Evaluation of Slug expression is useful for predicting lymph node metastasis and survival in patients with gastric cancer.
Slug is a transcription factor that activates the epithelial-mesenchymal transition (EMT) process in cancer progression. The aim of our study was to evaluate the clinical significance of Slug expression in gastric cancer. The expression of Slug in gastric cancer tissues of 456 patients who underwent gastrectomy was evaluated by immunohistochemistry using tissue microarrays. Slug expression level was defined by the composite score determined by multiplying the tumor staining scores for intensity and extent. The associations of Slug expression with clinicopathological characteristics and overall and recurrence-free survival were analyzed. Patients were divided into three groups according to Slug composite score (≤4, 6, and 9). Low, mid, and high expression of Slug was observed in 104 (22.7%), 130 (28.3%), and 225 (49.0%) of cases, respectively. Overall survival and recurrence-free survival progressively increased from high to low Slug expression. In terms of lymph node metastasis, the rate of positive lymph node metastasis was 38/104 (36.5%), 79/130 (60.8%), and 178/225 (79.1%) in low, mid, and high Slug expression groups, respectively, displaying a tendency to increase with higher Slug expression. In a multivariate analysis adjusting for patient age, tumor size, tumor depth, and histology, high Slug expression was associated with a high rate of positive lymph node metastasis compared with low Slug expression (odds ratio 3.42; 95% confidence interval, 1.74-6.69). In a subgroup analysis of T1 cancer, patients with negative Slug expression (defined as <5% positive tumor cells or no/weak staining) showed no lymph node metastasis (0/13), whereas those with positive Slug expression showed 15.9% (17/107) lymph node metastasis, with a negative predictive value of 100%. High expression of Slug in gastric cancer tissue was associated with lymph node metastasis and poor survival. Evaluation of Slug would be useful for discriminating patients at high risk of lymph node metastasis in early gastric cancer.


Typicality effects in face and object perception: further evidence for the attractor field model.
In a previous study, it was shown that a 50/50 morph of a typical and an atypical parent face was perceived to be more similar to the atypical parent face than to the typical parent face (Tanaka, Giles, Kremen, & Simon, 1998). Experiments 1 and 2 examine face typicality effects in a same/different discrimination task in which typical or atypical faces and their 80%, 70%, 60%, and 50% morphs were presented sequentially (Experiment 1) or simultaneously (Experiment 2). The main finding was that in both modes of presentation, atypical morphs were more poorly discriminated than their corresponding typical morphs. In Experiment 3, typicality effects were extended to the perception of nonface objects; in this instance, it was found that 50/50 morphs of birds and cars were judged to be more similar to their atypical parents than to their typical parents. These results are consistent with an attractor field model, in which it is proposed that the perception of a face or object stimulus depends not only on its fit to an underlying representation, but also on the representation's location in the similarity space.


Management of bulbar symptoms in amyotrophic lateral sclerosis.
The bulbar symptoms of ALS include difficulty with the management of swallowing, saliva, aspiration, and communication. These symptoms originate from the disability of the oropharyngeal muscles and actually represent varying degrees of severity of a single problem. The management of these symptoms requires the concerted effort of a rehabilitation team, which should include a surgeon, speech pathologist, neurologist, psychosocial worker, and dietitian. Early education of the patient and patient's family greatly facilitates successful management of bulbar symptoms. Early recognition of the signs of dysphagia, aspiration, and communicative disability are important in order to provide solutions before severe and possibly life-threatening debilitation occurs. The treatments and techniques presented in this chapter must be applied to each patient on an individual basis. The moral and social decisions regarding the providing or withholding of treatment to ALS patients are difficult ones. It is important, however, to realize that management decisions of ALS patients must deal not only with the quantity of life but also the quality of life. This distinction often falls into a 'gray zone' with management of bulbar symptoms since swallowing difficulties are life-threatening as well as uncomfortable. One of the difficulties that we present ourselves as health care providers in ALS is that, more often than not, our patient is in a noncommunicative position and cannot contribute to treatment decisions. If careful and aggressive care is taken to preserve the communicative abilities of our patients, the difficult situation of making decisions based on the family's inclinations and our own inclinations can be avoided. When we are confronted with a decision to maintain or cease support for a patient, the moral and emotional issues that present can be overwhelming. However, the patient's input, if it were direct and included the ability to express complex thoughts, could often provide the information necessary to make the decisions more clear.


Brain adenosine modulation of behavioral interactions between ethanol and carbamazepine in mice.
The effect of the anticonvulsive drug carbamazepine on ethanol-induced motor incoordination and loss-of-righting reflex was investigated in male CD-1 mice. The results of the investigation showed that carbamazepine significantly potentiated the motor incoordinating effect of ethanol in a dose-dependent fashion. Although carbamazepine did not alter the onset time, it significantly prolonged the duration of ethanol-induced loss-of-righting reflex. Pretreatment with theophylline significantly attenuated the carbamazepine-induced potentiation of ethanol-induced motor incoordination and loss-of-righting reflex. Results from a blood ethanol study indicated no effect of carbamazepine on the clearance of ethanol. The data suggest the involvement of nonadenosinergic mechanism in carbamazepine-ethanol behavioral interactions which is responsible for the accentuating effects of carbamazepine on ethanol-induced motor incoordination and duration of loss-of-righting reflex.


Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients.
We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset. VEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption. VEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis. VEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.


The role of thromboxane (TX) A2 in rabbit arterial thrombosis induced by endothelial damage.
To clarify the role of thromboxane (TX) A2 in arterial thrombus formation, we examined the antithrombotic effects of both a TXA2 synthetase inhibitor (CV-4151) and a TXA2 receptor antagonist (AA-2414) on the rabbit common carotid artery thrombosis which was induced by injury of the endothelium by treatment with 0.25% pronase solution. CV-4151 (1,10 mg/kg, p.o.) and AA-2414 (10 mg/kg, p.o.) significantly inhibited thrombus formation. Furthermore, the combined use of CV-4151 and AA-2414 (0.1 mg/kg, p.o. each) significantly inhibited thrombus formation, though these drugs at the same doses had no effect when administered singly. The plasma level of 11-dehydro TXB2 increased significantly during thrombus formation, and CV-4151 (10 mg/kg) markedly inhibited this increase. There was a significant correlation between the in vivo antithrombotic effects of these drugs and their ex vivo inhibitory effects on arachidonic acid-induced platelet aggregation. The antithrombotic effect of CV-4151 also correlated significantly with its ability to inhibit the production of serum TXA2. These results show that TXA2 may play an important role in the thrombus formation in arterial thrombosis.


Energy and fat intake in obese and lean children at varying risk of obesity.
This study compared lean children at high risk (HR) and low risk (LR) of obesity and obese children (OB) to assess the relationship between their energy (EI) and fat intake and adiposity. Cross-sectional study of energy and fat intake in children, using 7-day weighed intakes validated by doubly labelled water (DLW) energy expenditure. A total of 114 pre-pubertal children, 50 HR (mean+/-s.d., 6.7+/-0.6 y, 25.7+/-4.8 kg, 21.3+/-6.6% body fat), 50 LR (mean+/-s.d., 6.6+/-0.8 y, 23.6+/-3.7 kg, 18.9+/-5.7% body fat) and 14 OB (mean+/-s.d., 6.8+/-1.0 y, 37.7+/-5.3 kg, 34.8+/-5.6% body fat). Body fatness was measured using deuterium dilution, total energy expenditure (TEE) by DLW and dietary intake using 7-day weighed records. EI was 98% of TEE in LR children, 95% in HR children and 86% in OB children. Although EI was similar in each group (LR, 7.03+/-1.26 MJ/day; HR, 7.30+/-1.46 MJ/day; OB, 7.55+/-1.67 MJ/day), obese +/-4.6%; P<0.05). There was a significant linear trend towards increasing fat intake (percentage energy) with increasing risk of obesity (P<0.05). While HR children were heavier and fatter than LR children (P<0.05), their EI and fat intake were not significantly greater (HR, 73+/-17 g, 37.3+/-4.4%). Dietary fat intake (percentage energy) was weakly but significantly related to body fatness (r(2)=0.05, P=0.02) by step-wise regression. Since energy from fat was the only macronutrient that was a significant predictor of body fatness, results were therefore analysed using quartiles of fat intake (percentage energy) as cut-offs. When grouped in this way children with the lowest intakes were leaner than those with the highest intakes (19.5+/-7.5 vs 24.9+/-9.4% body fatness; P<0.05). There was a significant trend for increasing fatness as fat intake increased (P<0.05). Fat intake is related to body fatness in childhood.


IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene transfer.
Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. T(H)17 cell populations secreting IL17A have been shown to have an important function in an increasing number of autoimmune diseases, including SS. In this study, we investigated the function of IL17A on SS development and onset. Adenovirus-5 vectors expressing either IL17R:fragment of crystallization (Fc) fusion protein or LacZ were injected through retrograde cannulation into the salivary glands of SS-susceptible (SS(S)) C57BL/6.NOD-Aec1Aec2 mice between 6 and 8 weeks of age (a pre-disease stage) or 15 and 17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4+IL17+T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their antinuclear antibodies repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. The capacity of the Ad5-IL17R:Fc-blocking factor to reduce SS pathology in SS(S) mice strongly suggests that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be effective in preventing glandular dysfunction.


Correlation between initial tumor enlargement and magnetic resonance imaging characteristics following linear accelerator-based stereotactic radiosurgery for acoustic neuromas.
Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.


Co-infection of dengue and Zika viruses mutually enhances viral replication in the mosquito Aedes aegypti.
The mosquito Aedes aegypti transmits two of the most serious mosquito-borne viruses, dengue virus (DENV) and Zika virus (ZIKV), which results in significant human morbidity and mortality worldwide. The quickly shifting landscapes of DENV and ZIKV endemicity worldwide raise concerns that their co-circulation through the Ae. aegypti mosquito vector could greatly exacerbate the disease burden in humans. Recent reports have indicated an increase in the number of co-infection cases in expanding co-endemic regions; however, the impact of co-infection on viral infection and the detailed molecular mechanisms remain to be defined. C6/36 (Aedes albopictus) cells were cultured in Dulbecco's modified Eagle medium/Mitsuhashi and Maramorosch Insect Medium (DMEM/MM) (1:1) containing 2% heat-inactivated fetal bovine serum and 1× penicillin/streptomycin solution. For virus propagation, the cells were infected with either DENV serotype 2 (DENV2) strain 16681 or ZIKV isolate Thailand/1610acTw (MF692778.1). Mosquitoes (Ae. aegypti UGAL [University of Georgia Laboratory]/Rockefeller strain) were orally infected with DENV2 and ZIKV through infectious blood-feeding. We first examined viral replication activity in cells infected simultaneously, or sequentially, with DENV and ZIKV, and found interspecies binding of viral genomic transcripts to the non-structural protein 5 (NS5). When we challenged Ae. aegypti mosquitos with both DENV2 and ZIKV sequentially to probe similar interactions, virus production and vector susceptibility to infection were significantly enhanced. Our results suggest that DENV2 and ZIKV simultaneously establishing infection in the Ae. aegypti mosquito vector may augment one another during replication. The data also implicate the homologous NS5 protein as a key intersection between the flaviviruses in co-infection, highlighting it as a potential target for vector control.


Mass Production of Customizable Core-Shell Active Materials in Seconds by Nano-Vapor Deposition for Advancing Lithium Sulfur Battery.
Rational design and scalable production of core-shell sulfur-rich active materials is vital for not only the practical success of future metal-sulfur batteries but also for a deep insight into the core-shell design for sulfur-based electrochemistry. However, this is a big challenge mainly due to the lack of efficient strategy for realizing precisely controlled core-shell structures. Herein, by harnessing the frictional heating and dispersion capability of the nanostorm technology developed in the authors' laboratory, it is surprisingly found that sulfur-rich active particles can be coated with on-demand shell nanomaterials in seconds. To understand the process, a micro-adhesion guided nano-vapor deposition (MAG-NVD) working mechanism is proposed. Enabled by this technology, customizable nano-shell is realized in a super-efficient and solvent-free way. Further, the different roles of shell characteristics in affecting the sulfur-cathode electrochemical performance are discovered and clarified. Last, large-scale production of calendaring-compatible cathode with the optimized core-shell active materials is demonstrated, and a Li-S pouch-cell with 453 Wh kg-1 @0.65 Ah is also reported. The proposed nano-vapor deposition may provide an attractive alternative to the well-known physical and chemical vapor deposition technologies.


Possible involvement of glutathione S-transferases in the cell growth of C6 astroglioma cells.
The changes of glutathione S-transferase activity were investigated using rat brain astroglioma C6 cells that were synchronized at different phases of the cell cycle. The enzyme showed two significant activity peaks at G2 and G1 phases. Furthermore, when C6 glioma cells were exposed to a culture medium supplemented with specific glutathione S-transferase inhibitors, ethacrynic acid and caffeic acid, cell growth was remarkably suppressed. These results suggest that glutathione S-transferases may be closely related to the mechanism of cell proliferation.


Guidelines for the uniform reporting of data for Medical Emergency Teams.
It is more than 15 years since the first Medical Emergency Team (MET) system was introduced to identify patients at risk and prevent serious adverse events in Liverpool Hospital, Sydney, Australia. Since then the MET system has been introduced to many other hospitals in Australia and around the world. Standardised and complete reporting of data related to MET activity is increasingly important to identify the role and benefits of the system and to facilitate quality improvement in health care in general. A uniform method for reporting data related to MET activity will aid interpretation of results, comparisons, review and changes to the MET system. The guidelines for uniform reporting of data in relation to MET activities used in our group of hospitals are presented. Future refinement and consensus agreement on the reporting of MET data internationally should enable comparisons between MET systems in several countries.


A Novel Type-2 Fuzzy C-Means Clustering for Brain MR Image Segmentation.
The fuzzy C -means (FCM) clustering procedure is an unsupervised form of grouping the homogenous pixels of an image in the feature space into clusters. A brain magnetic resonance (MR) image is affected by noise and intensity inhomogeneity (IIH) during the acquisition process. FCM has been used in MR brain tissue segmentation. However, it does not consider the neighboring pixels for computing the membership values, thereby misclassifying the noisy pixels. The inaccurate cluster centers obtained in FCM do not address the problem of IIH. A fixed value of the fuzzifier ( m ) used in FCM brings uncertainty in controlling the fuzziness of the extracted clusters. To resolve these issues, we suggest a novel type-2 adaptive weighted spatial FCM (AWSFCM) clustering algorithm for MR brain tissue segmentation. The idea of type-2 FCM applied to the problem on hand is new and is reported in this article. The application of the proposed technique to the problem of MR brain tissue segmentation replaces the fixed fuzzifier value with a fuzzy linguistic fuzzifier value ( M ). The introduction of the spatial information in the membership function reduces the misclassification of noisy pixels. Furthermore, the incorporation of adaptive weights into the cluster center update function improves the accuracy of the final cluster centers, thereby reducing the effect of IIH. The suggested algorithm is evaluated using T1-w, T2-w, and proton density (PD) brain MR image slices. The performance is justified in terms of qualitative and quantitative measures followed by statistical analysis. The outcomes demonstrate the superiority and robustness of the algorithm in comparison to the state-of-the-art methods. This article is useful for the cybernetics application.


