Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells.
Adverse effects, nephrotoxicity and hepatotoxicity, of anticancer drugs such as cisplatin have limited the usage for cancer therapy. Therefore, development or identification of supplement agents in anticancer drugs is attractive to reduce side effects and enhance antitumor activity. Here, we found that decursin isolated from Angelica gigas showed protective effects of cisplatin-induced damage in normal human primary renal epithelial cells (HRCs). We found that decursin significantly blocked cisplatin-induced cytotoxicity by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HRCs. Further, we found that decursin inhibited sub-G1 and cell death by suppression of cleavage of caspase-3, -9 and poly(ADP-ribose) polymerase (PARP) induced by cisplatin treatment in HRCs. Importantly, decursin effectively restored the activities of Cu/Zn superoxide dismutase (SOD), catalase and glutathione peroxidase in cisplatin-treated HRCs. Taken together, our findings demonstrate that decurcin prevents cisplatin-induced cytotoxicity and apoptosis through the activation of antioxidant enzymes in HRCs and suggest further that combination of decursin might suppressed adverse effects of anticancer drugs in cancer patients.


Design, development and evaluation of a resistor-based multiplexing circuit for a 20×20 SiPM array.
One technical challenge in developing a large-size scintillator detector with multiple Silicon Photomultiplier (SiPM) arrays is to read out a large number of detector output channels. To achieve this, different signal multiplexing circuits have been studied and applied with different performances and cost-effective tradeoffs. Resistor-based multiplexing circuits exhibit simplicity and signal integrity, but also present the disadvantage of timing shift among different channels. In this study, a resistor-based multiplexing circuit for a large-sized SiPM array readout was developed and evaluated by simulation and experimental studies. Similarly to a multiplexing circuit used for multi-anode PMT, grounding and branching resistors were connected to each SiPM output channel. The grounding resistor was used to simultaneously reduce the signal crosstalk among different channels and to improve timing performance. Both grounding and branching resistor values were optimized to maintain a balanced performance of the event energy, timing, and positioning. A multiplexing circuit was implemented on a compact PCB and applied for a flat-panel detector which consisted of a 32×32 LYSO scintillator crystals optically coupled to 5×5 SiPM arrays for a total 20×20 output channels. Test results showed excellent crystal identification for all 1024 LYSO crystals (each with 2×2×30 mm3 size) with 22Na flood-source irradiation. The measured peak-to-valley ratio from typical crystal map profile is around 3:1 to 6.6:1, an average single crystal energy resolution of about 17.3%, and an average single crystal timing resolution of about 2 ns. Timing shift among different crystals, as reported in some other resistor-based multiplexing circuit designs, was not observed. In summary, we have designed and implemented a practical resistor-based multiplexing circuit that can be readily applied for reading out a large SiPM array with good detector performance.


Stroke Prevents Exercise-Induced Gains in Bone Microstructure But Not Composition in Mice.
Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study, we use a mild-moderate middle cerebral artery occlusion model to determine the effects of ischemic stroke without bedrest on bone microstructure, dynamic bone formation, and tissue composition. Twenty-seven 12-week-old male C57Bl/6J mice received either a stroke or sham surgery and then either received daily treadmill exercise or remained sedentary for 4 weeks. All mice were ambulatory immediately following stroke, and limb coordination during treadmill exercise was unaffected by stroke, indicating similar mechanical loading across limbs for both stroke and sham groups. Stroke did not directly detriment microstructure, but exercise only stimulated adaptation in the sham group, not the stroke group, with increased bone volume fraction and trabecular thickness in the sham distal femoral metaphysis. Stroke differentially decreased cortical area in the distal femoral metaphysis for the affected limb relative to the unaffected limb, as well as endosteal bone formation rate in the affected tibial diaphysis. Although exercise failed to improve bone microstructure following stroke, exercise increased mineral-to-matrix content in stroke but not sham. Together, these results show that stroke inhibits exercise-induced changes to femoral microstructure but not tibial composition, even without changes to gait. Similarly, affected-unaffected limb differences in cortical bone structure and bone formation rate in ambulatory mice show that stroke affects bone health even without bedrest.


Towards Intelligent, Multidimensional Context-Aware Personalised Healthcare and Wellness Support Services.
Healthcare and wellness support that consider context within different dimensions can lead to intelligent, personalised recommendations that will more likely be accepted and acted upon by consumers. In this paper, we look at the main components of traditional personalised healthcare and wellness support services, and identify some of the challenges that should be addressed in creating a more intelligent and efficient solution. Our contribution lies in defining away forward in terms of designing such a solution.


Fatty acid metabolism in hearts containing elevated levels of CoA.
Palmitate metabolism was determined in isolated perfused hearts containing elevated levels of coenzyme A (CoA). CoA levels were elevated by perfusing hearts with Krebs-Henseleit buffer containing 0.1 mM cysteine, 0.2 mM dithiothreitol, 15 microM pantothenic acid, and no energy substrate. After 45 min, CoA levels had increased from 537 +/- 14 to 818 +/- 44 nmol/g dry wt. When these hearts containing high CoA were subsequently perfused as working hearts with buffer containing 11 mM glucose and 1.2 mM palmitate, long chain acyl CoA levels increased (94 +/- 5-305 +/- 6 nmol/g dry wt). Oxidation of exogenous palmitate (as measured by 14CO2 production from [U-14C]palmitate) was significantly depressed in hearts containing elevated CoA levels. This apparent reduction in fatty acid oxidation was not due to increased glucose or glycogen utilization. When the concentration of palmitate was decreased to 0.4 mM, acyl CoA levels increased much less, and the apparent rate of [14C]palmitate oxidation was unaffected by elevated CoA. Hearts containing high CoA also incorporated [14C]palmitate into triacylglycerols to a greater extent than did control hearts. To determine whether the apparent decrease in exogenous palmitate oxidation resulted from an increased utilization of unlabeled endogenous triacylglycerol fatty acid, [14C]palmitate specific activity was measured in myocardial acylcarnitine. The specific activity of this pool of fatty acid was similar in both control hearts and hearts containing elevated CoA. Thus dilution of the total cellular [14C]acyl carnitine by triacylglycerol hydrolysis was not sufficient to account for the decrease in [U-14C]palmitate oxidation. The possibility that a small pool of rapidly turning over acyl carnitine becomes dilated is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)


[Brain hypometabolism in patients with mesial-temporal sclerosis demonstrated by FDG-PET].
The purpose of this study was to evaluate the extent of brain hypometabolism in patients with mesial-temporal sclerosis (MTS). This retrospective study included 21 patients who had medically refractory complex partial seizures and were selected for surgical therapy after a comprehensive evaluation which included surface EEG recordings and neuroimaging studies (PET, SPECT and MRI). All patients were subjected to surgical intervention and had an histopathological confirmation of MTS. A semi-quantitative analysis of the PET images was performed using regions of interest in the following structures: frontal, parietal and occipital lobes, basal ganglia, thalami, cerebellum and three different regions in the temporal lobes, which included medial, inferior and lateral cortices. An asymmetry index (AI) was calculated, comparing the counts per pixel in the homologous structures in both brain hemispheres. The AI of the different structures were then correlated. A significant correlation was demonstrated between the AI of the medial temporal cortices and the frontal lobe, parietal lobe, basal ganglia and thalami (r = 0.72, 0.62, 0.47 and 0.47 respectively with p < 0.05 ). Within the temporal lobe, highly significant correlations were demonstrated among the structures (as high as 0.86 between temporo-medial and temporo-inferior). These data indicated that hypometabolism extends beyond the epileptogenic focus in the temporal lobe in patients with complex partial seizure related to MTS. The metabolism in the medial portion of the temporal lobe is more correlated with the metabolism in the frontal lobe than with those of the others brain structures outside the temporal lobe. The pathophysiological mechanisms of hypometabolism remain controversial.


Atrial flutter with 1:1 conduction in undiagnosed Wolff-Parkinson-White syndrome.
Atrial flutter with 1:1 atrioventricular conduction via an accessory pathway is an uncommon presentation of Wolff-Parkinson-White syndrome not previously reported in the emergency medicine literature. Wolff-Parkinson-White syndrome, a form of ventricular preexcitation sometimes initially seen and diagnosed in the emergency department (ED), can present with varied tachydysrhythmias for which certain treatments are contraindicated. For instance, atrial fibrillation with preexcited conduction needs specific consideration of medication choice to avoid potential degeneration into ventricular fibrillation. We describe an adult female presenting with a very rapid, regular wide complex tachycardia successfully cardioverted in the ED followed by a normal electrocardiogram (ECG). Electrophysiology study confirmed atrial flutter with 1:1 conduction and revealed an accessory pathway consistent with Wolff-Parkinson-White syndrome, despite lack of ECG findings of preexcitation during sinus rhythm. Why should an emergency physician be aware of this? Ventricular tachycardia must be the first consideration in patients with regular wide complex tachycardia. However, clinicians should consider atrial flutter with 1:1 conduction related to an accessory pathway when treating patients with the triad of very rapid rate (>250 beats/min), wide QRS complex, and regular rhythm, especially when considering pharmacologic treatment. Emergency physicians also should be aware of electrocardiographically concealed accessory pathways, and that lack of delta waves does not rule out preexcitation syndromes such as Wolff-Parkinson-White syndrome.


