2-CH3 system. The analytical and the numerical results are compared to matching systematic experiments. With these methods we unravel the observed spin state mixing of singlet states and triplet states at microTesla fields and we also analyze the dynamics during transfer from micro-Tesla field to high field for detection to understand the resulting spectra from the [1,2-13C2]pyruvate-SABRE system.


ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study.
The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively. Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P<0.0001), indicating improvement in health-related quality of life. ExtaviJect 30G was convenient to use and was associated with high levels of compliance.


Allosteric inhibitors of plasma membrane Ca pumps: Invention and applications of caloxins.
Plasma membrane Ca(2+) pumps (PMCA) play a major role in Ca(2+) homeostasis and signaling by extruding cellular Ca(2+) with high affinity. PMCA isoforms are encoded by four genes which are expressed differentially in various cell types in normal and disease states. Therefore, PMCA isoform selective inhibitors would aid in delineating their role in physiology and pathophysiology. We are testing the hypothesis that extracellular domains of PMCA can be used as allosteric targets to obtain a novel class of PMCA-specific inhibitors termed caloxins. This review presents the concepts behind the invention of caloxins and our progress in this area. A section is also devoted to the applications of caloxins in literature. We anticipate that isoform-selective caloxins will aid in understanding PMCA physiology in health and disease. With strategies to develop therapeutics from bioactive peptides, caloxins may become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer and contraception.


Effects of two field continuous incremental tests on cardiorespiratory responses in Standardbred trotters.
In humans, cardiorespiratory responses are widely evaluated from field incremental exercise tests. On the contrary, equine exercise physiology faces a huge lack of oxygen consumption measurements (VO2) in field conditions due to technical concerns. The aim of this study was to test the effects of two incremental continuous field tests on cardiorespiratory responses in Standardbred trotters. The two protocols were realized at trot and ended when horses galloped. The tests started at 4.2 m/s (T1) and 6.4 m/s (T2), with speed increments of 1.4 m/s every 3 min for T1 and 0.8 m/s every 2 min for T2. Velocity (v), heart rate (HR) and gas exchanges were recorded continuously, and blood lactate concentration [La(-)] was measured before and after tests. Values recorded at the end of the tests were considered as peak values. The vpeak values were 10.6 ± 0.3 and 10.7 ± 0.7 m/s for T1 and T2 respectively. Horses reached higher VO2peak (T1: 116.6 ± 11.5 ml/min/kg; T2: 88.9 ± 10.2 ml/min/kg; p < 0.05) and HRpeak (T1: 217 ± 5 bpm; T2: 209 ± 3 bpm; p < 0.05) during T1 compared with T2. T1 was significantly longer than T2 (17.5 ± 1.9 vs. 12.9 ± 1.6 min respectively, p < 0.01), and the number of steps entirely ran tended to be different (T1: 5.6 ± 0.6; T2: 6.2 ± 0.8, p = 0.07). Compared to T2, the design of T1 appeared easier to implement and allowed higher cardiorespiratory responses. The relationship between HR-VO2 obtained through T1 gave a better correlation between the two variables than T2. These findings suggest that T1 might be better than T2 for evaluating cardiorespiratory adaptations to exercise and for estimating aerobic energy expenditure in exercising trotters.


Effects of Calcium Plus Vitamin D Supplementation on Anthropometric Measurements and Blood Pressure in Vitamin D Insufficient People with Type 2 Diabetes: A Randomized Controlled Clinical Trial.
Up to 75% of the risk of type 2 diabetes is attributable to obesity. Therefore, finding a way to control obesity can be useful for management of diabetes. This study was performed to assess the effects of vitamin D3 and calcium supplementation on anthropometric measurements and blood pressure in vitamin D insufficient people with type 2 diabetes. One hundred eighteen patients with diabetes were enrolled in this randomized placebo-controlled clinical trial. All subjects were randomly assigned into 4 groups receiving (1) 50,000 IU/wk vitamin D3 plus (equal to 7143 IU/d) calcium placebo; (2) 1000 mg/d calcium plus vitamin D3 placebo; (3) 50,000 IU/wk vitamin D3 (equal to 7143 IU/d) plus 1000 mg/d calcium; or (4) vitamin D3 placebo plus calcium placebo for 8 weeks. Anthropometric measurements and blood pressure were assessed at study baseline and after 8 weeks of intervention. A greater reduction in body mass index was observed in calcium plus vitamin D group than other groups (p = 0.03). Comparison of changes in waist circumference among 4 groups revealed no significant difference in crude model (p = 0.21) and when the effect of confounders was taken into account (p = 0.08). Calcium supplementation resulted in a significant reduction in hip circumference compared to other groups (p <0.001). Systolic blood pressure significantly decreased in the calcium plus vitamin D group compared to placebo (-7.3 ± 8.7 mmHg vs 0.5 ± 8.2 mmHg; p = 0.001). However, calcium and vitamin D supplementation had no significant effects on diastolic blood pressure. Calcium-vitamin D3 cosupplementation can have beneficial effect on body mass index (BMI), hip circumference, and systolic blood pressure in vitamin D-insufficient type 2 diabetics.


Phylogeny Predicts the Quantity of Antimalarial Alkaloids within the Iconic Yellow Cinchona Bark (Rubiaceae: Cinchona calisaya).
Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood.


Interlayer cross talk in dual-layer read-only optical disks.
Volumetric optical disks comprising multiple data layers have been proposed to multiply recording density. Owing to the presence of out-of-focus data layers, interlayer cross talk is induced in readout. An optical model was developed to study the readout process and the effect of interlayer cross talk on the readout of dual-layer read-only optical disks. Schemes to improve the readout characteristics by suppression of the interlayer cross talk were proposed. Experiments that agreed well with the simulation resulted.


Attention deficit hyperactivity disorder (ADHD) symptoms, comorbid psychopathology, behaviour problems and gastrointestinal symptoms in children and adolescents with autism spectrum disorder.
The study aims to investigate attention deficit hyperactivity disorder (ADHD) symptoms, gastrointestinal (GI) symptoms, comorbid psychopathology and behaviour problems in children and adolescents with autism spectrum disorder (ASD). Parents of 147 children and adolescents with ASD aged 6-18 years completed the Conners 3 Parent-Short Form, Gastrointestinal Symptom Inventory, Behavior Problems Inventory-Short Form and Autism Spectrum Disorder-Comorbid for Children. Fifty-six per cent of children and adolescents had a comorbid diagnosis of ADHD, yet over 70% presented with clinically significant ADHD symptoms. Forty per cent of participants received a diagnosis of ADHD before ASD and 25.6% received a diagnosis of ASD first. Relationships were found between ADHD symptoms and comorbid psychopathology, GI symptoms, and behaviour problems. The outcomes suggest that ADHD is being underestimated as a comorbid disorder of ASD. This may have implications on treatment and interventions for children and adolescents who have a diagnosis of both ASD and ADHD.