The effect of SMAT-induced grain refinement and dislocations on the corrosion behavior of Ti-25Nb-3Mo-3Zr-2Sn alloy.
A nanocrystalline layer, which consists of pure β phase with high density of dislocations on Ti-25Nb-3Mo-3Zr-2Sn alloy, was fabricated by surface mechanical attrition treatment (SMAT). The corrosion behavior of the as-SMATed sample, together with the solution-treated coarse-grained and 200 °C annealed SMATed samples, was investigated by potentiodynamic polarization and electrochemical impedance spectroscope (EIS) techniques in physiological saline and simulated body fluid (SBF) solutions. The results demonstrate that the corrosion resistance of the studied alloy in both of the solutions considerably increased as the grain size decreased from microscale to nanoscale, which is ascribed to the dilution of segregated alloying elements at grain boundaries and the formation of more stable and much thicker passive protection films on the nanograined samples. Although the SMAT-induced grain refinement and dislocations both have positive effects on the corrosion behavior of the studied alloy, our post annealing experimental results indicate that the improved corrosion resistance is mainly due to the grain refinement.


Mother's assessments of term and pre-term infants with respiratory distress syndrome: reliability and predictive validity.
Assessments of term and preterm RDS infants were made by mothers on an adaptation of the Brazelton scale. The mother's assessments were not significantly different from those assessments made by trained clinicians, and both mothers and clinicians assigned less optimal ratings to the preterm infants. These ratings were correlated with Bayley motor scores at eight months. Mothers' assessments of infant temperament were made at four and eight months. These temperament ratings were significantly correlated with each other and with clinicians' ratings on the Brazelton neonatal and eight-month-Bayley Scales. These findings suggest that mothers' assessments are reliable and have some predictive validity during early infancy.


Persistent activity and memory in the entorhinal cortex.
The entorhinal cortex (EC) is an essential component of the medial temporal lobe long-term-memory system. Recently, Egorov et al. demonstrated that neurons in layer 5 of the EC show graded persistent activity: each neuron could maintain a constant rate firing over several minutes, even in the absence of input from other neurons. These findings suggest that layer-5 EC neurons could play a central role in the formation of associations among stimuli that occur at different times.


A case of moyamoya disease with progressive involvement from unilateral to bilateral.
A case of Moyamoya disease in a child starting with unilateral lesion and developing into bilateral involvement is reported. Angiographic findings at onset showed unilateral involvement, hence, it was filed as a "probable" case according to the diagnostic criteria of the Japanese Cooperative Research Committee. The carotid angiograms, on the other side were totally normal. Three years later the occlusive lesion became bilateral, to meet the criteria as a "definite" case. Clinical manifestations, angiograms, electroencephalograms, and positron emission tomograms in this case are presented, and the relation between the probable and definite cases is discussed.


Does the stigma shape the stutterer?
The Woods and Williams' (1976) study of Iowans' stereotypes about stuttering males was replicated using 11 speech clinicians and 16 classroom teachers in Virginia. Ratings of 23 possible characteristics were obtained for four hypothetical concepts (typical 8-year-old male, typical 8-year-old male stutter, typical adult male, and typical adult male stutterer) using a semantic differential format. The results of the Woods and Williams' (1976) research were confirmed. Stutters were expected by all rating groups to be more nonassertive, tense, insecure, and afraid to talk than nonstutterers. Not only were stereotype differences within professional groups quite small from one geographical region to the other, but classroom teachers held particularly unfavorable stereotypes of the stuttering boy in both studies. These results suggest the possibility that listener reactions could shape the stutterer's behavior.


Synthesis, pharmacologic and toxicologic study of carbonic and carbamic acid esters.
The results of the pharmacologic study of some synthesized derivatives of carbamic and carbonic acids show that the compounds are biologically active. They are less toxic than imipramine, and exert a marked excitation effect on the central nervous system. Some of the compounds (including PS-1, P-8-Y and PS-4) possess greater antidepressive action than imipramine.


Evaluation of visual acuity in dry AMD patients after microcurrent electrical stimulation.
To assess micro current to improve vision for dry age-related macular degeneration. Dry age-related macular degeneration is a major cause of blindness, disability, and severe erosion of quality of life, throughout the world. Beyond nutritional supplementation, there is no approved therapy. This was a prospective randomized sham controlled clinical trial for participants with confirmed dry AMD with documented visual loss. Participants were randomized three to one, to receive transpalpebral external micro current electrical stimulation with the MacuMira device. The Treatment group received four treatments in the first two weeks, and two further treatments at weeks 14 and 26. Differences in BCVA and contrast sensitivity (CS) were estimated with mixed-effects repeated measures analysis of variance. Change of visual acuity with ETDRS assessment of number of letters read (NLR) and contrast sensitivity at week 4 and 30, compared to the first visit, between 43 treatment and 19 sham control participants. The Sham Control group had NLR of 24.2 (SD 7.1) at baseline, 24.2 (SD 7.2) at 4 weeks, and 22.1 (SD7.4) at 30 weeks. The Treatment group had NLR of 19.6 (SD 8.9) at baseline, 27.6 (SD 9.1) at 4 weeks, and 27.8 (SD 8.4) at 30 weeks. The change in NLR from baseline in the Treatment compared to the Sham control group was 7.7 (95% CI 5.7, 9.7, p < 0.001) at 4 weeks and 10.4 (95% CI 7.8, 13.1, p < 0.001) at 30 weeks. There were similar benefits in CS. This pilot study of transpalpebral microcurrent demonstrated improved visual measures and is very encouraging as a potential treatment for dry AMD. NCT02540148, ClinicalTrials.gov.


Embedding patient and public involvement within research - How to set up a research patient ambassador group within a NHS trust.
Patient and public involvement in clinical research is vital to ensure the correct research questions are being asked to address patient and public's needs. Patient and public involvement groups can be set up within individual research departments and local NHS trusts to help guide researchers, but there is a lack of guidance on how to develop and implement patient and public involvement groups. In this paper, we discuss the vital role and benefits of patient and public involvement in clinical research. We also describe how a research patient ambassador group called the Clinical Research Ambassador Group was created at the Heart of England NHS Foundation Trust to offer some advice and guidance for researchers and clinicians wishing to form their own group within a NHS trust.


High-performance thermomagnetic generator controlled by a magnetocaloric switch.
Low grade waste heat accounts for ~65% of total waste heat, but conventional waste heat recovery technology exhibits low conversion efficiency for low grade waste heat recovery. Hence, we designed a thermomagnetic generator for such applications. Unlike its usual role as the coil core or big magnetic yoke in previous works, here the magnetocaloric material acts as a switch that controls the magnetic circuit. This makes it not only have the advantage of flux reversal of the pretzel-like topology, but also present a simpler design, lower magnetic stray field, and higher performance by using less magnetocaloric material than preceding devices. The effects of key structural and system parameters were studied through a combination of experiments and finite element simulations. The optimized max power density PDmax produced by our device is significantly higher than those of other existing active thermomagnetic, thermo, and pyroelectric generators. Such high performance shows the effectiveness of our topology design of magnetic circuit with magnetocaloric switch.