Plantago ovata: Clinical study of overuse.
The objective of the study was to undertake evidence-base study to evaluate clinical manifestation of the over-estimated use of herbal drug Plantago ovata and to compare it with placebo for the efficacy and adverse effects. The patients of both genders were included. Blood urea, creatinine, ALT, Serum B12, CP, ESR and liver function tests were performed. The data was statistically analyzed in both groups for differential symptomatology. In anorexia test verses control results showed that Plantago ovata husk and placebo showed the affected ratio as 81 percent and 50 percent, correspondingly. Whereas in clinical performance of heart burning, pain in epigastrium, low libido, body pain, dyspepsia, fever, burning sensation in palm and sole in test drug showed affected response as adverse effect 90%, 88% and as control drug, 36%, 29%, 22%, 25%, 38%, 30%, 33%, 57%, respectively. The results were highly marked in test drug i.e. in comparison with placebo. This is clearly evident from data analysis that effect observed in test arm is far more superior hence null hypothesis was rejected clearly. Similarly serological and biochemical reports study i.e. (ALT, Vit. B1 and Vit A) revealed that there is no hepatotoxic and neurotoxic effect found in both the drugs.


Elucidation of the catalytic mechanism of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase using QM/MM calculations.
The folate pathway is a recognized intervention point for treating parasitic and bacterial infections in humans. However, the efficacy of treatments targeting dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) has reduced due to disease-related mutations. This has prompted interest in other enzyme targets on this clinically validated pathway, including 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK). A challenge in the design of molecules to target this enzyme is that the precise mechanism of the reaction and the role of the active site residues are not fully understood. In this study, we report the first theoretical analysis of the catalytic pathway of the natural substrate using hybrid quantum mechanical/molecular mechanical (QM/MM) methods. The reaction profiles associated with three proposed general bases have been investigated, as well as the profile for two mutant enzymes, namely R92A and R82A. We identified R92 as the general base in the wildtype reaction. The predicted barriers are in good agreement with the observed experimental kcat values obtained for wildtype and mutant proteins.


Stem cell based therapy for skeletal muscle diseases.
The use of stem cells to repair and replace damaged skeletal muscle cells in chronic, debilitating muscle diseases such as the muscular dystrophies holds great promise. Different stem cell populations, both of embryonic and adult origin display the potential to generate skeletal muscle cells and have been studied in animal models of muscular dystrophy. These include muscle derived satellite cells; bone marrow derived mesenchymal stem cells, muscle or bone marrow side population cells, circulating CD133+ cells and cells derived from blood vessel walls such as mesoangioblasts or pericytes. The design of effective stem cell based therapies requires a detailed understanding of the molecules and signaling pathways which determine myogenic lineage commitment and differentiation. We discuss the great strides that have been made in delineating these pathways and how a better understanding of muscle stem cell biology has the potential to lead to more effective stem cell based therapies for skeletal muscle regeneration for devastating muscle diseases.


cDNA TRAP display for rapid and stable in vitro selection of antibody-like proteins.
We developed a cDNA TRAP display for the rapid selection of antibody-like proteins in various conditions. By modifying the original puromycin linker in the TRAP display, a monobody was covalently attached to the cDNA. As a proof-of-concept, we demonstrated a rapid model selection of an anti-EGFR1 monobody in a solution containing ribonuclease.


Host-etiological agent interactions in intranasally and intraperitoneally induced Cryptococcosis in mice.
Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 10(3) viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.


Auto-oxidation and oligomerization of protein S on the apoptotic cell surface is required for Mer tyrosine kinase-mediated phagocytosis of apoptotic cells.
Prompt phagocytosis of apoptotic cells prevents inflammatory and autoimmune responses to dying cells. We have previously shown that the blood anticoagulant factor protein S stimulates phagocytosis of apoptotic human B lymphoma cells by human monocyte-derived macrophages. In this study, we show that protein S must first undergo oxidative activation to stimulate phagocytosis. Binding of human protein S to apoptotic cells or to phosphatidylserine multilamellar vesicles promotes auto-oxidation of Cys residues in protein S, resulting in covalent, disulfide-linked dimers and oligomers that preferentially bind to and activate the human Mer tyrosine kinase (MerTK) receptor on the macrophages. The prophagocytic activity of protein S is eliminated when disulfide-mediated oligomerization is prevented, or when MerTK is blocked with neutralizing Abs. Protein S oligomerization is independent of phospholipid oxidation. The data suggest that membranes containing phosphatidylserine serve as a scaffold for protein S-protein S interactions and that the resulting auto-oxidation and oligomerization is required for the prophagocytic activity of protein S. In this way, apoptotic cells facilitate their own uptake by macrophages. The requirement for oxidative modification of protein S can explain why this abundant blood protein does not constitutively activate MerTK in circulating monocytes and tissue macrophages.


Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of [2'-(14)C]nicotine.
Concentrations of nicotine, cotinine, and nornicotine in brain and blood following both intermittent and continuous administration of [2'-(14)C]nicotine to rats were determined to assess nicotine metabolite accumulation in brain following repeated nicotine administration. For intermittent studies, rats were administered s.c. 1 to 10 doses of nicotine (0.3 mg/kg, 15 or 25 microCi of [2'-(14)C]nicotine; 30-min interinjection interval). For continuous administration studies, rats were implanted s.c. with an osmotic minipump delivering nicotine (0.8 mg/kg/day, 25 or 50 microCi of [2'-(14)C]nicotine for 1-21 days). Whole brain and trunk blood was collected. The concentration of [2'-(14)C]nicotine and its metabolites was determined via high-pressure liquid radiochromatography. Brain concentrations of nicotine, cotinine, and nornicotine increased 2-, 12-, and 9-fold, respectively, following 10 injections, reaching a plateau following the fifth injection. Brain blood ratios indicate an enhanced preferential distribution of nornicotine to brain with increasing numbers of injections. Across the 21-day period of continuous infusion, blood nicotine and nornicotine concentrations remained relatively constant, whereas concentrations in brain increased approximately 4-fold. Generally, cotinine concentrations in brain and blood did not change across the infusion period. Brain/blood ratios indicate an increase in nicotine distribution into brain across days of nicotine infusion. Results demonstrate that both nicotine and its metabolites accumulate in brain following repeated nicotine administration, and indicate that brain nicotine concentration can not be extrapolated from plasma cotinine or nicotine concentrations. Thus, nornicotine accumulation following repeated nicotine administration suggests that this metabolite plays a contributory role in the neuropharmacological effects of nicotine.


The enhanced removal and phytodegradation of sodium dodecyl sulfate (SDS) in wastewater using controllable water hyacinth.
Surfactant is an emerging and popular pollutant in both rural and urban areas and its treatment efficacy by phytoremediation is rarely reported. Water hyacinth was utilized to clean anionic surfactant sodium dodecyl sulfate (SDS) in water and its growth and physiological activities were regulated with Chromolaena odorata L. extract. SDS was effectively removed from the water and then transferred to both root and aerial part of water hyacinth. Part of SDS was converted into low-molecular weight degradation intermediates by the hydrogen abstraction reactions in water hyacinth. The removal efficiency and the degradation of SDS were evidently strengthened accompanying with enhanced root activity and ascorbate peroxidase (APX) activity in the presence of Chromolaena odorata L. extract. Meanwhile, the growth of water hyacinth was effectively controlled, exhibiting low-growth rate (≤0.036 g.day-1). Furthermore, the root was considered as the major organ to degrade SDS, which was correlated to the remarkable increase in APX activity and a slight increase in root activity under both SDS and extract stress. In conclusion, water hyacinth managed with Chromolaena odorata L. extract should be proposed as an eco-friendly biotechnical treatment for the surfactant.


Effects of physical training of the dominant arm on ipsilateral radial artery distensibility and structure.
Exercise training induces cardiovascular changes that are both generalized and restricted to the microcirculation of the tissues more actively involved in the exercise itself. Whether the local effect of exercise extends to larger arteries is unknown, however. In the right and left upper limb of 17 right-handed subjects performing an asymmetric training of the upper limbs (hammer throwers and baseball players) and 16 age-matched sedentary controls, we continuously measured radial artery diameter, distensibility and wall thickness by an echotracking and a beat-to-beat finger blood pressure device. Arterial distensibility was calculated by the arctangent model of Langewouters and expressed as continuous values from diastolic to systolic blood pressure. Measurements were made: (1) in baseline conditions; (2) after release from prolonged proximal ischaemia; and (3) after an increase in radial artery blood flow caused by a short (4 min) distal ischaemia to determine the endothelial involvement in the training-induced change in arterial distensibility. In athletes the radial artery distensibility was markedly greater in the right than in the left arm, the latter showing values slightly greater than those seen in the two arms of sedentary subjects. In both arms and groups radial artery distensibility increased markedly after prolonged ischaemia, the between arm and group differences being preserved, however. The radial artery response to distal short ischaemia was, on the other hand, similar in the two arms of the athletes, although greater in these subjects than in the sedentary ones. Radial artery wall thickness was greater in the trained than in the untrained arm of athletes, both values being greater than in sedentary subjects. Asymmetrical training of the upper limbs is accompanied by a greater distensibility of the middle-sized arteries of the more trained side. This is not associated with asymmetrical changes in endothelial structure or function. It is associated with a greater wall thickness in the trained side, suggesting that, at least in part, a training-induced asymmetrical change in wall structure (possibly with a predominance of more distensible tissues such as elastine and smooth muscle) is responsible.