Generation and characterization of urokinase receptor-deficient mice.
Mice homozygously deficient for the urokinase-type plasminogen activator (u-PA) receptor (u-PAR-1-) were generated by homologous recombination in D3, embryonic stem cells. The genomic sequences comprising exon 2 through 5 of the u-PAR gene were replaced by the neomycin resistance gene, resulting in inactivation of both u-PAR splice variants. The inactivated u-PAR allele was transmitted via mendelian inheritance, and fertility. Inactivation of u-PAR was confirmed by the absence of binding of rabbit anti-murine u-PAR or of an aminoterminal fragment of murine u-PA (mu-PA.1-48) to u-PAR-1- embryonic fibroblasts and macrophages. u-PAR-1- mice displayed normal lysis of a murine plasma clot injected via the jugular vein. Invasion of macrophages into the peritoneal cavity after thioglycollate stimulation was similar in u-PAR-1- and u-PAR-1- mice. u-PAR-1- peritoneal macrophages had a threefold decreased initial rate of u-PA-mediated plasminogen activation in vitro but degraded extracellular matrix proteins in vitro as efficiently as u-PAR-1- macrophages.


[Perspectives for the clinical application of the results of current neuromorphological studies of the optical nerve lesions and atrophies].
The review presents the analysis of advances in fundamental studies of the optic nerve regeneration and degeneration mechanisms. It is concluded that current experimental morphological investigations of mechanisms of pathogenesis and sanogenesis of the optic nerve atrophies are developing in several major directions. These include: 1) development of techniques for restoration of the integrity of the optic nerve stem, including those that use peripheral nerve grafts; 2) development of measures to decrease the retinal ganglionic cell (RGC) response to injury and to stimulate RGC repair processes; 3) search for the ways for axon growth stimulation in lesioned and undamaged RGC; 4) usage of RGC apoptosis inhibitors; 5) grafting of embryonic retina. Results of the experimental studies are evaluated in the context of their possible application in clinical practice.


[Care for the HIV-infected person].
Early medical intervention in patients with HIV infection is beneficial even in asymptomatic individuals. Medical care in these patients consists of the use of antiretroviral drugs, drugs to prevent opportunistic infections, vaccines and comprehensive psychosocial support. It is important to determine the stage of the natural history of the disease at any given moment. Besides clinical data, the determination of CD4+ T-lymphocytes is useful to make decisions related to the institution of antiretroviral drugs and preventive therapy for opportunistic infections. Present evidence shows a clear benefit of starting antiretroviral drugs in every patient with AIDS or AIDS related complex and also supports the use of these drugs in early stages of the disease. Preventive therapy against Pneumocystis carinii has to be instituted in every patient with CD4 lymphocyte counts below 200/mm3. Prophylactic therapy may also be necessary to prevent tuberculosis, toxoplasmosis and M. avium. It is likely that future studies will show some benefit with the use of additional preventive strategies for other frequent infections such as Cytomegalovirus and Cryptosporidium.


C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients.
The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients' plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I - 0.7089; stage II - 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.


Immunohistological studies with A1-3, a monoclonal antibody to activated human monocytes and macrophages.
A wide variety of monoclonal antibodies (mAb) have now been produced which recognize cell surface antigens on human peripheral blood monocytes. However, few of these mAb demonstrate specificity for monocytes, and fewer still recognize antigens exclusively on monocytes activated by one or more stimuli and/or block specific monocyte functions. The mAb A1-3 binds to lipopolysaccharide (LPS)-stimulated monocytes but not to resting blood monocytes, and inhibits the procoagulant activity of these LPS-activated cells. By using this mAb, we examined the reactivity of monocytes/macrophages (MO) in a broad range of normal and inflammatory tissues by means of a sensitive, four-layer immunoperoxidase technique. Cells of the MO system, in addition to lymphocytes and dendritic cells resident in lymphoid tissues, liver, lung, and other organs, were nonreactive with the A1-3 mAb. In contrast, intense staining of inflammatory MO was found in biopsies from patients with renal allograft rejection, acute glomerulonephritis, or granulomatous diseases. This apparent restriction of A1-3 binding to inflammatory, "activated" MO suggests that A1-3 mAb will be useful for the analysis of MO "activation" in many pathologic processes.


Kinetic characteristics of the excitability-inducing material channel in oxidized cholesterol and brain lipid bilayer membranes.
The kinetic characteristics of the opening and closing of the excitability-inducing material (EIM) channel in oxidized cholesterol and in brain lipid bilayers are compared. The kinetics of the opening and closing of individual ion-conducting channels in bilayers doped with small amounts of EIM are determined from discrete fluctuations in ionic current. The kinetics for approach to steady-state conductance are determined for lipid bilayers containing many channels. Steady-state and kinetic characteristics for the EIM channel incorporated in brain lipid bilayers can be accounted for by the model developed for the EIM channel incorporated in oxidized cholesterol membranes. Relaxation time, calculated from rate constants of single-channel membranes or directly measured in many-channel membranes is strongly temperature dependent, and is always shorter in brain lipid membranes. Changes in temperature do not affect the interaction of the electric field and the open channel, but the open configuration of the EIM channel in brain lipid bilayers is stablized with increasing temperature. The configurational energy difference between the open and closed channel, calculated from temperature studies, is larger in brain lipid bilayers. The energy barrier which separates the two configurations of the channel is larger in oxidized cholesterol bilayers.


Children's roles in tuberculosis treatment regimes: constructing childhood and kinship in urban Zambia.
In Zambia, the burden of HIV-related diseases such as tuberculosis has received substantial international attention. Zambians experience and participate in a range of globally produced programs to manage TB and cure TB sufferers. Guided by WHO's Directly Observed Treatment, Short-course protocol, TB treatment regimens now emphasize adherence to medications as the primary way to achieve cure. This article aims to understand how adherence models enter into the daily lives of children who live with and care for adult TB patients in an area disproportionately affected by the disease. I suggest that children domesticate adherence models, using them as strategies to safeguard identities, relationships, livelihoods, and futures that are increasingly under threat in the age of HIV. They draw on TB treatment and the hope and agency it affords to hold onto a version of childhood in which they are cared for by adults who will advocate for their well-being.


From scientific theory to classroom practice.
The importance of neuroscience in education is becoming widely recognized by both neuroscientists and educators. However, to date, there has been little effective collaboration between the two groups, resulting in the spread of ideas in education poorly based on neuroscience. For their part, educators are often too busy to develop sufficient scientific literacy, and neuroscientists are put off collaborations with risk of overinterpretation of their work. We designed and led a successful 6-month collaborative project between educators and neuroscientists. The project consisted of a series of seminars on topics chosen by both parties such as the neuroscience of attention, learning, and memory and aimed to create a dialog between the two. Here, we report that all teachers found the seminars relevant to their practice and that the majority felt the information was presented in an accessible manner. Such was the success of the project that teachers felt there were direct changes in their classroom practice as a consequence and that the course should be more widely available. We suggest that this format of co-constructed dialog allows for lucrative collaborations between neuroscientists and educators and may be a step to bridging the waters that separate these intrinsically linked disciplines.