Development of a Dominant Negative Competence-Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia.
Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen responsible for a variety of diseases, including pneumonia, bacteremia, sepsis, meningitis and otitis media, with a death toll of >22 000 a year in the United States alone. Pneumococcus uses the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to initiate its attack on the host and establish an infection. In this work, we set out to: 1) develop a pan-group quorum sensing inhibitor that could effectively interact with both the pneumococcus ComD1 and ComD2 receptors; and 2) evaluate the utility of dominant-negative CSPs (dnCSPs) in attenuating pneumococcus infectivity. Our results highlight the potential of inhibiting the competence regulon as a therapeutic approach to combat pneumococcus infections.


Growth of mesometrial arteries in guinea pigs during pregnancy.
Massive growth was observed in mesometrial arteries supplying the placenta of the guinea pig in the first 60 days of pregnancy. The wet weight of the vessel wall increased 50 times, with an almost constant protein concentration. The DNA content rose 30 times. The length of the arteries increased 3.5 times and there was a 13-fold increase in the cross-sectional area of the wall. The changes in cross-sectional area were most pronounced in the peripheral part of the vessel. The observed changes followed an exponential time course. Histological sections showed proliferation, particularly of connective tissue with collagen fibres, while the synthesis of elastic material was suppressed. After parturition, involution with reduction of internal diameter occurred with a half-time of around five days.


Continuous Lighting Promotes Plant Growth, Light Conversion Efficiency, and Nutritional Quality of Eruca vesicaria (L.) Cav. in Controlled Environment With Minor Effects Due to Light Quality.
Light-emitting diode lamps can allow for the optimization of lighting conditions in artificial growing environments, with respect to light quality, quantity, and photoperiod extension, to precisely manage resources and crop performance. Eruca vesicaria (L.) Cav. was hydroponically cultured under three light treatments to investigate the effect on yield and nutritional properties of rocket plants. A treatment of (W-12h) having a12/12 h light/dark at 600 μmol m-2 s-1 provided by LEDs W:FR:R:B = 12:2:71:15 was compared with two treatments of continuous lighting (CL), 24 h light at 300 μmol m-2 s-1 provided by cool white LEDs (W-CL), and by LED R:B = 73:27 (RB-CL). CL enhanced the growth of the rocket plants: total fresh biomass, leaf fresh weight, and shoot/root ratio increased in W-CL, and leaf dry weight, leaf dry matter %, root fresh and dry weight, and specific leaf dry weight (SLDW) increased in RB-CL. Total carbon content was higher in RB-CL, whereas total nitrogen and proteins content increased in W-12h. Both W-CL and RB-CL increased carbohydrate content in the rocket leaves, while W-CL alone increased the sugar content in the roots. Fibers, pigments, antioxidant compounds, and malic acid were increased by CL regardless of the light spectrum applied. Nitrate was significantly reduced in the rocket leaves grown both in W-CL and RB-CL. Thus, the application of CL with low light intensity can increase the yield and quality value of rocket, highlighting that careful scheduling of light spectrum, intensity, and photoperiod can improve the performance of the crop.


Action of antibiotic oxacillin on in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) previously treated with homeopathic medicines.
Resistance to antibiotics is a major public health concern worldwide. New treatment options are needed and homeopathy is one such option. We sought to assess the effect of the homeopathic medicine Belladonna (Bell) and a nosode (biotherapy) prepared from a multi-drug resistant bacterial species, methicillin-resistant Staphylococcus aureus (MRSA), on the same bacterium. Bell and MRSA nosode were prepared in 6cH and 30cH potencies in 30% alcohol and sterile water, according to the Brazilian Homeopathic Pharmacopeia and tested on MRSA National Collection of Type Cultures (NCTC) 10442. We assessed in vitro bacterial growth, deoxyribonuclease (DNAase) and hemolysin activity, and in vitro bacterial growth in combination with oxacillin (minimum inhibitory concentration - MIC). All values were compared to control: 30% alcohol and water. In vitro growth of MRSA was statistically significantly inhibited in the presence of Bell and nosode 6cH and 30cH compared to controls (p < 0.0001); and with combination of Bell or nosode 6cH and 30cH and oxacillin (p < 0.001). Bell 30cH and nosode 6cH and 30cH significantly decreased bacterial DNAse production (p < 0.001) and reduced red blood cell lysis. Cultures of MRSA treated with Belladonna or MRSA nosode exhibited reduced growth in vitro, reduced enzymatic activity and became more vulnerable to the action of the antibiotic oxacillin. Further studies are needed on the biomolecular basis of these effects.


Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice.
Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been identified as a model for AMD and in particular for retinal angiomatous proliferation (RAP). In this study we examined the effect of cerium oxide nanoparticles (nanoceria) that have been shown to have catalytic antioxidant activity, on expression of 88 major cytokines in the retinas of Vldlr-/- mice using a PCR array. A single intravitreal injection of nanoceria at P28 caused inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors including Tslp, Lif, Il3, Il7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna3, Lep, and up-regulation of several cytokines and anti-angiogenic genes in the Vldlr-/- retina within one week. We used the Ingenuity Pathway Analysis software to search for biological functions, pathways, and interrelationships between gene networks. Many of the genes whose activities were affected are involved in cell signaling, cellular development, growth and proliferation, and tissue development. Western blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. These data suggest that nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases.


Effects of chronic sodium salicylate feeding on the impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia in streptozotocin diabetic rats.
The potential role of endogenous prostaglandins in glucagon and epinephrine responses to insulin-induced hypoglycaemia was studied in streptozotocin-diabetic and age-matched control adult male rats. Rats made diabetic with a single intravenous injection of streptozotocin (65 mg/kg) developed impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia by 80-100 days. Plasma glucagon levels in response to insulin-induced hypoglycaemia in streptozotocin-diabetic rats (167 +/- 67 pg/ml) were significantly lower (p less than 0.01) than those in control rats (929 +/- 272 pg/ml). Similarly, plasma epinephrine levels in hypoglycaemic state in streptozotocin-diabetic rats (11 +/- 8 pmol/ml) were also significantly lower (p less than 0.01) compared to control rats (37 +/- 13 pmol/ml). Streptozotocin-diabetic rats provided with sodium salicylate (25 mg/100 ml) in their drinking water from day one of diabetes exhibited prevention of the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia. About 80-100 days after the chronic sodium salicylate treatment in streptozotocin-diabetic rats, both plasma glucagon levels (1080 +/- 169 pg/ml) and plasma epinephrine levels (39 +/- 8 pmol/ml) were essentially identical to plasma glucagon levels (1074 +/- 134 pg/ml) and plasma epinephrine levels (37 +/- 5 pmol/ml) in control rats in hypoglycaemic state. These animals also exhibited an improvement in the diabetic state in that they had less severe hyperglycaemia and lack of weight gain. These results suggest that the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia may be related to altered prostaglandin levels in streptozotocin-diabetes.