Transtrochanteric rotational osteotomy for late-onset Legg-Calve-Perthes disease.
The pathology of late-onset Legg-Calve-Perthes disease (LCPD) is similar to that of avascular necrosis of the femoral head in adult and is associated with poorer prognosis of the hip. The optimal treatment for this condition is still controversial. The purpose of this study was to evaluate the long-term clinical results of the transtrochanteric rotational osteotomy for the patients with LCPD onset at more than 9 years of age. Individuals included 14 hips in 13 cases with the mean age at onset of the disease and operation of 10 years 9 months and 12 years. Average follow-up periods were 12 years. All cases were resistant to the conservative treatments and did not have our indications for varus osteotomy. Clinical results were evaluated using Merle d'Aubigne Postel score and the modified Stulberg criteria. Average Merle d'Aubigne Postel score at the final follow-up was 16.2 points ranging from 12 to 18 points. All patients did not have additional treatment except nail removal. Stulberg class II, III, and IV were obtained in 5, 2, and 7 hips, respectively. More spherical femoral head was obtained in patients with less head involvement and more bone preservation or new bone formation at posterior pillar. Three hips showed slight narrowing of joint space without severe osteoarthritic changes. Transtrochanteric rotational osteotomy is an effective procedure to salvage the hips of the late-onset LCPD. Amount of head involvement, posterior and lateral pillar had influences on the surgical outcomes.


The metabolism of acetamidothiazoles in the rat. 2-acetamido-4-chloromethylthiazole.
2-Acetamido-4-chloromethylthiazole is metabolized in the rat to (2-acetamido-4-thiazolylmethyl)mercapturic acid and 2-acetamidothiazole-4-carboxylic acid. 2-Acetamido-4-methylthiomethylthiazole and the corresponding sulphoxide and sulphone are also produced as minor metabolites. The identification of the metabolites is described and their formation investigated. Quantitative results on the excretion of the metabolites labelled with (14)C are reported.


The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer.
Parthenolide, a sesquiterpene lactone, shows antitumor activity in vitro, which correlates with its ability to inhibit the DNA binding of the antiapoptotic transcription factor nuclear factor kappaB (NF-kappaB) and activation of the c-Jun NH(2)-terminal kinase. In this study, we investigated the chemosensitizing activity of parthenolide in vitro as well as in MDA-MB-231 cell-derived xenograft metastasis model of breast cancer. HBL-100 and MDA-MB-231 cells were used to measure the antitumor and chemosensitizing activity of parthenolide in vitro. Parthenolide was effective either alone or in combination with docetaxel in reducing colony formation, inducing apoptosis and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1 in vitro. In an adjuvant setting, animals treated with parthenolide and docetaxel combination showed significantly enhanced survival compared with untreated animals or animals treated with either drug. The enhanced survival in the combination arm was associated with reduced lung metastases. In addition, nuclear NF-kappaB levels were lower in residual tumors and lung metastasis of animals treated with parthenolide, docetaxel, or both. In the established orthotopic model, there was a trend toward slower growth in the parthenolide-treated animals but no statistically significant findings were seen. These results for the first time reveal the significant in vivo chemosensitizing properties of parthenolide in the metastatic breast cancer setting and support the contention that metastases are very reliant on activation of NF-kappaB.


The association between bereavement and biomarkers of inflammation.
Bereavement is a major life event that has been associated with a range of negative health outcomes. To assess whether levels of inflammation markers and cortisol vary significantly by bereavement status and/or number of recent bereavements. The study was based on a secondary analysis of data from the Midlife in the United States (MIDUS) II biomarkers project. After excluding participants suffering from conditions which directly affect immune functions, 529 participants were included (age 34-84 years), of whom 260 experienced the death of a person close to them 5-63 months prior to assessment. Levels of interleukin 6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-I), Soluble E-selectin (sE-selectin) and cortisol were examined controlling for demographic and health characteristics. Bereaved respondents had higher levels of inflammatory biomarkers IL-6 and sE-selectin, but not CRP and sICAM-I than the non-bereaved. Number of recent bereavements significantly predicted levels of IL-6 in the unadjusted and adjusted regression models. Body Mass Index (BMI) and number of chronic conditions partially mediated the association between number of bereavements and IL-6 levels. Number of recent bereavements is associated with higher levels of inflammation, particularly among individuals with higher BMI and/or chronic health problems.


[Data on liver enzyme and histological changes caused by intermittent clampings of the hepatoduodenal ligament in an experimental model].
Intermittent compression of the structures of the hepatoduodenal ligament, is often performed during liver surgery. As a result, changes in hepatic blood supply and consequent reperfusion induced tissue damages will develop. Ischemia-reperfusion injury, which occur in local and distant regions, influence outcome of hepatic surgery, and it is in close correlation with the duration of hypoxia during the intervention. In animal model the effect of Baron/Pringle manoeuvre was investigated in terms of changes in liver function tests and histology. The study was carried out on 12 Beagle dogs, clamping of the hepatoduodenal ligament for 3×15 minutes then half an hour reperfusion was performed followed by blood and tissue sampling. Significant histological changes were observed both in the liver as well as the small intestine. In terms of liver function changes, GPT elevation occurred the earliest, GOT and LDH were also increased at the end of the 30 minutes reperfusion. In this animal model, the third 15 minutes compression turned out to be too long. Elevation in GPT levels was the most sensitive marker.


Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly).
To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality. Cohort analytic study of data from randomized placebo-controlled double-blind clinical trial of antihypertensive therapy. Depressive symptoms were assessed semi-annually with the Center for Epidemiological Studies-Depression (CES-D) scale during an average follow-up of 4.5 years. Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program. Generally healthy men and women aged 60 years or older randomized to active antihypertensive drug therapy or placebo who were 70% white and 53% women and had follow-up CES-D scores and no outcome events during the first 6 months (N=4367). All-cause mortality, fatal or nonfatal stroke, or myocardial infarction. Baseline depressive symptoms were not related to subsequent events; however, an increase in depression was prognostic. Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable, controlling for multiple covariates, indicated a 25% increased risk of death per 5-unit increase in the CES-D score (relative risk [RR], 1.25;95% confidence interval [CI], 1.15 to 1.36). The RR for stroke or myocardial infarction was 1.18(95%CI,1.08 to 1.30). Increase in CES-D score was an independent predictor in both placebo and active drug groups, and it was strongest as a risk factor for stroke among women (RR,1.29;95%CI,1.07 to 1.34). Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended.


"#I-Am-Engaged": Conceptualization and First Implementation of a Multi-Actor Participatory, Co-designed Social Media Campaign to Raise Italians Citizens' Engagement in Preventing the Spread of COVID-19 Virus.
The COVID-19 pandemic forced health authorities around the world to introduce public health measures to contain the risks of contagion. This greatly impacted on citizens' quality of life, often raising concerns and reactance. There is an ongoing urgent need to promote and sustain behavioral changes and adherence to preventive measures. Based on the theoretical framework of the Patient Health Engagement Model and a participatory co-design process, a social media campaign aimed at improving citizens' health engagement toward behavioral change for preventing the spread of COVID-19 was promoted in Italy in the early months of the pandemic. In this paper, we describe the methodological process adopted to develop the campaign, its characteristics, and the first results-in terms of audience reach and engagement in its early implementation. The discussion of this grounded-up and citizen-centered approach to social campaign development highlights key ways of promoting learning, engaging citizens, and supporting their participation in the co-production of educational interventions for behavioral change toward preventive actions.


Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.
To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function.


Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus.
The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.


Quantitative Morphological Variation in the Developing Drosophila Wing.
Quantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, Drosophila melanogaster We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental stages were studied: late larval third instar, post-pupariation and in the adult fly. We studied wild-type animals in addition to mutants of two genes (shf and ds) that have known effects on adult wing shape and size. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. In addition we provide linear rules allowing us to link wing morphology in the larva, with wing morphology in the pupa. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.


Rapid increase in breast magnetic resonance imaging use: trends from 2000 to 2011.
Breast magnetic resonance imaging (MRI) is highly sensitive for detecting breast cancer. Low specificity, cost, and little evidence regarding mortality benefits, however, limit recommendations for its use to high-risk women. How breast MRI is actually used in community settings is unknown. To describe breast MRI trends and indications in a community setting. Retrospective cohort study at a not-for-profit health plan and multispecialty group medical practice in New England of 10,518 women aged 20 years and older enrolled in the health plan for at least 1 year who had at least 1 breast MRI between January 1, 2000, and December 31, 2011. Breast MRI counts were obtained from claims data. Clinical indication (screening, diagnostic evaluation, staging or treatment, or surveillance) was determined using a prediction model developed from electronic medical records on a subset of participants. Breast cancer risk status was assessed using claims data and, for the subset, also through electronic medical record review. RESULTS; Breast MRI use increased more than 20-fold from 6.5 per 10,000 women in 2000 to 130.7 per 10,000 in 2009. Use then declined and stabilized to 104.8 per 10,000 by 2011. Screening and surveillance, rare indications in 2000, together accounted for 57.6% of MRI use by 2011; 30.1% had a claims-documented personal history and 51.7% a family history of breast cancer, whereas 3.5% of women had a documented genetic mutation. In the subset of women with electronic medical records who received screening or surveillance MRIs, only 21.0% had evidence of meeting American Cancer Society (ACS) criteria for breast MRI. Conversely, only 48.4% of women with documented deleterious genetic mutations received breast MRI screening. Breast MRI use increased steeply over 10 years and then stabilized, especially for screening and surveillance among women with family or personal history of breast cancer; most women receiving screening and surveillance breast MRIs lacked documented evidence of meeting ACS criteria, and many women with mutations were not screened. Efforts are needed to ensure that breast MRI use and documentation are focused on those women who will benefit most.