The Radial Artery for Percutaneous Coronary Procedures or Surgery?
This article summarizes the current research on the benefits of using the transradial approach for percutaneous procedures and the radial artery as a conduit for coronary artery bypass surgery. Based on the available evidence, the authors provide recommendations for the use of the radial artery in patients undergoing percutaneous or surgical coronary procedures.


The Role of Laser Speckle Imaging in Port-Wine Stain Research: Recent Advances and Opportunities.
Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.


Effects of estrogen on the vascular system.
The cardiovascular protective actions of estrogen are partially mediated by a direct effect on the vessel wall. Estrogen is active both on vascular smooth muscle and endothelial cells where functionally competent estrogen receptors have been identified. Estrogen administration promotes vasodilation in humans and in experimental animals, in part by stimulating prostacyclin and nitric oxide synthesis, as well as by decreasing the production of vasoconstrictor agents such as cyclooxygenase-derived products, reactive oxygen species, angiotensin II, and endothelin-1. In vitro, estrogen exerts a direct inhibitory effect on smooth muscle by activating potassium efflux and by inhibiting calcium influx. In addition, estrogen inhibits vascular smooth muscle cell proliferation. In vivo, 17beta-estradiol prevents neointimal thickening after balloon injury and also ameliorates the lesions occurring in atherosclerotic conditions. As is the case for other steroids, the effect of estrogen on the vessel wall has a rapid non-genomic component involving membrane phenomena, such as alteration of membrane ionic permeability and activation of membrane-bound enzymes, as well as the classical genomic effect involving estrogen receptor activation and gene expression.


Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis.
Fibrosis, a feature of systemic sclerosis (SSc), is more severe in the diffuse compared with the limited disease variant. Interleukin 10 (IL-10) is an anti-inflammatory cytokine which reduces type 1 collagen mRNA levels in human fibroblasts. The 5' flanking region of the IL-10 gene is highly polymorphic, with three single base pair substitutions at position -1082(G/A), -819(C/T) and -592(C/A), which results in differential IL-10 production. The GCC/GCC genotype is associated with high IL-10 production while the ATA/ATA genotype with low production. We postulated that there would be a difference in IL-10 polymorphisms in patients with limited (lSSc) and diffuse (dSSc) disease. Patients with limited (lSSc, n = 89) or diffuse (dSSc, n = 51) disease plus controls (n = 94) were recruited. DNA was isolated from peripheral blood and polymorphisms analysed using amplification refractory mutation system (ARMS) polymerase chain reaction (PCR). dSSc patients were less likely to carry the genotype indicative of high IL-10 production when compared with controls (controls vs dSSc; 29 vs 4%, chi2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, chi2 = 17.5, 5 df, P = 0.002). There was no difference between control and lSSc patients. While there was no difference between controls and lSSc haplotypes, the GCC haplotype distribution did differ significantly between controls and dSSc patients (controls vs dSSc; 54 vs 36%, chi2 = 11.2, 2 df, P = 0.001). A significant difference was also observed between lSSc and dSSc haplotype distribution (lSSc vs dSSc; 48 vs 36%, chi2 = 13.5, 2 df, P < 0.001). We demonstrate that IL-10 genotypes associated with high IL-10 production are under-represented in dSSc. This may have implications in the disease pathology.


Cardiovascular consequences of new-onset hyperglycemia after kidney transplantation.
New-onset diabetes after transplantation (NODAT) is associated with high cardiovascular (CV) risk and reduced patient survival. It is unclear whether this risk is newly acquired or represents preexisting CV disease in patients with this complication. Included are 1146 adults, recipients of first kidney transplants from 1984 to 2008 treated with modern immunosuppressants. One year after transplantation, 29.8% of patients experienced impaired fasting glycemia and 13.4% NODAT. The risk of NODAT related to recipient variables include the following: older age, male gender, higher body mass index, higher pretransplantation glucose and triglyceride levels, and lower high-density lipoprotein level. Increasing fasting glucose levels at 1, 4, or 12 months after transplantation, independent of other factors, related to reduced patient survival (12 months hazard ratio [HR]=1.146 [1.132-1.161], P<0.0001 for 10mg/dL increase in glucose), and this was primarily because of an increase in CV deaths. Hyperglycemia related to all major CV events (MCVE), cardiac (HR=1.113 [1.094-1.132], P<0.0001), vascular (HR=1.168 [1.140-1.197], P<0.0001), and strokes (HR=1.156 [1.123-1.191], P=0.003). These relations were statistically independent of other risk factors. The increased risk of MCVE was noted particularly in patients without MCVE before transplantation (HR=1.145 [1.126-1.165], P<0.0001). Furthermore, among patients with after transplantation MCVE (n=123, 11%), hyperglycemia increases the risk of death (NODAT: HR=2.410 [1.125-5.162], P=0.024). After transplantation hyperglycemia is a strong independent risk factor for MCVE and death, mainly from CV causes. This risk is independent of the presence of CV disease identified before transplantation.


Beta-lactamase Escherichia coli and Staphylococcus aureus isolated from chickens in Nigeria.
The occurrence of beta-lactamase-producing Escherichia coli and Staphylococcus aureus in chickens was investigated. Specimens (n = 1,300) were collected from 400 chickens and were streaked on MacConkey agar plates. From each plate, presumptive growths of organisms were picked and streaked on eosin methylene blue and Baird-Parker agars, respectively. Typical colonies of E. coli and S. aureus with similar morphologies were identified by biochemical tests. Isolates were tested for beta-lactamase production and antimicrobial susceptibilities. Results indicated that 805 E. coli isolates from which 89 (11%) were beta-lactamase-positive and 660 S. aureus from which 58 (8.8%) were beta-lactamase-positive. Both isolates showed a high level of resistance to all twelve antibiotics screened. The increased prevalence of antibiotic resistance amongst bacterial organisms is undoubtedly correlated with the discovery and characterisation of multiple, transferrable resistance determinants, such as beta-lactamases, corresponding to their respective phenotypes. The implications of this for humans when handling and/or consuming chickens and chicken products contaminated with strains of such isolates, is a risk of transferrable multi-drug resistance and a failure of treatment. The results of our study indicated that beta-lactamase-producing E. coli and S. aureus are prevalent in chickens in Nigeria.