A transport system for phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate in Salmonella typhimurium.
Salmonella typhimurium strain LT-2 was found to utilize phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for growth, but Escherichia coli strains did not. The following evidence suggests that this growth difference was due to the presence in Salmonella cells of an inducible phosphoglycerate permease distinct from previously studied transport systems: (a) The ability of cells to take up 3-phospho[14-C]glycerate was induced by growth in the presence of phosphoenolpyruvate, 2-phosphoglycerate, or 3-phosphoglycerate, but not glycerate, alpha-glycerophosphate, or other carbon sources tested. (b) Uptake of 3-phospho[14-C]glycerate was strongly inhibited by the three nonradioactive inducers of 3-phosphoglycerate uptake, but not by glycerate or alpha-glycerophosphate. (c) Mutants which lost the ability to utilize and take up 3-phosphoglycerate simultaneously lost the ability to utilize 2-phosphoglycerate and phosphoenolpyruvate, but not other compounds tested. (d) Mutant strains which constitutively synthesized the phosphoglycerate transport system could use both phosphoglycerates and phosphoenolpyruvate as sole sources of phosphate at low substrate concentrations. (e) A strain lacking alkaline and acid phosphatases could still grow with 3-phosphoglycerate as sole carbon source. Maximal rates of 3-phospho[14-C]glycerate uptake occurred at pH 6 in the presence of an exogenous energy source. The apparent Km for 3-phosphoglycerate uptake under these conditions was about 10-minus 4 M. The maximal uptake rate (but not the Km) was dependent on potassium ions. Although synthesis of the phosphoglycerate transport system appeared to be under adenosine 3:5-monophosphate control, glucose repressed induction only slightly. The genes controlling synthesis of the phosphoglycerate transport system (pgt genes) appeared to map at about 74 min on the Salmonella chromosome.


Lupus mastitis in systemic lupus erythematosus: a rare condition requiring a minimally invasive diagnostic approach.
Breast involvement is a rare event in SLE patients. The most frequent presentation is lupus panniculitis with skin erythema, tenderness, and parenchymal nodules. However, when breast masses are detected in SLE patients without significant superficial inflammation, it is mandatory to rule out breast carcinoma. Here, we report the case of a 47-year-old woman with an 18-year-long history of SLE, who presented with a suspicious breast mass. Since surgical trauma has been reported to be able to exacerbate breast inflammation in lupus mastitis, an ultrasound-guided minimally invasive Mammotome biopsy was performed to obtain tissue samples for histological and immunohistochemical examinations. Histology was consistent with lupus mastitis. The patient was already on mycophenolate mofetil and hydroxychloroquine. At the latest follow-up visit 6 years later, no progression of the breast lesion was observed.


The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus.
The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulin-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the β-cells and may constitute novel targets to prevent β-cell destruction in T1D.


The Role of Dual-Energy Computed Tomography in Musculoskeletal Imaging.
Dual-energy computed tomography (DECT) enables material decomposition and virtual monochromatic images by acquiring 2 different energy X-ray data sets. DECT can detect musculoskeletal pathologic conditions that CT alone cannot, and that would otherwise require MR imaging. In this review, the authors discuss several useful techniques and applications of DECT in musculoskeletal research: virtual monochromatic images, virtual noncalcium images, gout, iodine map, and tendons.


In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus.
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is a high-incidence tumor in southern China. Latent membrane proteins 2 (LMP2) is a subdominant antigen of EBV. The present study was to develop a dendritic cells (DCs)-based cancer vaccine (rAd-LMP2-DC) and to study its biological characteristics and its immune functions. Our results showed that LMP2 gene transfer did not alter the typical morphology of mature DC, and the representative phenotypes of mature DC (CD80, CD83, and CD86) were highly expressed in rAd-LMP2-DCs. The expression of LMP2 in rAd-LPM2-DCs was about 84.54%, which suggested efficient gene transfer. Transfected DCs markedly increased antigen-specific T-cell proliferation. The specific cytotoxicity against NPC cell was significantly higher than that in controls (p < 0.05), and enhanced with increased stimulations by transfected DCs. In addition, phenotypic analysis demonstrated that the LMP2-specific CTLs consisted of both CD4(+) and CD8(+) T cells. These results showed that development of DC-based vaccine by transfection with malignancy-associated virus antigens could elicit potent CTL response and provide a potential strategy of immunotherapy for EBV-associated NPC.


[Effect of bacterial infection on the lipid composition of carp blood lymphocytes].
The initial stage of bacterial infection is characterized by an increase in the level of total lipids and polyenoic fatty acids in membrane phospholipids of blood lymphocytes of carp (Cyprinus carpio L.). In the fish infected with aeromonads, changes in the ratios of fatty acids in phospholipids are similar for either lymphocytes, liver, or whole blood. The extent to which these changes are pronounced depends on the original physiological status of the fish.


A regiodivergent synthesis of ring a C-prenylflavones.
Capitalizing on the use of orthogonal protecting groups and the development of a modified Robinson flavone synthesis that avoids harsh acidic conditions, a regioselective synthesis of 6- and 8-prenylflavones from the same prenylated disilylated phloracetophenone (9) has been developed, targeting cannflavin B (1d), the COX-inhibiting principle of marijuana, and its unnatural isomer isocannflavin B (1e) as model compounds.


Assessment of Neurodevelopment and Growth in Congenital Hypothyroidism: Serial 6-Year Follow-up Study of 408 Patients.
The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect. To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention. We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages & Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation. The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score-weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction >.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes. The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed.


Ectopic overexpression of TaHsfA5 promotes thermomorphogenesis in Arabidopsis thaliana and thermotolerance in Oryza sativa.
Heat stress transcription factors (Hsfs) play an important role in regulating the heat stress response in plants. Among the Hsf family members, the group A members act upstream in initiating the response upon sensing heat stress and thus, impart thermotolerance to the plants. In the present study, wheat HsfA5 (TaHsfA5) was found to be one of the Hsfs, which was upregulated both in heat stress and during the recovery period after the stress. TaHsfA5 was found to interact with TaHsfA3 and TaHsfA4, both of which are known to positively regulate the heat stress-responsive genes. Apart from these, TaHsfA5 also interacted with TaHSBP2 protein, whose role has been implicated in attenuating the heat stress response. Further, its heterologous overexpression in Arabidopsis and Oryza sativa promoted thermotolerance in these plants. This indicated that TaHsfA5 positively regulated the heat stress response. Interestingly, the TaHsfA5 overexpression Arabidopsis plants when grown at warm temperatures showed a hyper-thermomorphogenic response in comparison to the wild-type plants. This was found to be consistent with the higher expression of PIF4 and its target auxin-responsive genes in these transgenics in contrast to the wild-type plants. Thus, these results suggest the involvement of TaHsfA5 both in the heat stress response as well as in the thermomorphogenic response in plants.


Augmented glutathione synthesis decreases acrolein toxicity.
We have shown recently that acrolein is more strongly involved in cell damage than reactive oxygen species during brain infarction. Thus, we tried to isolate cells with reduced susceptibility to acrolein toxicity to clarify how acrolein is detoxified under cell culture conditions. The IC(50) of acrolein in mouse mammary carcinoma FM3A cells and in neuroblastoma Neuro2a cells was 2.6 and 4.2μM, respectively, but in acrolein toxicity-decreasing FM3A (FM3A-ATD) cells and Neuro2a (Neuro2a-ATD) cells, it was 7.6 and 8.4μM, respectively. In both FM3A-ATD and Neuro2a-ATD cells, the concentration of glutathione (GSH) was increased, so that detoxification occurred through acrolein conjugation with GSH. In FM3A-ATD cells, the level of a rate-limiting enzyme of GSH synthesis, γ-glutamylcysteine ligase catalytic unit (GCLC), was increased through the reactivation of one inactive allele of GCLC genes in FM3A cells. In Neuro2a-ATD cells, phosphorylation of transcription factors (c-Jun and NF-κB) necessary for expression of genes for GCLC and glutathione synthetase (GSHS) involved in GSH synthesis was stimulated, so that transcription of two genes increased in Neuro2a-ATD cells. Phosphorylation of JNK (c-Jun N-terminal kinase), which catalyzes phosphorylation of c-Jun and NF-κB p65, was also increased in Neuro2a-ATD cells, suggesting that activation of JNK kinase is responsible for the increase in GSH. These results support the idea that GSH plays important roles in detoxification of acrolein, because GSH is increased in both FM3A-ATD and Neuro2a-ATD cells.