Printable logic circuits comprising self-assembled protein complexes.
This paper describes the fabrication of digital logic circuits comprising resistors and diodes made from protein complexes and wired together using printed liquid metal electrodes. These resistors and diodes exhibit temperature-independent charge-transport over a distance of approximately 10 nm and require no encapsulation or special handling. The function of the protein complexes is determined entirely by self-assembly. When induced to self-assembly into anisotropic monolayers, the collective action of the aligned dipole moments increases the electrical conductivity of the ensemble in one direction and decreases it in the other. When induced to self-assemble into isotropic monolayers, the dipole moments are randomized and the electrical conductivity is approximately equal in both directions. We demonstrate the robustness and utility of these all-protein logic circuits by constructing pulse modulators based on AND and OR logic gates that function nearly identically to simulated circuits. These results show that digital circuits with useful functionality can be derived from readily obtainable biomolecules using simple, straightforward fabrication techniques that exploit molecular self-assembly, realizing one of the primary goals of molecular electronics.


Quantitative trait loci associated with longevity of lettuce seeds under conventional and controlled deterioration storage conditions.
Lettuce (Lactuca sativa L.) seeds have poor shelf life and exhibit thermoinhibition (fail to germinate) above ∼25°C. Seed priming (controlled hydration followed by drying) alleviates thermoinhibition by increasing the maximum germination temperature, but reduces lettuce seed longevity. Controlled deterioration (CD) or accelerated ageing storage conditions (i.e. elevated temperature and relative humidity) are used to study seed longevity and to predict potential seed lifetimes under conventional storage conditions. Seeds produced in 2002 and 2006 of a recombinant inbred line (RIL) population derived from a cross between L. sativa cv. Salinas×L. serriola accession UC96US23 were utilized to identify quantitative trait loci (QTLs) associated with seed longevity under CD and conventional storage conditions. Multiple longevity-associated QTLs were identified under both conventional and CD storage conditions for control (non-primed) and primed seeds. However, seed longevity was poorly correlated between the two storage conditions, suggesting that deterioration processes under CD conditions are not predictive of ageing in conventional storage conditions. Additionally, the same QTLs were not identified when RIL populations were grown in different years, indicating that lettuce seed longevity is strongly affected by production environment. Nonetheless, a major QTL on chromosome 4 [Seed longevity 4.1 (Slg4.1)] was responsible for almost 23% of the phenotypic variation in viability of the conventionally stored control seeds of the 2006 RIL population, with improved longevity conferred by the Salinas allele. QTL analyses may enable identification of mechanisms responsible for the sensitivity of primed seeds to CD conditions and breeding for improved seed longevity.


Risk factors affecting the occurrence of acute otitis media among 2-3-year-old urban children.
The factors affecting the occurrence and recurrence of acute otitis media (AOM) were studied among 471 2-3-year-old children in two cities in Finland. Of these children, 188 had experienced greater than or equal to 3 attacks of AOM, 76 had had 1-2 attacks and 207 no otitis attacks (= control group). The study showed that the risk of recurrent AOM was increased among those children attending day-care nurseries as well as among those who had several siblings. Proneness to rhinorrhea and exposure to passive smoking at home was associated with an increased risk of AOM, while prolonged breast-feeding (greater than 6 months) seemed to reduce it. No correlation was found between the risk of recurrent AOM and the place of residence or type of housing, the parental otitis history, or atopic diathesis of a child. Thus the study suggested that to protect a young child from AOM we should promote breast-feeding and home-care for babies as well as avoid smoking in the home.


Hemimegalencephaly and focal megalencephaly in tuberous sclerosis complex.
We describe two children with complex cortical malformations as well as the typical intracranial manifestations of tuberous sclerosis complex. One child had hemimegalencephaly and the other had extensive focal megalencephaly. These cases are discussed in terms of the current concepts of cortical malformations.


Lutzomyia longipalpis (Diptera: Psychodidae) Argentina-Bolivia border: new report and genetic diversity.
American visceral leishmaniasis (AVL) has two main scenarios of transmission as follows: scattered cases in rural areas and urban outbreaks. Urban AVL is in active dispersion from the northeastern border of Argentina-Paraguay-Brazil to the South. The presence of Lutzomyia longipalpis was initially reported in urban environments in the northwestern border of the country. The presence of Lu. longipalpis, environmental variables associated with its distribution, and its genetic diversity were assessed in Salvador Mazza, Argentina, on the border with Bolivia. The genetic analysis showed high haplotype diversity, low nucleotide diversity, and low nucleotide polymorphism index. We discuss the hypothesis of an expanding urban population with introgressive hybridisation of older haplogroups found in their path in natural forest or rural environments, acquiring a new adaptability to urban environments, and the possibility of changes in vector capacity.


Systemic health status and self-reported periodontal health among South Africans.
This study sought to determine the association between systemic health and self-reported poor periodontal health in South Africa. This secondary data analysis focused on dentate adults aged >15 years (n=6,319) who participated in the South African Demographic and Health Survey (SADHS) during 2003/2004.Information obtained included socio-demographic data, and data on health risk behaviours (tobacco and alcohol use) and chronic diseases. The main outcome measure is self-reported poor periodontal health (defined as having had pain or problems with the gums in the 6 months prior to the survey date). Data analysis included t-test, chi-square and multiple logistic regression analysis. Of the respondents, 4.6% (95% CI = 3.9-5.5) self-reported having had a 'gum problem' or poor periodontal health. Those who reported poor periodontal health were significantly older than those who did not report poor periodontal health (36.2 yrs vs. 38.8 yrs; p = 0.02). In a multi-variable adjusted model, those categorized as problem drinkers (2.53; 95% CI = 1.68 - 3.82) as compared to non-drinkers, those who had suffered a stroke (4.13; 95% CI = 1.53- 11.11), or who suffered from arthritis (1.70; 95% CI = 1.00-2.90) all demonstrated significantly higher odds of reporting poor periodontal health. When compared to white South Africans, black South Africans had the highest odds of reporting poor periodontal health (3.91; 95% CI =1.38 -11.05). There is a significant association between chronic systemic conditions such as having had a stroke or suffering from arthritis and poor periodontal health in South Africa.


BDNF genotype modulates resting functional connectivity in children.
A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.


Plasma-based biomaterials for the treatment of cutaneous radiation injury.
Cutaneous wounds caused by an exposure to high doses of ionizing radiation remain a therapeutic challenge. While new experimental strategies for treatment are being developed, there are currently no off-the-shelf therapies for the treatment of cutaneous radiation injury that have been proven to promote repair of the damaged tissues. Plasma-based biomaterials are biologically active biomaterials made from platelet enriched plasma, which can be made into both solid and semi-solid forms, are inexpensive, and are available as off-the-shelf, nonrefrigerated products. In this study, the use of plasma-based biomaterials for the mitigation of acute and late toxicity for cutaneous radiation injury was investigated using a mouse model. A 2-cm diameter circle of the dorsal skin was irradiated with a single dose of 35 Gy followed by topical treatment with plasma-based biomaterial or vehicle once daily for 5 weeks postirradiation. Weekly imaging demonstrated more complete wound resolution in the plasma-based biomaterial vs. vehicle group which became statistically significant (p < 0.05) at weeks 12, 13, and 14 postmaximum wound area. Despite more complete wound healing, at 9 and 17 weeks postirradiation, there was no statistically significant difference in collagen deposition or skin thickness between the plasma-based biomaterial and vehicle groups based on Masson trichrome staining nor was there a statistically significant difference in inflammatory or fibrosis-related gene expression between the groups. Although significant improvement was not observed for late toxicity, plasma-based biomaterials were effective at promoting wound closure, thus helping to mitigate acute toxicity.


Prolonged ventilator dependence: perspective of the chronic obstructive pulmonary disease patient.
The purpose of this qualitative inquiry was to examine the meaning of prolonged mechanical ventilation from the perspective of the patient with a diagnosis of chronic obstructive pulmonary disease (COPD). Interviews were conducted with four individuals with a diagnosis of COPD who had experienced long-term ventilator dependence. Participants were asked to reflect on their experiences while they were ventilator dependent, and their narratives were utilized as text for hermeneutical analysis. The study's findings describe three distinct phases experienced by the participants, beginning with intubation and lasting until well after discharge from the hospital. The support of nurses was an important aspect of maintaining hope for the participants. The study revealed that prolonged mechanical ventilation had a profound impact on COPD patients and their sense of self. Postdischarge psychological support and follow-up with survivors of this experience is warranted.