Tethering of intercellular adhesion molecule on target cells is required for LFA-1-dependent NK cell adhesion and granule polarization.
Alpha(L)beta(2) integrin (LFA-1) has an important role in the formation of T cell and NK cell cytotoxic immunological synapses and in target cell killing. Binding of LFA-1 to ICAM on target cells promotes not only adhesion but also polarization of cytolytic granules in NK cells. In this study, we tested whether LFA-1-dependent NK cell responses are regulated by the distribution and mobility of ICAM at the surface of target cells. We show that depolymerization of F-actin in NK-sensitive target cells abrogated LFA-1-dependent conjugate formation and granule polarization in primary NK cells. Degranulation, which is not controlled by LFA-1, was not impaired. Fluorescence recovery after photobleaching experiments and particle tracking by total internal reflection fluorescence microscopy revealed that ICAM-1 and ICAM-2 were distributed in largely immobile clusters. ICAM clusters were maintained and became highly mobile after actin depolymerization. Moreover, reducing ICAM-2 mobility on an NK-resistant target cell through expression of ezrin, an adaptor molecule that tethers proteins to the actin cytoskeleton, enhanced LFA-1-dependent adhesion and granule polarization. Finally, although NK cells kept moving over freely diffusible ICAM-1 on a lipid bilayer, they bound and spread over solid-phase ICAM-1. We conclude that tethering, rather than clustering of ICAM, promotes proper signaling by LFA-1 in NK cells. Our findings suggest that the lateral diffusion of integrin ligands on cells may be an important determinant of susceptibility to lysis by cytotoxic lymphocytes.


[The loop-like growth of the vessels and the embryonic morphogenesis of the human intraorganic circulatory system].
Development of the vascular bed during embryogenesis in man occurs through loop-like growth of vessels appearing as multiplication, integration, and morphofunctional transformation of vessel loops. Growth of loops provides for the establishment of transport vessels in organs and tissues, and loop integration leads to the establishment of microcirculation with the appearance of connecting and major capillaries, from which true capillaries and capillary networks are formed. Precapillary arterioles and postcapillary venules can be identified topographically in the capillary networks. Formation of blood microcirculation system is complete when morphofunctional arrangement of integrated and nonintegrated loops takes place with the appearance of arterioles and venule collaterals and arterio-venule anastomoses in the vascular network.


Potassium channel dysfunction in hypothalamic glucose-receptive neurones of obese Zucker rats.
1. We have shown, using intracellular and cell-attached recordings, that glucose-receptive (GR) neurones of obese Zucker rats exhibit abnormal electrophysiological responses to changes in extracellular glucose concentration, whereas GR neurones of lean Zucker and control rats respond normally. 2. In inside-out recordings from obese rat GR neurones it was shown that the 150 pS ATP-sensitive K+ (KATP) and the 160 pS calcium-activated K+ (KCa) channels were absent, whereas both were present in GR neurones of lean Zucker and control rats. 3. The potassium channel most frequently observed in inside-out patches from obese GR neurones was characterized by a conductance of 213 pS, was activated by raising internal calcium and inhibited by application of internal ATP. This channel (which we have termed Kfa) was not observed in lean or control rat GR neurones. 4. Tolbutamide (100 microM) was found to induce no effect or to elicit a small depolarization of obese rat GR neurones in the absence of glucose, in contrast to its clear excitatory actions on control or lean Zucker GR neurones. 5. Intracellular, cell-attached and inside-out recordings from obese rat non-GR neurones showed that there was no alteration in their membrane properties or firing characteristics or in the characteristics of the large-conductance calcium-activated K+ channel (KCa) present in these neurones as compared with lean and control rats. 6. It is concluded that the Kfa channel is specific to GR neurones of obese Zucker rats and that the presence of this channel coupled with the absence of KATP and KCa channels results in the abnormal glucose-sensing response of these neurones.


A procedure for membrane-protein reconstitution and the functional reconstitution of the anion transport system of the human-erythrocyte membrane.
A short procedure for the isolation of band-3 protein, the protein responsible for anion exchange in erythrocytes, in a reasonable degree of purity was developed. Using this protein preparation and a novel procedure for membrane-protein reconstitution, vesicles displaying the basic features of the anion-exchange system of the erythrocyte were obtained. The reconstitution procedure is based on slow direct removal of Triton X-100 from aqueous lipid/detergent solutions. According to the composition of the reconstitution medium, either small single-walled or large multi-walled vesicles are obtained. The procedure conserves protein properties well, as is revealed by the similarity of the rates of SO4(2-) exchange in erythrocytes and reconstituted vesicles when corrected for the relevant volumes. A number of functional features of the exchange system were studied and compared with those of the native membrane.


[Osteoporosis and estrogens].
5 major risk factors for osteoporosis have been identified: age, initial bone density, the menopause, bioavailability of calcium, and sporadic factors. Age appears to be the major determinant of bone mass. During a lifetime, a woman will typically lose 50% of her trabecular bone and 35% of her cortical bone. Bone density is affected by the amount of bone developed during growth, as well as by the subsequent rate of loss. Strong evidence has shown that loss of ovarian function leads to an accelerated phase of bone loss. Bone turnover rates increase, but resorption occurs faster than formation. This acceleration slows with time, reaching the level of the underlying slower phase of bone loss approximately 10 years after the onset of menopause. The role of calcium intake in preventing osteoporosis remains a matter of debate. Other factors shown to affect the risk of osteoporosis include low weight, smoking, alcohol intake, and degree of physical activity. The fact that not all postmenopausal women develop osteoporosis suggest that other, as yet determinant factors may play a role in this condition.


Ultrarapid purification of collagen type I for tissue engineering applications.
Acid-solubilized collagen type I (COL1) can form highly organized, three-dimensional scaffolds for a wide variety of bioengineering and cell culture applications. A rapid COL1 isolation method would be a valuable tool for both basic and translational researchers because conventional techniques require days or weeks to complete, typically use nonhuman animal tissues as a source material, and do not efficiently purify autologous COL1 from small samples. Here, we describe a 3-h method to isolate COL1 from rabbit, lamb, and human skin in sufficient quantities for fabrication of autologously derived tissues by using a rapid agitation technique and incorporating centrifugal filtration units into a traditional isolation procedure. We demonstrate that the purified product is comparable to traditional preparations using polyacrylamide gel electrophoresis, transmission electron microscopy, and collagen content assays. In addition, our COL1 is able to support myogenic cell growth and direct orientation of these cells in vitro. Importantly, this ultrarapid COL1 isolation procedure increases the feasibility of autologous COL1 use in humans as well as overall safety for clinical patients.


Impact of the microgravity environment in a 3-dimensional clinostat on osteoblast- and osteoclast-like cells.
Mechanical unloading conditions result in decreases in bone mineral density and quantity, which may be partly attributed to an imbalance in bone formation and resorption. To investigate the effect of mechanical unloading on osteoblast and osteoclast differentiation, and the expression of RANKL and OPG genes in osteoblasts, we used a three-dimensional (3D) clinostat system simulating microgravity to culture MC3T3-E1 and RAW264.7 cells. Long-term exposure (7 days) of MC3T3-E1 cells to microgravity in the 3D clinostat inhibited the expression of Runx2, Osterix, type I collagen alphaI chain, RANKL and OPG genes. Similarly, 3D clinostat exposure inhibited the enhancement of beta3-integrin gene expression, which normally induced by sRANKL stimulation in RAW264.7 cells. These results, taken together, demonstrate that long-term 3D clinostat exposure inhibits the differentiation of MC3T3-E1 cells together with suppression of RANKL and OPG gene expression, as well as the RANKL-dependent cellular fusion of RAW264.7 cells, suggesting that long-term mechanical unloading suppresses bone formation and resorption.