Analysis of a glucocorticoid-estrogen receptor chimera reveals that dimerization energetics are under ionic control.
Steroid receptors assemble at DNA response elements as dimers, resulting in coactivator recruitment and transcriptional activation. Our work has focused on dissecting the energetics associated with these events and quantitatively correlating the results with function. A recent finding is that different receptors dimerize with large differences in energetics. For example, estrogen receptor-α (ER-α) dimerizes with a ΔG=-12.0 kcal/mol under conditions in which the glucocorticoid receptor (GR) dimerizes with a ΔG≤-5.1 kcal/mol. To determine the molecular forces responsible for such differences, we created a GR/ER chimera, replacing the hormone-binding domain (HBD) of GR with that of ER-α. Cellular and biophysical analyses demonstrate that the chimera is functionally active. However, GR/ER dimerization energetics are intermediate between the parent proteins and coupled to a strong ionic linkage. Since the ER-α HBD is the primary contributor to dimerization, we suggest that GR residues constrain an ion-regulated HBD assembly reaction.


Assessment of heavy metal content and DNA damage in Hypsiboas faber (anuran amphibian) in coal open-casting mine.
The aims of the study were to determine the heavy metal content in the tissues of Hypsiboas faber from a coal mining area and to compare the DNA damage in the blood cells of these animals with that of animals living in an unpolluted area. The heavy metal content was detected according to the technique of Particle-Induced X-ray Emission (PIXE) and the DNA damage was assessed by the Comet assay. Our results reveal that the specimens of H. faber collected from the coal mining area exhibited elements of order Fe>Cu>Al>Zn>Rb>Mn>Br, independently of the organ. The values of Comet assay parameters (DNA damage index and DNA damage frequency) were significantly higher in specimens collected from the coal mining area than in the reference animals. Our study concludes that the coal mining residues are genotoxic to amphibians and may have adverse effects on soil, water, vegetation and wild animals.


Molecular characterization of a pattern recognition protein LGBP highly expressed in the early stages of mud crab Scylla paramamosain.
The early developmental stages of the mud crab Scylla paramamosain suffer from high mortality caused by pathogen infections; however, few immune associated factors are known. Lipopolysaccharide and β-1,3-glucan-binding protein (LGBP) functions as a typical pathogen recognition receptor and plays an important role in the innate immune system of invertebrates. In this study we characterized a LGBP gene (SpLGBP) which was highly expressed in the late embryonic, zoea I larval stage and hepatopancreas of S. paramamosain.. It encodes 364 amino acids, composed of several conserved domains like the bacterial glucanase motif. The recombinant SpLGBP protein (rSpLGBP) was obtained through the E.coli expression system, in which two 6◊His-tags were added to both C and N terminals during vector construction for the improvement of purification efficiency. In vivo the study showed that the SpLGBP mRNA was significantly up-regulated under Vibrio parahaemolyticus and a lipopolysaccharide (LPS) challenge in the hemocytes and hepatopancreas. The ELISA binding assay in vitro indicated that the rSpLGBP was capable of binding to LPSs and peptidoglycan (PGN). The rSpLGBP could agglutinate both G+ and G- bacteria in the presence of Ca2+. Our results suggest that SpLGBP may play an immunological role against pathogenic infection in the early developmental stages of S. paramamosain.


Staphylococcus aureus on the effect of expression of MMPs/TIMPs and uPA system in bovine mammary fibroblasts.
Bovine mammary fibrosis is characteristic of chronic in injury in response to diverse pathogens. Staphylococcus aureus (S.aureus) is a frequent cause of mastitis in bovine and is prone to persistent infection. Diverse studies have shown MMPs/TIMPs and uPA system as a potent target for the treatment of fibrosis. However, pathogenesis of S. aureus-induced mammary fibrosis has not been completely defined. BMFBs treated with heat-inactivated S. aureus (105, 106, and 108 CFU/mL) for 6, 12, 24, and 48 h. Total RNA and protein were isolated from the treatments and controls of BMFBs samples. MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, COL Ⅰ, uPA, uPAR and PAI-1 gene and protein expression were examined by RT-qPCR and Western blot analysis. Gelatin zymography assay was performed to assess the levels of MMP-2 and MMP-9 enzyme secreted. BMFBs treated with heat-inactivated S. aureus increased mRNA and protein expression levels of MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13, and heat-inactivated S. aureus induced TIMP-1, TIMP-2 and COL Ⅰ expression. There was a clear activation of MMP-2 in the presence of heat-inactivated S. aureus in the conditioned medium from the BMFBs, whereas MMP-9 was no significantly altered. Moreover, uPA system was activated in BMFBs to S. aureus. Activation of the uPA system together with its impact on the MMPs levels could play a significant role in S. aureus-induced BMFBs with mechanism of ECM metabolism, MMPs/TIMPs and uPA system could participate in bovine mammary fibrosis.


Anaerobiospirillum succiniciproducens phosphoenolpyruvate carboxykinase. Mutagenesis at metal site 1.
Anaerobiospirillum succiniciproducens phosphoenolpyruvate (PEP) carboxykinase catalyses the reversible metal-dependent formation of oxaloacetate (OAA) and ATP from PEP, ADP and CO(2). Mutations of PEP carboxykinase have been constructed where the residues His(225) and Asp(263), two residues of the enzyme's putative Mn(2+) binding site, were altered. Kinetic studies of the His225Glu, and Asp263Glu PEP carboxykinases show 600- and 16,800-fold reductions in V(max) relative to the wild-type enzyme, respectively, with minor alterations in K(m) for Mn(2+). Molecular modeling of wild-type and mutant enzymes suggests that the lower catalytic efficiency of the Asp263Glu enzyme could be explained by a movement of the lateral chain of Lys(248), a critical catalytic residue, away from the reaction center. The effect on catalysis of introducing a negatively charged oxygen atom in place of N(epsilon-2) at position 225 is discussed in terms of altered binding energy of the intermediate enolpyruvate.


Cost-Effectiveness of Single Versus Multifraction SABR for Pulmonary Oligometastases: The SAFRON II Trial.
The use of stereotactic ablative body radiation therapy (SABR) in advanced cancer care is increasing, yet the cost-effectiveness of single-fraction (SF) versus multifraction (MF) SABR in pulmonary oligometastases is unknown. A prespecified cost-effectiveness analysis was conducted of the Trans Tasman Radiation Oncology Group 13.01 - SAFRON II - randomized trial comparing SF with MF SABR in 87 patients with 133 pulmonary oligometastases. A partitioned survival model assessed costs and quality-adjusted life-years (QALY) over the within-trial period (4 years) and longer-term (10 years). Costs reflected a societal perspective, expressed in Australian dollars (A$) using 2020 prices and were estimated using patient level data on health care utilization for radiation therapy (including patient time), post-radiation systemic therapy and treatment of adverse effects. Quality of life was assessed using the EuroQoL EQ-5D-5L. The incremental cost-effectiveness ratio (ICER) was expressed as the cost per QALY gained for SF versus MF SABR, with uncertainty assessed using deterministic and probabilistic sensitivity analyses. SF cost less than MF for initial therapy (difference of A$1194/patient). Mean time to initiation of systemic drug therapy did not differ between arms (P = .94). Numerical differences in survival favoring SF resulted in greater overall health care use for the within-trial period. The within-trial ICER was A$15,821/QALY and A$23,265/QALY over the longer term. Results were most sensitive to the cost of postprogression therapies and utility values. The sensitivity analysis indicated that SF SABR has a 97% probability of being cost-effective at a willingness-to-pay of A$50,000/QALY. SF has lower initial costs and is highly likely to be cost-effective. Time to initiation of systemic therapy associated with disease progression is highly patient relevant and is a major driver of cost-effectiveness. Comparisons for SF SABR with nonradiation therapy approaches to the treatment of pulmonary oligometastases warrant further investigation.