Magnesiothermic Reduction of Silica: A Machine Learning Study.
Fundamental studies have been carried out experimentally and theoretically on the magnesiothermic reduction of silica with different Mg/SiO2 molar ratios (1-4) in the temperature range of 1073 to 1373 K with different reaction times (10-240 min). Due to the kinetic barriers occurring in metallothermic reductions, the equilibrium relations calculated by the well-known thermochemical software FactSage (version 8.2) and its databanks are not adequate to describe the experimental observations. The unreacted silica core encapsulated by the reduction products can be found in some parts of laboratory samples. However, other parts of samples show that the metallothermic reduction disappears almost completely. Some quartz particles are broken into fine pieces and form many tiny cracks. Magnesium reactants are able to infiltrate the core of silica particles via tiny fracture pathways, thereby enabling the reaction to occur almost completely. The traditional unreacted core model is thus inadequate to represent such complicated reaction schemes. In the present work, an attempt is made to apply a machine learning approach using hybrid datasets in order to describe complex magnesiothermic reductions. In addition to the experimental laboratory data, equilibrium relations calculated by the thermochemical database are also introduced as boundary conditions for the magnesiothermic reductions, assuming a sufficiently long reaction time. The physics-informed Gaussian process machine (GPM) is then developed and used to describe hybrid data, given its advantages when describing small datasets. A composite kernel for the GPM is specifically developed to mitigate the overfitting problems commonly encountered when using generic kernels. Training the physics-informed Gaussian process machine (GPM) with the hybrid dataset results in a regression score of 0.9665. The trained GPM is thus used to predict the effects of Mg-SiO2 mixtures, temperatures, and reaction times on the products of a magnesiothermic reduction, that have not been covered by experiments. Additional experimental validation indicates that the GPM works well for the interpolates of the observations.


Clinical features of familial Mediterranean fever: an Italian overview.
Familial Mediterranean Fever (FMF) is the most frequent periodic febrile syndrome among the autoinflammatory syndromes (AS), nowadays considered as innate immunity disorders, characterized by absence of autoantibodies and autoreactive T lymphocytes. FMF is a hereditary autosomal recessive disorder, characterized by recurrent, self-limiting episodes of short duration (mean 24e72 h) of fever and serositis. In FMF, periodic attacks show inter- and intra-individual variability in terms of frequency and severity. Usually, they are triggered by apparently innocuous stimuli and may be preceded by a prodromal period. The Mediterranean FeVer gene (MEFV) responsible gene maps on chromosome 16 (16p13) encoding the Pyrine/Marenostrin protein. The precise pathologic mechanism is still to be definitively elucidated; however a new macromolecular complex, called inflammasome, seems to play a major role in the control of inflammation and it might be involved in the pathogenesis of FMF. The most severe long-term complication is type AA amyloidosis, causing chronic renal failure. Two types of risk factors, genetic and non-genetic, have been identified for this complication. Currently, the only effective treatment of FMF is the colchicine. New drugs in a few colchicine resistant patients are under evaluation


Phonological memory in sign language relies on the visuomotor neural system outside the left hemisphere language network.
Sign language is an essential medium for everyday social interaction for deaf people and plays a critical role in verbal learning. In particular, language development in those people should heavily rely on the verbal short-term memory (STM) via sign language. Most previous studies compared neural activations during signed language processing in deaf signers and those during spoken language processing in hearing speakers. For sign language users, it thus remains unclear how visuospatial inputs are converted into the verbal STM operating in the left-hemisphere language network. Using functional magnetic resonance imaging, the present study investigated neural activation while bilinguals of spoken and signed language were engaged in a sequence memory span task. On each trial, participants viewed a nonsense syllable sequence presented either as written letters or as fingerspelling (4-7 syllables in length) and then held the syllable sequence for 12 s. Behavioral analysis revealed that participants relied on phonological memory while holding verbal information regardless of the type of input modality. At the neural level, this maintenance stage broadly activated the left-hemisphere language network, including the inferior frontal gyrus, supplementary motor area, superior temporal gyrus and inferior parietal lobule, for both letter and fingerspelling conditions. Interestingly, while most participants reported that they relied on phonological memory during maintenance, direct comparisons between letters and fingers revealed strikingly different patterns of neural activation during the same period. Namely, the effortful maintenance of fingerspelling inputs relative to letter inputs activated the left superior parietal lobule and dorsal premotor area, i.e., brain regions known to play a role in visuomotor analysis of hand/arm movements. These findings suggest that the dorsal visuomotor neural system subserves verbal learning via sign language by relaying gestural inputs to the classical left-hemisphere language network.


The effect of palatability of protein source on dietary selection in dairy calves.
Evidence has shown that soybean meal is perceived as more palatable than canola meal by dairy calves in short-term preference tests. This study evaluated the effect of protein source on longer-term dietary selection of dairy calves. In experiment 1, 40 Holstein bull calves (11.4 ± 4.3 d of age) were randomly assigned to 1 of 2 choice diets for 6 wk: base starter pellet (S; 12% crude protein; CP) and high-protein pellet (40% CP) containing either (1) soybean meal (SB) or (2) canola meal (CM). In wk 7 to 8, all calves were offered a single pelleted diet containing the protein source to which they were previously exposed. In experiment 2, 22 Holstein bull calves (9.9 ± 4.6d of age) were offered, for 6 wk, a choice of 2 mixed pelleted diets: (1) 70% S and 30% SB (SB mix), or (2) 70% S and 30% CM (CM mix). In wk 7 to 8, calves were randomly assigned to 1 of 2 choice diets, as in experiment 1: (1) SB + S, or (2) CM + S. All feeds were provided ad libitum. Calves received 6 L/d of milk replacer [0.75 kg/d of dry matter (DM)] for the duration of both experiments. Feed intake was recorded daily and calves were weighed every 14 d. Feeds were sampled weekly to analyze DM and nutrient intake. Mixed diets in experiment 2 were analyzed for CP in wk 4 and 6 to assess feed sorting (calculated as actual CP intake as a percentage of predicted intake). In experiment 1, calves offered SB + S in wk 1 to 6 consumed more high-protein pellet than calves offered CM + S [73 vs. 42% of DM intake (DMI)] and, consequently, more CP (168 vs. 117 g/d). Solid feed DMI and average daily gain were similar between treatments. When offered a single diet in wk 7 to 8, calves offered starter containing soybean meal increased intake to a greater extent than calves offered the starter containing canola meal. In experiment 2, calves preferred the SB mix to CM mix (preference ratio: 0.7). Calves consumed more CP than predicted from SB mix in wk 4 and 6 (108 ± 2.0%), indicating that they were sorting in favor of SB. In contrast, calves consumed less CP than predicted from CM mix in wk 4 (81.48 ± 4.1%), indicating that they were sorting against CM. When assigned to choice treatments in wk 7 to 8 of experiment 2, calves offered SB + S consumed more protein pellet than calves offered CM + S (81 vs. 31% DMI) and consumed more CP (378 vs. 196 g/d). Average daily gain was greater for calves offered SB + S but DMI was similar. Overall, these results suggest that dietary selection was influenced by innate feed preferences, and milk-fed calves may not be sensitive to protein imbalances in their diet.


Inappropriate Preoperative Gabapentinoid Use Among Patients With Carpal Tunnel Syndrome.
Gabapentinoids are commonly prescribed for the treatment of neuropathic pain but are not recommended for the primary treatment of carpal tunnel syndrome (CTS). We sought (1) to investigate the preoperative use of gabapentinoids for the treatment of CTS and (2) to determine whether preoperative exposure is associated with persistent gabapentinoid and opioid use after carpal tunnel release. We performed a retrospective cohort study using IBM MarketScan Research Databases (2010-2017) of patients who did not fill a gabapentinoid or opioid prescription within 3 months of a new CTS diagnosis undergoing surgical release. Our primary outcomes included preoperative gabapentinoid prescription fills associated with CTS and persistent prescription fills of gabapentinoids and opioids at 91 to 180 days after surgery. Multivariable logistic regression models were used to evaluate the association between patient-level factors and persistent gabapentinoid and opioid use. Of the 56,593 patients without a previous gabapentinoid or opioid prescription prior to diagnosis of CTS, 3,474 patients (6%) filled a gabapentinoid prescription before carpal tunnel release. Overall, 835 patients (24% of the preoperative users) continued to fill gabapentinoid prescriptions at 91 to 180 days after surgery. Of the preoperative gabapentinoid users, 20% (702 patients) continued to fill opioid prescriptions at 91 to 80 days after release. After adjusting for patient characteristics, preoperative gabapentinoid use was associated with increased odds of persistent postoperative gabapentinoid use (preoperative gabapentinoid, 22% adjusted probability; 95% confidence interval [95% CI], 20.3%-23.0%, no preoperative gabapentinoid use, 1%; 95% CI, 1.2%-1.4%) and persistent postoperative opioid use (preoperative gabapentinoid, 18% adjusted probability; 95% CI, 17%-20%), no preoperative gabapentinoid, 9%; 95% CI, 8.6%-9.1%). Despite a lack of evidence to support the use of gabapentinoids for CTS, 6% of patients are prescribed a gabapentinoid prior to surgery, and prolonged use is common. Given the effectiveness of surgical release and the risks associated with gabapentinoids, greater attention is needed to ensure that gabapentinoids are prescribed appropriately, avoided when possible, and stopped after surgery. Prognostic II.


Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat.
To determine whether VIP functions as a physiological PRL-releasing factor, the effects of immunoneutralization of endogenous vasoactive intestinal peptide (VIP) on the PRL secretory response to suckling and ether stress were assessed. Using a porcine VIP-thyroglobulin conjugate as antigen, a peptide-specific antiserum was generated in a rabbit which bound porcine VIP with a Kd of 5.1 X 10(-11) M and a maximum binding capacity of 1830 ng/ml. In a RIA, this antiserum demonstrated immunoreactive VIP in tissue extracts of various regions of the brain and gastrointestinal tract. IR VIP in extracts of cerebral cortex and hypothalamus coeluted with synthetic porcine VIP on Bio-Gel P-30 column chromatography. Using chronically implanted right atrial catheters for blood sampling to avoid effects of stress and anesthesia, PRL blood levels in normal controls began to rise almost immediately after initiation of suckling from basal values of 3.0 +/- 0.9 ng/ml to reach a plateau of 158.1 +/- 33.5 ng/ml after 40 min. When the VIP antiserum was administered immediately before initiation of suckling, the onset of the PRL response was delayed by 40 min, but PRL levels then rose at a slower rate to reach the plateau level of normal animals approximately 80 min later. When VIP antiserum was administered to rats who had been suckling for at least 1 h, PRL levels fell from a mean basal elevated level of 152.7 +/- 16.0 ng/ml to a nadir of 50.4 +/- 9.1 ng/ml 80 min after injection and then gradually returned to basal levels. The effect of VIP antiserum was studied in rats in whom PRL secretion was increased by exposure to ether, a stimulus that acts on the release phase of PRL secretion. In rats in whom the depletion-transformation of PRL was induced by a prior brief period of suckling, subsequent exposure to ether caused a rise in serum PRL levels. The response was completely blocked in rats given VIP antiserum, whereas animals given nonimmune serum showed a significant increase in serum PRL to 38.6 +/- 17.3 ng/ml. We conclude from these studies that VIP mediates the acute PRL response to suckling and is required for maintenance of PRL levels in continuously suckling animals but is not the only factor causing PRL elevation. Complete abolition by the VIP antiserum of the PRL response to ether indicates that the effect of the anesthetic is mediated entirely by the release of VIP. These findings are consistent with the view that VIP is a physiological PRL-releasing factor in the rat.


Attitudes toward victims of rape: effects of gender, race, religion, and social class.
Although previous literature focusing on perceptions of victims of rape has examined how gender, race, and culture influence the attitudes one holds toward victims, these studies have yielded mixed results. This study compared perceptions of victims of rape across a wide range of ages, educational backgrounds, religions, and income levels, while focusing on gender and racial differences. Results indicate (N = 220) that victims of rape are generally viewed more sympathetically by females than by males and by Whites than by African Americans. However, the effect of race disappears when socioeconomic variables are controlled, suggesting a more complex relationship. Also, a hierarchical regression indicates that age, sex, education, and income are significant predictors of attitudes toward victims. This study builds on existing research that examines such attitudes from a cultural perspective and extends this literature by examining the interactive effects of several demographic variables within a community sample.


A micro credential for interoperability.
In the midst of a global pandemic the need for health and social care providers to commit to, and deliver on, integrated patient-centered care services has been accelerated. Globally, health and social care programme administrators are turning to digital devices and applications to provide supporting infrastructure which can offer safe access to health information at the point of care. Digitalisation is increasingly considered a key requirement to support diagnostics and therapeutic care services in health care delivery. The open source community are responding to this need to advance integrated care and digital services by providing targeted resources to address the interoperability challenge. Addressing interoperability in health systems is a core part of achieving sustainable enterprise wide integrated care. Using Open Innovation 2.0 methods for advancing knowledge on interoperability, this paper describes the development of a micro credential for knowledge transfer on interoperability created by the Centre for eIntegrated Care (CeIC). Designed and developed to signpost interested stakeholders to targeted material and build understanding and capacity on the topic. The design approach and initial resource content are explained through the lens of a specific research project funded by an Elite S Fellowship to advance leadership and standardisation for Information and Communications Technology (ICT) in Europe.


The miRNA-24, miRNA-21 expressions and matrix metalloproteinase-7 level in exhaled breath condensate of children with primary spontaneous pneumothorax.
Bullous lung diseases may cause primary spontaneous pneumothorax (PSP) in children. The microRNAs (miRNAs) are non-coding RNAs that participate in regulation of inflammation and cancer. We hypothesized that children with bullous lung disease and PSP may have altered miRNA expressions in their exhaled breath condensates (EBCs). Therefore, a prospective study was performed to evaluate the miRNA-24 and 21 expression, and the matrix metalloproteinase-7 (MMP-7) levels in EBC of children with PSP. Children with PSP were evaluated for age, gender, clinical features and results of surgical treatment. EBC samples (500-1000 ml) were collected to evaluate the miRNA-21, 24 expressions, and MMP-7, and tissue-inhibitor-MMP-1 (TIMP-1) levels. miRNA expressions and MMP levels of patients were compared with healthy controls (control group (CG),n= 12). Subjects (n= 16) with a mean age of 15 years (10-19 years), and a male-to-female ratio of 14:2 were enrolled in this study. The most common presenting symptom was sudden chest pain (n= 14). In 62.5% of the cases an underlying bullous lung disease were detected. During an average of 16.6 months (1-60 months) follow up period, four subjects relapsed. The mean MMP-7 (1.74-1.57 ng ml-1), and TIMP-1 (1.92-1.84 ng ml-1) levels were similar between both groups (p> 0.05). miRNA-24 expression was significantly decreased in the PSP group, when compared to the CG (0.16-1 2-ΔΔCT,p< 0.05). In addition, the miRNA-21 expression was not different between the two groups (p> 0.05). In conclusion, the miRNA-24 levels were significantly decreased in children with PSP. Taken together, children with PSP, especially those with bullous disease, should be closely monitored in the long-term period.


Finding critical exponents for two-dimensional Hamiltonian maps.
The transition from integrability to nonintegrability for a set of two-dimensional Hamiltonian mappings exhibiting mixed phase space is considered. The phase space of such mappings show a large chaotic sea surrounding Kolmogorov-Arnold-Moser islands and limited by a set of invariant tori. The description of the phase transition is made by the use of scaling functions for average quantities of the mapping averaged along the chaotic sea. The critical exponents are obtained via extensive numerical simulations. Given the mappings considered are parametrized by an exponent gamma in one of the dynamical variables, the critical exponents that characterize the scaling functions are obtained for many different values of gamma . Therefore classes of universality are defined.


Magnetic relaxation in cobalt(ii)-based single-ion magnets influenced by distortion of the pseudotetrahedral [N2O2] coordination environment.
The synthesis, structure, and magnetic properties of two mononuclear cobalt(ii) complexes [Co(LSal,2-Ph)2] (1) and [Co(LNph,2-Ph)2] (2) are reported. The utilized sterically demanding Schiff-base ligands HLSal,2-Ph (2-(([1,1'-biphenyl]-2-ylimino)methyl)phenol) and HLNph,2-Ph (1-(([1,1'-biphenyl]-2-ylimino)methyl)naphthalen-2-ol) lead to a strong distortion of the [N2O2] coordination environment in the complexes 1 and 2, which can be primarily attributed to the variation in the dihedral angle between the planes of the two chelate ligands. Magnetic susceptibility and FD-FT THz-EPR measurements as well as ab initio calculations reveal that both complexes exhibit an easy-axis type of anisotropy. For both compounds frequency-dependent ac susceptibility measurements show an out-of-phase susceptibility under applied static fields of 400 and 1000 Oe. A detailed analysis of the underlying relaxation process is given, revealing significant differences in the contributions of Orbach, Raman, and direct processes within the observed temperature range. Fitting of the magnetic data leads to a spin-reversal barrier of 49 cm-1 for 1 at an applied field of 1000 Oe. For 2 the barrier is not well defined by the analysis of the relaxation times and is, therefore, approximated by the experimental barrier derived from FD-FT THz-EPR measurements (62.8 cm-1). The results from ab initio calculations and FD-FT THz-EPR measurements show that the distortion of the coordination sphere in complexes 1 and 2 from the pseudotetrahedral towards a square-planar coordination geometry leads to an increase in both the axial (D) and the rhombic zero-field splitting (E).


Pre-existing histological type and developmental mechanism of mucinous noncystic carcinoma of pancreas.
Eleven cases with mucinous noncystic carcinoma (MC) of the pancreas were studied by histology and mucin immunohistochemistry, to elucidate the mechanism, or route of development, and pre-existing histological type of MC of the pancreas. These MCs were observed in close approximation to, or surrounding, intraductal papillary-mucinous carcinomas (IPMCs), and were centrally situated among ductal adenocarcinomas (DAs). Hence, the 11 cases originated from 8 IPMCs and 3 DAs. The mechanism and routes to MC were divided into four types as follows: IPMC directly invaded the stroma (4 cases), over-production of mucin in IPMC expanded the branches of the pancreatic duct possibly resulting in rupture (3 cases), DA underwent extreme mucinous degeneration (3 cases), and a recurrent form, as MC, at the surgical stump of IPMC (one case). The outcomes of MC cases with IPMC had variable survival rates, while those from DA had short durations. MUC immunoreactivity in MC was divided into three categories; anti-MUC1-positive only (2 IPMCs, 2 DAs), mixed anti-MUC1 and anti-MUC2-positive (3 IPMCs, one DA) and anti-MUC-positive only (3 IPMCs). Pre-existing MC histological types included both IPMC and DA. These two pre-existing types of MC involved mucin overproduction and mucinous degeneration. MUC immunoreactivity in MC revealed three patterns, which may be related to variable outcomes.