Comparative evaluation of antibacterial effects of Nd:YAG laser irradiation in root canals and dentinal tubules.
The antibacterial effects of the Nd:YAG laser on contaminated root canals and dentinal tubules were observed as the aim of this study. The samples were inoculated with Streptococcus sanguis (NCTC 7853) and Prevotella intermedia (NCTC 93336), and the effects of Nd:YAG laser were tested on these teeth. The specimens were lased with 1.8 W and 2.4 W Nd:YAG laser for 30 s, and the presence of bacteria in tubules was observed under light microscopy. The 1.8 W laser sterilized the tubules in 86.3% of sections inoculated with S. sanguis, whereas 2.4 W laser sterilized in 98.5% of the sections. Both laser powers sterilized all samples inoculated with P. intermedia. The scanning electron microscopic observations supported the light microscopic findings.


Partial trapeziectomy and pyrocarbon interpositional implant (Pyrodisk) for trapeziometacarpal osteoarthritis in the active working population: outcomes of a 10 years-experience.
The treatment of trapeziometacarpal (TM) osteoarthritis is still debated, as many surgical options are available, and no technique has proven to be superior. Prosthetic treatment in this context has been described since the early 60s. Recently, the use of pyrolytic carbon-based prosthesis has revolutionized arthroplasty surgery in the hand. We performed a retrospective investigation of our surgical management of TM osteoarthritis since 2010 including the study only patients treated with partial trapeziectomy and Pyrodisk implant, with at least 5 years follow-up. After the application of inclusion criteria, 26 patients (6 males and 20 females) were retained. Despite the literature suggesting that implant TM surgery is well suited for older patients, in our experience, the procedure was mainly proposed to the young manual worker, with high demands in terms of thumb strength and stability (mean age of 53 years old, range 37-65). A statistically significant improvement in post-operative DASH, Kapandji and scores was observed. As well, strength measurements, particularly pinch strength and grip strength, increased significantly after the surgery. According to our findings, the Pyrodisk implant provides satisfactory results in terms of thumb strength and stability even in young and active patients and should therefore be considered as a valuable option in selected cases. Meticulous surgical procedure is mandatory in order to avoid complications and should therefore be executed by an expert surgeon. Abbreviation: IV: level of evidence.


Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems.
Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins that can reverse inhibition. Although Escherichia coli encodes 11 toxins with known or putative endoribonuclease activity, the targets of most of these toxins remain poorly characterized. Using a new RNA sequencing (RNA-seq) pipeline that enables the mapping and quantification of RNA cleavage with single-nucleotide resolution, we characterized the targets and specificities of 9 endoribonuclease toxins from E. coli. We found that these toxins use low-information cleavage motifs to cut a significant proportion of mRNAs in E. coli, but not tRNAs or the rRNAs from mature ribosomes. However, all the toxins, including those that are ribosome dependent and cleave only translated RNA, inhibit ribosome biogenesis. This inhibition likely results from the cleavage of ribosomal protein transcripts, which disrupts the stoichiometry and biogenesis of new ribosomes and causes the accumulation of aberrant ribosome precursors. Collectively, our results provide a comprehensive, global analysis of endoribonuclease-based toxin-antitoxin systems in E. coli and support the conclusion that, despite their diversity, each disrupts translation and ribosome biogenesis. IMPORTANCE Toxin-antitoxin (TA) systems are widespread genetic modules found in almost all bacteria that can regulate their growth and may play prominent roles in phage defense. Escherichia coli encodes 11 TA systems in which the toxin is a known or predicted endoribonuclease. The targets and cleavage specificities of these endoribonucleases have remained largely uncharacterized, precluding an understanding of how each impacts cell growth and an assessment of whether they have distinct or overlapping targets. Using a new and broadly applicable RNA-seq pipeline, we carried out a global analysis of 9 endoribonuclease toxins from E. coli. We found that each uses a relatively low-information cleavage motif to cut a large proportion of mRNAs in E. coli, but not tRNAs or mature rRNAs. Notably, although the precise set of targets varies, each toxin efficiently disrupts ribosome biogenesis, primarily by cleaving the mRNAs of ribosomal proteins. In sum, the analyses presented provide new, comprehensive insights into the cleavage specificities and targets of almost all endoribonuclease toxins in E. coli. Despite different specificities, our work reveals a striking commonality in function, as each toxin disrupts ribosome biogenesis and translation.


Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?
The world population is still facing the second wave of the COVID-19 pandemic. Such a challenge requires complicated tools to control, namely vaccines, effective cures, and complementary agents. Here we present one candidate for the role of an effective cure and/or complementary agent: lactoferrin. It is the cross-talking mediator between many organs/cellular systems in the body. It serves as a physiological, immunological, and anti-microbial barrier, and acts as a regulator molecule. Furthermore, lactoferrin has receptors on most tissues cells, and is a rich source for bioactive peptides, particularly in the digestive system. In the past months, in vitro and in vivo evidence has accumulated regarding lactoferrin's ability to control SARS-CoV-2 infectivity in different indicated scenarios. Also, lactoferrin or whey milk (of human or other mammal's origin) is a cheap, easily available, and safe agent, the use of which can produce promising results. Pharmaceutical and/or food supplementary formulas of lactoferrin could be particularly effective in controlling the gastrointestinal COVID-19-associated symptoms and could limit the fecal-oral viral infection transmission, through mechanisms that mimic that of norovirus infection control by lactoferrin via induction of intestinal innate immunity. This natural avenue may be effective not only in symptomatic patients, but could also be more helpful in asymptomatic patients as a main or adjuvant treatment.


Association between CYP7A1 and the risk of proximal colon cancer in Japanese.
Bile acids have long been implicated in the etiology of colorectal carcinogenesis by their genotoxicity as well as cytotoxicity. Cholesterol 7-alfa-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7-alfa-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. Recently, an association between a polymorphism (-204A>C, rs3808607) in CYP7A1 and proximal colon cancer/adenoma has been reported, which was not observed with distal colon or rectal cancer/adenoma. In this case-control study, we examined the association between haplotypes of CYP7A1 and proximal or distal colon/rectal cancer risk in a Japanese population. Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age- and sex-matched non-cancer controls at Aichi Cancer Center. We examined five loci, including rs3808607, and evaluated the impact of haplotype on risk. In locus-specific analyses, we saw no association with rs3808607 for any site. Haplotype analyses revealed that the TAAGG haplotype was positively associated with proximal colon cancer [confounder-adjusted odds ratio: 1.72 (95% confidence interval: 1.10-2.71), p=0.018] but not with distal colon and rectal cancer combined. This association was consistently observed in analyses stratified by potential confounders. Our results indicate that CYP7A1 plays a role in the carcinogenesis of colorectal cancer specifically in the proximal colon. Confirmation of this association in other epidemiologic studies and biological evaluation of the TAAGG haplotype are warranted.