Sex-specific associations of exposure to metal mixtures with telomere length change: Results from an 8-year longitudinal study.
Studies on the relationships between exposure to metal mixtures and telomere length (TL) are limited, particularly longitudinal studies. Few studies are available on the potential sex-specific associations between metal exposures and TL change. We examined blood metal concentrations and TL at baseline (August 2012) and follow-up (June 2020) among 316 participants in a ferro-manganese refinery. The least absolute shrinkage and selection operator (LASSO) followed by the generalized linear model (GLM) was applied to evaluate the associations between multiple-metal exposures and TL change (TL in 2012 minus TL in 2020). Bayesian kernel machine regression (BKMR) was applied to cope with metal mixtures and evaluate their joint effects on TL change. Among men, three statistical methods consistently showed rubidium was negatively associated with TL change (β [95% CI] = -2.755 [-5.119, -0.391] in the GLM) and dominated the negative overall effects of 10 metal mixtures (magnesium, manganese, iron, cobalt, copper, zinc, selenium, rubidium, cadmium, and lead) on TL change (posterior inclusion probabilities = 0.816). Among women, the GLM (β [95% CI] = 4.463 [0.943, 7.983]) and LASSO (β = 4.289) showed rubidium was positively associated with TL change. Interestingly, no significant association was observed between exposure to metal mixtures and TL change in overall participants (P > 0.05). Furthermore, stratified analysis showed significant relationships between rubidium and TL change in men (β = -2.744), women (β = 3.624), and current smokers (β = -3.266) (both P interaction <0.05). In summary, our findings underlined the steady and negative association between rubidium and TL change among men with potential sex-dependent heterogeneities. Further experimental studies are required to expound the underlying mechanisms.


Retained intravitreal lens fragments after phacoemulsification: complications and visual outcome in vitrectomized and nonvitrectomized eyes.
To evaluate the ocular complications and visual outcomes in vitrectomized and nonvitrectomized eyes with retained lens fragments after phacoemulsification. Department of Neurological, Psychiatric, and Ophthalmological Sciences, University of Padua, Padua, Italy. This prospective nonrandomized study comprised 36 consecutive patients with retained intravitreal lens fragments after phacoemulsification. Eighteen eyes had a pars plana vitrectomy (Group 1), and 18 eyes (Group 2) were treated with medication only. Intraocular pressure (IOP), intraocular inflammation, cystoid macular edema (CME), and best corrected visual acuity (BCVA) were evaluated 1, 3, and 6 months postoperatively. Ophthalmoscopy and B-scan echography showed that the lens fragments were significantly larger in Group 1 than in Group 2 (P < .03). An uncontrollable IOP rise and inflammation prompted an early vitrectomy in 11 eyes in Group 1. At the 6-month follow-up, the IOP with medications was acceptable in 2 and 5 eyes in Group 1 and Group 2, respectively. Intraocular inflammation was no longer detectable 1 month after vitrectomy but persisted during the entire follow-up in Group 2. At 3 months, 5 eyes in Group 1 and 13 in Group 2 had CME and at 5 months, 3 eyes and 1 eye, respectively, had CME. The difference between groups was significant at both follow-ups (P < .05). Three retinal detachments, 1 before and 2 after vitrectomy, occurred in Group 1. The mean BCVA in Group 1 was better than in Group 2 during the entire follow-up; however, the difference was significant at 3 months only (P < .5). At 6 months, 94.4% in Group 1 and 83.2% in Group 2 had a BCVA of 20/50 or better and 66.6% and 55.5%, respectively, attained at least 20/30. Intraocular inflammation, increased IOP, and CME were major complications in nonvitrectomized eyes after phacoemulsification; retinal detachment occurred in 2 vitrectomized eyes. In eyes with intravitreal lens fragments after phacoemulsification, vitrectomy can yield faster visual rehabilitation and better quality of vision. Conservative management is feasible at the price of long-term intraocular inflammation and slower restoration of comparable visual function.


A Fourteen-day Experience with Coronavirus Disease 2019 (COVID-19) Induced Acute Respiratory Distress Syndrome (ARDS): An Iranian Treatment Protocol.
COVID-19 is currently causing concern in the medical community as the virus is spreading around the world. It has a heavy global burden, particularly in low-income countries. The clinical spectrum of COVID-19 pneumonia ranges from mild to critically ill cases and Acute Respiratory Distress Syndrome. An expert panel was held and an internal protocol was developed to manage the COVID-19 induced ARDS according to WHO recommendations and NIH guidelines. Different therapeutic regimens were employed on this protocol based on the ARDS severity and the patients' special characteristics. The mortality rate, the rate of survivors, and non-survivors were reported. Of the 231 suspected cases of COVID-19 admitted to the hospital during two weeks, 72 patients were admitted to ICU with diagnosis confirmed by RT-PCR. In total, mortality in the ICU was 25% (n = 18) among ARDS patients over two weeks. COVID-19 induced ARDS is a major concern. The rapid progression of ARDS needs specific protocol based on patients' characteristics and rapid action.


Preliminary evaluation of Cyto-Rich: an improved automated cytology preparation.
A new cervical cytology monolayer preparation system called Cyto-Rich was evaluated. Using samples from 557 patients, Cyto-Rich monolayers were compared to matched conventional smears. After conventional smears were prepared and spray fixed, residual exfoliated cells were transferred to preservative fluid. The cell suspensions were gently disaggregated and the epithelial component enriched with gradient centrifugal sedimentation. The batched samples were then placed on the Cyto-Rich work station where slides are automatically prepared and stained. The results demonstrate that Cyto-Rich prepared monolayers are vastly superior to the conventional smears for cell presentation. While the study showed 99% overall concordance. Cyto-Rich improved the detection of low-grade cervical intraepithelial lesions.


Effect of electronic structure modulation and layer spacing change of NiAl layered double hydroxide nanoflowers caused by cobalt doping on supercapacitor performance.
Layered double hydroxides (LDHs) with high theoretical capacity have broad prospectsin energy storage applications. However, their slow charge transfer kinetics and easy agglomerate hinder their applications in high-performance supercapacitors. Herein, Co2+-doped nickel aluminum layered double hydroxides (NiAl-LDH-Co2+-x, x = 0, 0.3, 0.6, 0.9, 1.2, 1.5) have been designed and prepared by a convenient hydrothermal process. The multicomponent layer structure formed by cobalt doping facilitates sufficient penetration of the electrolyte and accelerates the charge transfer kinetics. Furthermore, the more open layer spacing and electronic interactions induced by Co2+ doping are conducive to accelerating ion de-intercalation, thereby further improving the kinetic behavior of charge storage. Benefiting from the unique microstructure and Co2+ doping effect, the prepared NiAl-LDH-Co2+-0.9 provides a superior specific capacity of 985 C g-1 at 1 A g-1. In addition, the assembled hybrid supercapacitor with the NiAl-LDH-Co2+-0.9 as the positive electrode provides a remarkable energy density of 22.51 Wh kg-1 at a power density of 800 W kg-1 and exhibits an excellent cycle life with 80 % capacity retention after 20,000 cycles. This study demonstrates the great potential of efficient microstructure design and doping strategy in enhancing the charge storage of electrode materials.