Auditory temporal processing deficits in children with reading disabilities.
The role of central auditory processing in reading skill development and reading disorders is unclear. The purpose of this study was to examine whether individuals with specific reading disabilities (SRD) have deficits in processing rapidly presented, serially ordered non-speech auditory signals. To this end, we compared 12 children with SRD and 12 children without SRD on their ability to detect differences and similarities in pure tones of 1000 and 2000 Hz when these signals were presented in pairs (same or different tones, randomly ordered) with short (50 ms) versus long (500 ms) inter-stimulus intervals (ISI). Results showed that the children with SRD had significant difficulty in discriminating between pure tones with short, but not long ISI, whereas the controls performed well with both short and long ISI. The two groups did not differ significantly on measures of attention (d2) and performance IQ, and there were no significant correlations between these measures and ISI performance. There were significant correlations between the short ISI performance and phonologic awareness test results when the two groups were combined. These findings support the specific rapid auditory processing deficit hypothesis of SRD. Examination of intra-subject variability in performance indicated that children from the SRD group showed both decrement in performance with time on task and high overall variability in performance as compared to the controls. These findings underpin the importance of using time-series analyses of performance.


Mapping the SRS-22r questionnaire onto the EQ-5D-5L utility score in patients with adolescent idiopathic scoliosis.
This is a prospective study to establish prediction models that map the refined Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ-5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients. Comparison of treatment outcomes in AIS can be determined by cost-utility analysis. However, the mainstay spine-specific health-related quality of life outcome measure, the SRS-22r questionnaire does not provide utility assessment. In this study, AIS patients were prospectively recruited to complete both the EQ-5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares regression was undertaken to develop mapping models, which the validity and robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D-5L utility scores were regressed on demographics, Cobb angle, curve types, treatment modalities, and five domains of the SRS-22r questionnaire. Three models were developed using stepwise selection method. EQ-5D-5L scores were regressed on 1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and interaction terms, and 3) as per 2 plus demographic and clinical characteristics. Model goodness-of-fit was assessed using R-square, adjusted R-square, and information criteria; whereas the predictive performance was evaluated using root mean square error (RMSE), mean absolute error (MAE), and the proportion of absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and 'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%). Three models demonstrated an acceptance predictive performance in error analysis applying 10-fold cross-validation to three models where RMSE and MAE were between 0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore recommended out of three mapping models established in this paper. To our knowledge, this is the first study to map a spine-specific health-related quality of life measure onto EQ-5D-5L for AIS patients. With the consideration and incorporation of demographic and clinical characteristics, over 60% variance explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L utility scores from existing SRS-22r data for health economic appraisal of different treatment options.


Voice outcome in T1a midcord glottic carcinoma: laser surgery vs radiotherapy.
To compare voice quality after radiotherapy or endoscopic laser surgery in patients with similar T1a midcord glottic carcinomas according to a validated multidimensional protocol. Retrospective cohort study. University cancer referral center. Two cohorts of consecutive patients willing to participate after treatment for primary T1a midcord glottic carcinoma with laser surgery (18 of 23 eligible) or radiotherapy (16 of 18 eligible). Posttreatment voice quality was evaluated according to a multidimensional voice protocol based on validated European Laryngological Society recommendations, including perceptual, acoustic, aerodynamic, and stroboscopic analyses, together with patient self-assessment using the Voice Handicap Index. Approximately half of the patients had mild to moderate voice dysfunction in the perceptual analysis (53% [8 of 15] in the radiotherapy group and 61% [11 of 18] in the laser surgery group) and on the Voice Handicap Index (44% [7 of 16] in the radiotherapy group and 56% [10 of 18] in the laser surgery group). The voice profile in the laser surgery group was mainly breathy; in the radiotherapy group, it was equally breathy and rough, with a trend for more jitter in the acoustic analysis. There was no statistical difference in the severity of voice dysfunction between the groups in any of the variables. Endoscopic laser surgery offers overall voice quality equivalent to that of radiotherapy for patients with T1a midcord glottic carcinoma, although specific voice profiles may ultimately be different for the 2 modalities. We believe that endoscopic laser surgery is the preferred treatment in these patients because it provides oncologic control similar to that of radiotherapy and the additional benefits of lower costs, shorter treatment time, and the possibility of successive procedures.


Recurrent blooms of Heterosigma akashiwo (Raphidophyceae) in the Piraquê Channel, Rodrigo de Freitas Lagoon, southeast Brazil.
Six blooms of Heterosigma akashiwo (Raphidophyceae) were observed from March 2007 through March 2008 in the Rodrigo de Freitas Lagoon, a semi-confined eutrophic system located in Rio de Janeiro state, southeast Brazil. Vegetative cells of H. akashiwo analysed by optical and electron microscopy showed morphology as described in the literature. The blooms (2.8 × 10(4) to 4 × 10(8) cell.L(-1)) were restricted to the middle section of the Piraquê Channel, which is situated in the northeastern part of the lagoon and receives freshwater inflow. The salinity of subsurface water and the channel depth showed significant negative correlations with H. akashiwo abundances, and appeared to restrict the blooms to this compartment of the lagoon. No fish mortality was associated with the H. akashiwo blooms, nor were brevetoxins detected in a cell extract obtained from the bloom observed on 19 March 2007.


Efficient recovery of proteins from multiple source samples after TRIzol(®) or TRIzol(®)LS RNA extraction and long-term storage.
Simultaneous isolation of nucleic acids and proteins from a single biological sample facilitates meaningful data interpretation and reduces time, cost and sampling errors. This is particularly relevant for rare human and animal specimens, often scarce, and/or irreplaceable. TRIzol(®) and TRIzol(®)LS are suitable for simultaneous isolation of RNA, DNA and proteins from the same biological sample. These reagents are widely used for RNA and/or DNA isolation, while reports on their use for protein extraction are limited, attributable to technical difficulties in protein solubilisation. TRIzol(®)LS was used for RNA isolation from 284 human colon cancer samples, including normal colon mucosa, tubulovillous adenomas, and colon carcinomas with proficient and deficient mismatch repair system. TRIzol(®) was used for RNA isolation from human colon cancer cells, from brains of transgenic Alzheimer's disease mice model, and from cultured mouse cortical neurons. Following RNA extraction, the TRIzol(®)-chloroform fractions from human colon cancer samples and from mouse hippocampus and frontal cortex were stored for 2 years and 3 months, respectively, at -80°C until used for protein isolation.Simple modifications to the TRIzol(®) manufacturer's protocol, including Urea:SDS solubilization and sonication, allowed improved protein recovery yield compared to the TRIzol(®) manufacturer's protocol. Following SDS-PAGE and Ponceau and Coomassie staining, recovered proteins displayed wide molecular weight range and staining pattern comparable to those obtainable with commonly used protein extraction protocols. We also show that nuclear and cytosolic proteins can be easily extracted and detected by immunoblotting, and that posttranslational modifications, such as protein phosphorylation, are detectable in proteins recovered from TRIzol(®)-chloroform fractions stored for up to 2 years at -80°C. We provide a novel approach to improve protein recovery from samples processed for nucleic acid extraction with TRIzol(®) and TRIzol(®)LS compared to the manufacturer`s protocol, allowing downstream immunoblotting and evaluation of steady-state relative protein expression levels. The method was validated in large sets of samples from multiple sources, including human colon cancer and brains of transgenic Alzheimer's disease mice model, stored in TRIzol(®)-chloroform for up to two years. Collectively, we provide a faster and cheaper alternative to the TRIzol(®) manufacturer`s protein extraction protocol, illustrating the high relevance, and wide applicability, of the present protein isolation method for the immunoblot evaluation of steady-state relative protein expression levels in samples from multiple sources, and following prolonged storage.


EIWA-III measures of cognitive function in young Puerto Rico patients with epilepsy.
Evaluation and measurement of intelligence contributes significantly to the scientific endeavor of psychology as a science. This study was exploratory and descriptive, with twenty young patients with epilepsy from Puerto Rico of ages between 16-20 years. Compared the execution of a matched group of the normative sample and the group of adults 21 to 64 years with epilepsy belonging to the standardization sample in Puerto Rico. The data was analyzed using descriptive and inferential statistical calculations. Survey results reflect significant differences in the scores of the subtests that make up the intelligence scale EIWA-III. In all measures, the group of participants with epilepsy rate was lower than the reference group. The comparison of scores on the subtests that measure executive functions was analyzed by the working memory index (WMI). Based on the data obtained, the performance in executive functions EIWA-III is significantly lower in participants with epilepsy compared to the reference groups. Analysis of variance/ANOVA showed no significant differences between IQ scale for implementation (F = 8.77) with a probability of 0.001, CI scale (F = 4.35) was 0.01 and verbal scale IQ (F = 2.67) was 0.05 for the group of young patients from 16 to 20 years with epilepsy, their IQ score compared with the normative group on the subscales that comprise the Verbal Scale, Performance and Total rates of IQ trial EIWA-III. In light of these results, the statistically significant differences for each subscale: Verbal IQ, Performance, Total and indexes EIWA-III, suggest that the level of intelligence of sample group, 16 to 20 years old with epilepsy, was below average in comparison with the normative group. The results are consistent with the literature on cognitive neuropsychology and performance of subjects with epileptic diseases.