Tomographic near-eye displays.
The ultimate 3D displays should provide both psychological and physiological cues for depth recognition. However, it has been challenging to satisfy the essential features without making sacrifices in the resolution, frame rate, and eye box. Here, we present a tomographic near-eye display that supports a wide depth of field, quasi-continuous accommodation, omni-directional motion parallax, preserved resolution, full frame, and moderate field of view within a sufficient eye box. The tomographic display consists of focus-tunable optics, a display panel, and a fast spatially adjustable backlight. The synchronization of the focus-tunable optics and the backlight enables the display panel to express the depth information. We implement a benchtop prototype near-eye display, which is the most promising application of tomographic displays. We conclude with a detailed analysis and thorough discussion of the display's optimal volumetric reconstruction. of tomographic displays.


Peptidomics Analysis of Milk Protein-Derived Peptides Released over Time in the Preterm Infant Stomach.
Over the course of milk digestion, native milk proteases and infant digestive proteases fragment intact proteins into peptides with potential bioactivity. This study investigated the release of peptides over 3 h of gastric digestion in 14 preterm infant sample sets. The peptide content was extracted and analyzed from milk and gastric samples via Orbitrap tandem mass spectrometry. The relative ion intensity (abundance) and count of peptides in each sample were compared over time and between infants fed milk fortified with bovine milk fortifier and infants fed unfortified milk. Bioactivity of the identified peptides was predicted by sequence homology to known bioactive milk peptides. Both total and bioactive peptide abundance and count continuously increased over 3 h of gastric digestion. After accounting for infant weight, length, and postconceptual age, fortification of milk limited the release of peptides from human milk proteins. Peptides that survived further gastric digestion after their initial release were structurally more similar to bioactive peptides than nonsurviving peptides. This work is the first to provide a comprehensive profile of milk peptides released during gastric digestion over time, which is an essential step in determining which peptides are most likely to be biologically relevant in the infant. Data are available via ProteomeXchange with identifier PXD012192.


Cultural transmission of tool use by Indo-Pacific bottlenose dolphins (Tursiops sp.) provides access to a novel foraging niche.
Culturally transmitted tool use has important ecological and evolutionary consequences and has been proposed as a significant driver of human evolution. Such evidence is still scarce in other animals. In cetaceans, tool use has been inferred using indirect evidence in one population of Indo-Pacific bottlenose dolphins (Tursiops sp.), where particular dolphins ('spongers') use marine sponges during foraging. To date, evidence of whether this foraging tactic actually provides access to novel food items is lacking. We used fatty acid (FA) signature analysis to identify dietary differences between spongers and non-spongers, analysing data from 11 spongers and 27 non-spongers from two different study sites. Both univariate and multivariate analyses revealed significant differences in FA profiles between spongers and non-spongers between and within study sites. Moreover, FA profiles differed significantly between spongers and non-spongers foraging within the same deep channel habitat, whereas the profiles of non-spongers from deep channel and shallow habitats at this site could not be distinguished. Our results indicate that sponge use by bottlenose dolphins is linked to significant differences in diet. It appears that cultural transmission of tool use in dolphins, as in humans, allows the exploitation of an otherwise unused niche.


Specificity determinants for lipids bound to beta-barrel proteins.
The family of proteins accountable for the intracellular movement of lipids is characterized by a 10-stranded beta-barrel that forms an internalized cavity varying in size and binding preferences. The loop connecting beta-strands E and F (the fifth and sixth strands) is the most striking conformational difference between adipocyte lipid binding protein (ALBP; fatty acids) and cellular retinoic acid binding protein type I (CRABP I). A three-residue mutation was made in wild-type (WT)-ALBP [ALBP with a three-residue mutation (EF-ALBP)] to mimic CRABP I. Crystal structures of ligand-free and EF-ALBP with bound oleic acid were solved to resolutions of 1.5 A and 1.7 A, respectively, and compared with previous studies of WT-ALBP. The changes in three residues of one loop of the protein appear to have altered the positioning of the C18 fatty acid, as observed in the electron density of EF-ALBP. The crystallographic studies made it possible to compare the protein conformation and ligand positioning with those found in the WT protein. Although the cavity binding sites in both the retinoid and fatty acid binding proteins are irregular, the ligand atoms appear to favor a relatively planar region of the cavities. Preliminary chemical characterization of the mutant protein indicated changes in some binding properties and overall protein stability.


Multifunctional Chiral Chemically-Powered Micropropellers for Cargo Transport and Manipulation.
Practical applications of synthetic self-propelled nano and microparticles for microrobotics, targeted drug delivery, and manipulation at the nanoscale are rapidly expanding. However, fabrication limitations often hinder progress, resulting in relatively simple shapes and limited functionality. Here, taking advantage of 3D nanoscale printing, chiral micropropellers powered by the hydrogen peroxide reduction reaction are fabricated. Due to their chirality, the propellers exhibit multifunctional behavior controlled by an applied magnetic field: spinning in place (loitering), directed migration in the prescribed direction, capture, and transport of polymer cargo particles. Design parameters of the propellers are optimized by computation modeling based on mesoscale molecular dynamics. It is predicted by computer simulations, and confirmed experimentally, that clockwise rotating propellers attract each other and counterclockwise repel. These results shed light on how chirality and shape optimization enhance the functionality of synthetic autonomous micromachines.


Studying cancer stem cell dynamics on PDMS surfaces for microfluidics device design.
This systematic study clarified a few interfacial aspects of cancer cell phenotypes on polydimethylsiloxane (PDMS) substrates and indicated that the cell phenotypic equilibrium greatly responds to cell-to-surface interactions. We demonstrated that coatings of fibronectin, bovine serum albumin (BSA), or collagen with or without oxygen-plasma treatments of the PDMS surfaces dramatically impacted the phenotypic equilibrium of breast cancer stem cells, while the variations of the PDMS elastic stiffness had much less such effects. Our results showed that the surface coatings of collagen and fibronectin on PDMS maintained breast cancer cell phenotypes to be nearly identical to the cultures on commercial polystyrene Petri dishes. The surface coating of BSA provided a weak cell-substrate adhesion that stimulated the increase in stem-cell-like subpopulation. Our observations may potentially guide surface modification approaches to obtain specific cell phenotypes.


Responding to compliance changes in a lung model during manual ventilation: perhaps volume, rather than pressure, should be displayed.
The standard technique for positive-pressure ventilation is to regulate the breath size by varying the pressure applied to the bag. Investigators have argued that consistency of peak inspiratory pressure is important. However, research shows that excessive tidal volume delivered with excessive pressure injures preterm lungs, which suggests that inspiratory pressure should be varied during times of changing compliance, such as resuscitation of newborns or treatment after surfactant delivery. We modified a computerized lung model (ASL5000 [IngMar Medical, Pittsburgh, PA]) to simulate the functional residual capacity of a 3-kg neonate with apnea and programmed it to change compliance during ventilation. Forty-five professionals were blinded to randomized compliance changes while using a flow-inflating bag, a self-inflating bag, and a T-piece resuscitator. We instructed subjects to maintain a constant inflation volume, first while blinded to delivered volume and then with volume displayed, with all 3 devices. Subjects adapted to compliance changes by adjusting inflation pressure more effectively when delivered volume was displayed. When only pressure was displayed, sensing of compliance changes occurred only with the self-inflating bag. When volume was displayed, adjustments to compliance changes occurred with all 3 devices, although the self-inflating bag was superior. In this lung model, volume display permitted far better detection of compliance changes compared with display of only pressure. Devices for administration of positive-pressure ventilation should display volume rather than pressure.


NH2-Terminal Cleavage of Cardiac Troponin I Signals Adaptive Response to Cardiac Stressors.
Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca2+, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation. Hearts of various species including humans express a stress-induced truncated variant of cardiac troponin I (cTnI-ND) missing the first ~30 amino acids and functionally mimicking the phosphorylated state of cTnI. Studies have demonstrated that upregulation of cTnI-ND potentially represents a homeostatic mechanism as well as an adaptive response in pathophysiology including ischemia/reperfusion injury, beta adrenergic maladaptive activation, and aging. We present evidence showing that cTnI-ND can modify the trigger for hypertrophic cardiomyopathy (HCM) by reducing the Ca2+ sensitivity of myofilaments from hearts with an E180G mutation in α-tropomyosin. Induction of this truncation may represent a therapeutic approach to modifying Ca2+-responses in hearts with hypercontractility or heat failure with preserved ejection fraction.


A morphometric analysis of the lung of a species of bat.
The lungs of five adult Epauleted Fruit-bats (Epomophorus wahlbergi) of mean body weight 96 g were analysed morphometrically. The lung volume per unit body weight was 0.043 cm3/g, the surface area of the tissue barrier (i.e., the effective alveolar surface area) component of the blood-gas pathway per unit body weight was 138 cm2/g, and the surface density of the tissue barrier (surface area of the tissue barrier per unit volume of parenchyma) was 121 mm2/mm3. The harmonic mean thickness of the tissue barrier was between 0.267 and 0.349 micron. The morphometric pulmonary diffusing capacity per unit body weight (DLO2/W) was 0.02 ml O2 per min per mm Hg per g. These values are compared with those of shrews and birds. It is suggested that in bats enlargement of the lungs, small subdivisions of the air spaces, and a thin blood-gas barrier, could be linked with previously reported circulatory adaptations to account for the high oxygen consumption during flight.


[Adrenergic nerve plexuses of heart and adrenal and myocardial catecholamines of spontaneously hypertensive rats under the influence of electromagnetic irradiation in the millimeter range].
Condition of adrenergic cardiac and adrenal nervous plexuses of Kyoto-Wistar Rats (WKY) and spontaneously hypertensive rats (SHR) was examined by quantitative neurohistochemical methods before and after extremely high frequency field (EHF field) influence of "Bayur" microwave therapy apparatus in mode 1 (42,194 MHz frequency, 7.1 mm wavelength) and in mode 3 (53,534 MHz frequency, 5.6 mm wavelength). Reduction of myocardial nervous plexus density and catecholamine luminescence intensity were detected in SHR, as well as decrease of adrenal glands relative weight and catecholamine luminescence intensity in adrenal medulla of SHR, that is indicative of suppression of sympatho-adrenal system of hypertensive animals by EHF field influence in medical operating modes.


Hepatitis C Virus-Associated Acalculous Cholecystitis and Review of the Literature.
Acute acalculous cholecystitis (AAC) is an infrequently encountered clinical condition associated with high morbidity and mortality. Viral infection associated AAC is rare, but it is most commonly associated with Epstein-Barr virus, cytomegalovirus, dengue virus, hepatitis A, hepatitis B, human immunodeficiency virus, disseminated visceral varicella-zoster virus infection, Zika virus, and hepatitis C. We report on a patient who was first diagnosed with a chronic hepatic C infection and subsequently with acalculous cholecystitis.


Proteome databases and other online resources for chloroplast research in Arabidopsis.
Proteomics aimed at addressing sub cellular fractions, such as chloroplasts, are a complex challenge. In the past few years, several studies in different laboratories have identified and, more recently, quantified, thousands of proteins within whole chloroplasts or chloroplast fractions. A considerable number of these studies are available for querying, using online resources, such as databases containing the proteins identified, encoding genes, acquired spectra, and phosphopeptides. The main purpose of this review is to identity and highlight useful features of these online resourses, mainly focused in proteomics databases related to chloroplast research in Arabidopsis thaliana. Several web sites were consulted. Among them, 11 were selected and discussed herein. The databases were classified into Plastid Databases, General Organelle Proteome Databases, and General Arabidopsis Proteome Databases. Special care was taken to present information regarding protein identification, protein quantification, and data integration. A selected list of online resources is presented in two tables. The databases analyzed are a useful source of information for researchers in the plastid organelle and plant proteomics fields.


GPI7 affects cell-wall protein anchorage in Saccharomyces cerevisiae and Candida albicans.
Glycosylphosphatidylinositol (GPI)-anchoring represents a mechanism for attaching proteins to the cell surface of all eukaryotic cells. Two localizations of GPI proteins have been observed in the yeasts Saccharomyces cerevisiae and Candida albicans: plasma membrane and cell wall. The signals and the mechanisms involved in this differential targeting are presently not well understood. Here several cell-wall-related phenotypes of a gpi7/las21 deletion are described, where GPI7/LAS21 encodes a GPI-anchor-modifying activity. In both organisms, the structure and composition of the cell wall was modified, with a clear increase in chitin deposition. Cell-wall-targeted proteins accumulated in the growth medium, whereas the protein content of the cell wall decreased significantly, suggesting inefficiency of the covalent linkage. The level of plasma-membrane-targeted GPI proteins was not affected. Sequence analyses revealed that gene families involved in the addition of phosphoethanolamines to the core GPI anchor are highly conserved between eukaryotes, with the exception of the Gpi7 family which seems to be fungus-specific. These data are compatible with the notion that the phosphoethanolamine added by Gpi7 protein to the GPI anchor is a key factor in the covalent linkage of cell-wall proteins to fungal cell-wall components.