Three different endogenous alpha-L-fucosyltransferases expressed in COS cells.
The monkey kidney COS cell line is frequently used for the transient expression of cloned human fucosyltransferase cDNAs in the belief that negligible endogenous expression of fucosyltransferase genes occurs in these cells. In the course of transfection experiments we observed weak cell surface expression of sialyl-Lex and weak fucosyltransferase activity in extracts of control untransfected cells. Since these activities could complicate interpretation of the results with the transfected genes, a more detailed examination was undertaken that has now revealed expression of three different fucosyltransferases in the cells. One enzyme, which utilises N-acetyllactosamine as substrate, has a pH optimum of 7.0, is resistant to heat inactivation, and has been tentatively identified as an alpha1,3-fucosyltransferase. A second enzyme which acts on asialo-fetuin has a pH optimum of 5.5 and is rapidly inactivated by heat; the acceptor sugar and positional linkage of the transferred fucose are not yet established. A third enzyme that utilises asialo-agalacto-fetuin as acceptor is provisionally identified as an alpha1,6-fucosyltransferase.


Specific reactions and cross reactions of anti-penicilloyl antibodies.
In human sera the specific reactions and cross reactions of antibodies directed against the penicilloyl groups were determined using different penicilloyl derivatives as antigen. The penicilloyl group providing the highest titre in one Ig class was said to define the specific reaction for this Ig class. This criterium was justified by the fact that antibodies evoked by long-term treatment with benzylpenicillin showed specific reaction to the benzylpenicilloyl group. Moreover, specific reactions of antibodies of different Ig classes in one serum were the same. Both the side chain and the thiazolidine ring of the penicilloyl group can serve as antigenic determinants.


A reference model approach to stability analysis of neural networks.
In this paper, a novel methodology called a reference model approach to stability analysis of neural networks is proposed. The core of the new approach is to study a neural network model with reference to other related models, so that different modeling approaches can be combinatively used and powerfully cross-fertilized. Focused on two representative neural network modeling approaches (the neuron state modeling approach and the local field modeling approach), we establish a rigorous theoretical basis on the feasibility and efficiency of the reference model approach. The new approach has been used to develop a series of new, generic stability theories for various neural network models. These results have been applied to several typical neural network systems including the Hopfield-type neural networks, the recurrent back-propagation neural networks, the BSB-type neural networks, the bound-constraints optimization neural networks, and the cellular neural networks. The results obtained unify, sharpen or generalize most of the existing stability assertions, and illustrate the feasibility and power of the new method.


Conditional superagonist CTL ligands for the promotion of tumor-specific CTL responses.
Although it has been demonstrated that CTLs can be raised against tumor-associated self-antigens, achieving consistent and effective clinical responses has proven challenging. Superagonist altered peptide ligands (APLs) can often elicit potent antitumor CTL responses where the native tumor-associated epitope fails. Current methods have identified a limited number of superagonist APLs, including the prototypic 27L mutant of MART-1. However, more comprehensive screening strategies would be desirable. In this study, we use a novel genetic screen, involving recombinant technology and class I Ag cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant by surveying the effectiveness of virtually every single amino acid substitution mutant of 27L to activate human Ag-specific CTL clones recognizing the wild-type MART-1(26-35) epitope. We identify three novel mutant epitopes with superagonist properties that are functionally superior to 27L; however, the ability of a given analogue to act as superagonist varies among patients and suggests that a given superagonist APL may be ideally suited to different patients. These findings endorse the use of comprehensive methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients.


Solvent Dielectricity-Modulated Helical Assembly and Morphologic Transformation of Achiral Surfactant-Inorganic Cluster Ionic Complexes.
Ionic complexes comprising single/double chain cationic surfactant and Lindqvist-type polyoxomolybdate anionic cluster were used for controlled self-assembly in organic solutions. In the solvent with low dielectric constant the complexes self-assembled into flat ribbon like lamellar aggregations with an inverse bilayer substructure where the cluster located at the middle. Under the condition of increased dielectric constant, the solvent triggered the formation of helical self-assemblies, which finally transformed from helical ribbons to the flower-like assemblies due to the bilayer becoming excessively twisted. The self-assembled morphology and the substructure were characterized by SEM, TEM, and XRD. The solvent dielectricity-controlled morphologic transformations modulated by the variation of electrostatic interactions between organic cations and inorganic polyanions were demonstrated by 1H NMR and IR spectra. The strategy in this work represents an effective route in targeting the chirality-directed functionalization of inorganic clusters by combining controllable and helical assemblies of achiral polyoxometalate complexes in one system.


Birefringent coupler for integrated optics.
An optical coupler has been developed whereby a birefringent prism or substrate is utilized to couple light into thin film optical waveguides. The coupler is designed so that the incident light, polarized as an extraordinary wave, passes through the birefringent material at such an angle that the index of refraction in the input medium is higher than that of the waveguide. In addition, the orientation of the birefringent material is chosen so that the reflected waves within the waveguide are incident on the input medium at such an angle that the medium index of refraction appears lower than that of the waveguide. In this way, the light is trapped within the waveguide and, when the light is incident at the appropriate angle, this light propagates in the waveguide as a single mode. Coupling takes place over the whole area common to the waveguide and input medium; thus, neither a sharp edge nor a trapped evanescent region are required to prevent the light coupled into the waveguide from leaking back into the coupling prism. The absence of a boundary makes it practical to couple wide beams of light into planar guides. Couplers made of calcite have been used to couple TM He-Ne laser light into multimode waveguides formed of liquids and optical cement.


Nurses experience with body care among palliative care patients: a phenomenological study.
Palliative care is defined as active and global care that provides holistic care integrating the body, mind and spirit of the dying person. A person's health deteriorates at the end of life and nurses facilitate patients to manage their personal body care. Knowing and considering the impact of disease on individuals' lives, how they adapt to cope with it, and the meaning they give to it, can help nurses. This is because of the embodiment concept of living in and through our bodies. The aim of the study is to explore palliative care patients' experiences with nurses during body care. A descriptive phenomenological approach based on Husserl's philosophical perspective was used. A purposive sample of eight palliative care patients were enrolled in the study. Semi-structured interviews were conducted between November 2018 and January 2019, in an Italian hospice. The interviews were about patients' feelings during nursing body care. The transcripts were analysed using Giorgi's phenomenological method. Several strategies were used to ensure the study's reliability. The qualitative analysis revealed six categories that converged in three themes: 1) body care requires a specific competence; 2) patients experience difficulties during care by nurses; 3) compassionate care relationships help patients to find wellbeing and balance. People at the end of life find the deterioration of their body distressing and a reminder that they are about to die. These considerations give us an understanding of patient embodiment and the significance of a patient's lived experiences at the end of their life. This phenomenon in nursing should be explored further in future research, to help inform more targeted care strategies.


What choice in infant feeding methods?
Despite concerted efforts to encourage breast-feeding, one-third of women in the UK choose to formula feed from the onset, and 75% mothers are using formula by four months. Yet these mothers are often denied information on an appropriate formula to use, how to prepare formula correctly or how to sterilise and store bottles of formula or expressed breast milk. This is partly because of a deliberate policy by some health professionals and partly because of the regulations restricting manufacturers from communicating with the public. The author argues that parents are entitled to information on all aspects of infant feeding and infant nutrition, not solely on breast-feeding. Not to provide this may mean infants are put at risk by inappropriate use of breast-milk substitutes and poor hygiene practices in preparing feeds. There should be appropriate collaboration between health professionals, health promotion specialists, Government and the formula manufacturers to ensure a more balanced and realistic approach.


Facile Synthesis of L-Cysteine Functionalized Graphene Quantum Dots as a Bioimaging and Photosensitive Agent.
Nowadays, a larger number of aggressive and corrosive chemical reagents as well as toxic solvents are used to achieve structural modification and cleaning of the final products. These lead to the production of residual, waste chemicals, which are often reactive, cancerogenic, and toxic to the environment. This study shows a new approach to the modification of graphene quantum dots (GQDs) using gamma irradiation where the usage of reagents was avoided. We achieved the incorporation of S and N atoms in the GQD structure by selecting an aqueous solution of L-cysteine as an irradiation medium. GQDs were exposed to gamma-irradiation at doses of 25, 50 and 200 kGy. After irradiation, the optical, structural, and morphological properties, as well as the possibility of their use as an agent in bioimaging and photodynamic therapy, were studied. We measured an enhanced quantum yield of photoluminescence with the highest dose of 25 kGy (21.60%). Both S- and N-functional groups were detected in all gamma-irradiated GQDs: amino, amide, thiol, and thione. Spin trap electron paramagnetic resonance showed that GQDs irradiated with 25 kGy can generate singlet oxygen upon illumination. Bioimaging on HeLa cells showed the best visibility for cells treated with GQDs irradiated with 25 kGy, while cytotoxicity was not detected after treatment of HeLa cells with gamma-irradiated GQDs.