S-cone psychophysics.
We review the features of the S-cone system that appeal to the psychophysicist and summarize the celebrated characteristics of S-cone mediated vision. Two factors are emphasized: First, the fine stimulus control that is required to isolate putative visual mechanisms and second, the relationship between physiological data and psychophysical approaches. We review convergent findings from physiology and psychophysics with respect to asymmetries in the retinal wiring of S-ON and S-OFF visual pathways, and the associated treatment of increments and decrements in the S-cone system. Beyond the retina, we consider the lack of S-cone projections to superior colliculus and the use of S-cone stimuli in experimental psychology, for example to address questions about the mechanisms of visually driven attention. Careful selection of stimulus parameters enables psychophysicists to produce entirely reversible, temporary, "lesions," and to assess behavior in the absence of specific neural subsystems.


The Irish tobacco industry position on price increases on tobacco products.
To examine what the tobacco industry in Ireland says to government on tobacco price, and what it does. The annual government budgetary and tobacco trade, tax/price increases on cigarettes (2000-2010) and pre-budget submissions from the tobacco industry were analysed. Price increased from €4.77 in 2000 to €8.55 at the end of 2010, 64.0% of the increase was government imposed and 36.0% was imposed by the tobacco trade. The tobacco industry consistently urged government not to increase taxes as this would increase smuggling and contraband tobacco products. However, the tobacco industry increased price every year. There is significant disparity in what the tobacco industry says to government and how it behaves with respect to tobacco price. It is important that tobacco control advocates have access to such data and underscores the importance of strong guidelines for Article 5.3 of the Framework Convention on Tobacco Control.


In vivo platelet redistribution and acute transient thrombocytopenia after eptifibatide injection in baboons.
The occurrence of thrombocytopenia has been reported during clinical eptifibatide (Integrilin) therapy, but the exact mechanism is not yet established to explain the varied duration and severity of thrombocytopenia associated with glycoprotein (GP) IIb/IIIa inhibitors. We assessed the redistribution of platelets in juvenile baboons during acute transient thrombocytopenia that was observed after eptifibatide injection. Eptifibatide was administered intravenously to eight baboons by infusion at 20 microg/kg/min or a bolus injection of 10 mg. Platelet distribution was measured with a gamma scintillation camera using 111In-labeled autologous platelets. Platelet function and GP IIb/IIIa receptor inhibition were evaluated using the Plateletworks system. The effects of pretreatment with abciximab (0.4 mg/kg) or human immunoglobulin concentrate (0.75 g/kg) were also investigated. Eptifibatide, administered as an infusion or a bolus, caused transient thrombocytopenia with uptake of platelets predominantly by the liver. The recovery of platelet aggregation was associated with the re-entry of platelets from the liver into the systemic circulation. Pretreatment with either abciximab (0.4 mg/kg) or human intravenous immunoglobulin (IVIG, 0.75 g/kg) attenuated eptifibatide-induced thrombocytopenia and the hepatic uptake of radiolabeled platelets. Acute thrombocytopenia after eptifibatide injection was caused by the transient redistribution of platelets to the liver. Attenuation of the decrease in platelet count and hepatic sequestration by abciximab and IVIG suggests that thrombocytopenia may have been caused by ligand-induced binding site antigen induction and recognition by the reticuloendothelial system.


Infant survival and litter size in primigravid and multigravid Galagos.
Eighteen years of birth records for three species of Galago at the Duke University Primate Center were examined to determine the effect of gravidity status on neonatal mortality and litter size. Multiparous Galago senegalensis moholi and G crassicaudatus, but not G garnettii, had significantly higher infant survival rates. Gravidity status had no effect on the percentage of multiple births for any of the three species of Galago.


Constraints on food choices of women in the UK with lower educational attainment.
Women of lower educational attainment have less balanced and varied diets than women of higher educational attainment. The diets of women are vital to the long-term health of their offspring. The present study aimed to identify factors that influence the food choices of women with lower educational attainment and how women could be helped to improve those choices. We conducted eight focus group discussions with women of lower educational attainment to identify these factors. We contrasted the results of these discussions with those from three focus group discussions with women of higher educational attainment. Southampton, UK. Forty-two white Caucasian women of lower educational attainment and fourteen of higher educational attainment aged 18 to 44 years. The dominant theme in discussions with women of lower educational attainment was their sense that they lacked control over food choices for themselves and their families. Partners and children exerted a high degree of control over which foods were bought and prepared. Women's perceptions of the cost of healthy food, the need to avoid waste, being trapped at home surrounded by opportunities to snack, and having limited skill and experience with food, all contributed to their sense they lacked control over their own and their family's food choices. An intervention to improve the food choices of women with lower educational attainment needs to increase their sense of control over their diet and the foods they buy. This might include increasing their skills in food preparation.


[Clinical efficiency of the use of interferon inductors in surgical patients].
The authors describe their experience in using cycloferon in 27 patients with pyoseptic abdominal pathology. For comparative evaluation of the efficacy of the immunomodulator, they examined 34 patients who received conventional drug therapy. Immunomodulatory therapy was performed, by taking into account the data on the immune status and severity rated by the SIRS and SAPS. Indications for immunomodulatory therapy were defined. The results of immunomodulation suggest that the use of cycloferon in the complex therapy of patients with pyoseptic abdominal diseases makes it possible to enhance the efficiency of treatment and to reduce the number of postoperative complications.


Evaluation of third treatment week as temporal window for assessing responsiveness on repeated FDG-PET-CT scans in Non-Small Cell Lung Cancer patients.
Early assessment of tumour response to treatment with repeated FDG-PET-CT imaging has potential for treatment adaptation but it is unclear what the optimal time window for this evaluation is. Previous studies indicate that changes in SUVmean and the effective radiosensitivity (αeff, accounting for uptake variations and accumulated dose until the second FDG-PET-CT scan) are predictive of 2-year overall survival (OS) when imaging is performed before radiotherapy and during the second week. This study aims to investigate if multiple FDG-PET-derived quantities determined during the third treatment week have stronger predictive power. Twenty-eight lung cancer patients were imaged with FDG-PET-CT before radiotherapy (PET1) and during the third week (PET2). SUVmean, SUVmax, SUVpeak, MTV41%-50% (Metabolic Tumour Volume), TLG41%-50% (Total Lesion Glycolysis) in PET1 and PET2 and their change (), as well as average αeff (α¯eff) and the negative fraction of αeff values [Formula: see text] ) were determined. Correlations were sought between FDG-PET-derived quantities and OS with ROC analysis. Neither SUVmean, SUVmax, SUVpeak in PET1 and PET2 (AUC = 0.5-0.6), nor their changes (AUC = 0.5-0.6) were significant for outcome prediction purposes. Lack of correlation with OS was also found for α¯eff (AUC = 0.5) and [Formula: see text] (AUC = 0.5). Threshold-based quantities (MTV41%-50%, TLG41%-50%) and their changes had AUC = 0.5-0.7. P-values were in all cases ≫0.05. The poor OS predictive power of the quantities determined from repeated FDG-PET-CT images indicates that the third week of treatment might not be suitable for treatment response assessment. Comparatively, the second week during the treatment appears to be a better time window.