Size matching in lung transplantation: an evidence-based review.
The evidence base for size matching between donors and recipients in lung transplantation has not recently been reviewed in a comprehensive manner. Our aim in this study was to assimilate published studies that have addressed size matching of donors to recipients and to establish a pragmatic understanding of the range of lung sizes that may be used for lung transplantation. A comprehensive literature search was performed using Medline and PubMed up to and including September 2012, to identify scientific articles that relate to size matching between donors and lung transplant recipients. Seventy-two articles were identified, of which 21 had addressed the question of the impact of size mismatching on outcomes in lung transplantation. No study has specifically tested the consequences of intentionally mismatching above or below the hypothetical limits for double lung transplantation of a predicted total lung capacity for the donor of between 75% and 125% of the recipient predicted total lung capacity as set out in the ISHLT consensus report on lung donor acceptability criteria. Research is lacking that has robustly defined limits for size mismatch for single lung transplantation and for recipients with restrictive lung pathologies such as pulmonary fibrosis. Published research on the impact of size mismatching between lung transplant donors and recipients is limited by study design and size. It is centered on addressing the issue of mismatch in double lung transplantation in cohorts with a diagnostically heterogeneous make-up and in single lung transplant patients with chronic obstructive pulmonary disease.


Validity of estimating physical activity intensity using a triaxial accelerometer in healthy adults and older adults.
A triaxial accelerometer with an algorithm that could discriminate locomotive and non-locomotive activities in adults has been developed. However, in the elderly, this accelerometer has not yet been validated. The aim were to examine the validity of this accelerometer in the healthy elderly, and to compare the results with those derived in a healthy younger sample. Twenty-nine healthy elderly subjects aged 60-80 years (Elderly), and 42 adults aged 20-59 years (Younger) participated. All subjects performed 11 activities, including locomotive and non-locomotive activities with a Douglas bag while wearing the accelerometer (Active style Pro HJA-750C). Physical activity intensities were expressed as metabolic equivalents (METs). The relationship between the METs measured using the Douglas bag and METs predicted using the accelerometer was evaluated. A significant correlation between actual and predicted METs was observed in both Elderly (r=0.85, p<0.001) and Younger (r=0.88, p<0.001). Predicted METs significantly underestimated compared with actual METs in both groups (p<0.001). The mean of the errors was -0.6±0.6 METs in Elderly and -0.1±0.5 METs in Younger. The degree of underestimation increased with increasing METs in Elderly (p<0.001). A stepwise multiple regression analysis revealed that predicted METs, age, and weight were related to actual METs in both groups. The degree of correlation between predicted and actual METs was comparable in elderly and younger participants, but the prediction errors were greater in elderly participants, particular at higher-intensity activities, which suggests that different predicting equations may be needed for the elderly.


Chemical modification of erythropoietin: an increase in in vitro activity by guanidination.
Human recombinant erythropoietin (rHuEPO) was chemically modified with several group-specific reagents in order to study the role of each kind of amino-acid residue in its biological activity. Guanidination of the amino groups of the lysine residues yielded derivatives that showed higher activities in vitro than native rHuEPO, whereas amidination had no effect on the activity. By contrast, modification of the positive charges of the lysine residues to neutral or negative charges, such as in carbamylation, trinitrophenylation, acetylation or succinylation, caused a significant loss of rHuEPO activity. Chemical modification of other amino-acid residues, such as arginine and tyrosine residues or carboxyl groups, also led to loss of activity.


Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications.
Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation not fully reversible. However, a number of patients with COPD respond to bronchodilator agents. Some studies have shown polymorphisms in the b2-adrenergic (ADRb2) and muscarinic M2 and M3 receptors (CHRM) that may participate in the modulation of the receptor responses. This study was designed to investigate the existence and the role of adrenergic and muscarinic receptor polymorphisms and their functional impact in COPD. Eighty-two patients with COPD and 17 healthy smokers were recruited and screened for ADRb2 (T164I and R175R), for CHRM2 (rs1824024) and for CHRM3 (-513C/A and -492C/T). Among the polymorphisms studied our results was not able to demonstrate statistically significant association between the polymorphisms studied and COPD risk. Contrarily, we identified, in our COPD population, a significant association with the CHRM2 (rs1824024) polymorphism and disease severity, with lower lung function test values, frequent exacerbations, and poor response to anti-cholinergic drugs. These results suggest the potential role of receptor polymorphism assessment to discriminate newly COPD phenotypes. J. Cell. Physiol. 231: 1745-1751, 2016. © 2015 Wiley Periodicals, Inc.


Polyaniline nanofibers: acute toxicity and teratogenic effect on Rhinella arenarum embryos.
The fate and effect of nanomaterials in the environment is of paramount importance towards the technological application of the materials. This work shows the ecotoxicological potential of polyaniline (PANI) nanofibers in the larvae Rhinella arenarum by means of AMPHITOX test. Acute toxicity of PANI nanofibers towards embryos of the common South American toad R. arenarum (Anura: bufonidae) was evaluated in the premetamorphosis (stage 25) larvae. The exposure of R. arenarum larvae to at dose of 150, 250 and 400 mg L(-1) resulted in 100% viability within 96 h exposure. The embryos at 2-4 blastomers stage (early life stage teratogenic test) revealed that embryos were not killed and no teratogenic effects were observed when embryos were incubated with PANI nanofibers (150 and 250 mg L(-1)), while only a growth retardation of embryos was induced at levels of 250 mg PANI nanofibers L(-1). On the other hand, at 400 mg L(-1) concentration, a reduction in the body length of larvae and tail malformation was observed. This results suggest that a concentration-dependent toxicity is operative, typified by phenotypes that had abnormal body axes. The presence of PANI nanofibers in gut contents and its excretion by larval stages of R. arenarum was confirmed by UV-visible spectroscopy.


Anti-inflammatory and antinociceptive effects of an ethanol extract from Senna septemtrionalis.
Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1β, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1β, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.


Zinc and copper concentrations in leucocytes and erythrocytes in healthy adults and the effect of oral contraceptives.
The content of zinc and copper of whole blood, plasma, erythrocytes and white cells, has been measured in normal controls. The concentrations of zinc and copper in leucocytes are about seven and ten times respectively higher than those in erythrocytes. Women taking oral contraceptives showed significant increases in the concentrations of copper in plasma and whole blood but not in leucocytes or erythrocytes. Oral contraceptives did not alter the concentration of zinc in any of the fractions or in whole blood. These data provide a baseline for the assessment of the body status of zinc and copper in various disease states in which deficiencies may be present.


First record of the genus Phradis Förster (Hymenoptera, Ichneumonidae, Tersilochinae) from the Neotropical Region.
One new species of the genus Phradis, Phradis peruvianussp. n., from the mountainous part of Peruvian Amazonia, is described and illustrated. This is the first record of the genus from South America and the Neotropical region.


A review of renal disease in cystic fibrosis.
Kidney disease is becoming increasingly common in CF. This review looks at the effect of CFTR on the kidney, the problems with measuring renal function effectively in CF, the causes and incidence of renal dysfunction, and its pathophysiology. Strategies to reduce aminoglycoside toxicity are discussed.


Zinc- and cadmium-tolerant endophytic bacteria from Murdannia spectabilis (Kurz) Faden. studied for plant growth-promoting properties, in vitro inoculation, and antagonism.
This research aims to isolate and identify Zn- and Cd-tolerant endophytic bacteria from Murdannia spectabilis, identify their properties with and without Zn and Cd stress, and to investigate the effect of bacterial inoculation in an in vitro system. Twenty-four isolates could survive on trypticase soya agar (TSA) supplemented with Zn (250-500 mg L-1) and/or Cd (20-50 mg L-1) that belonged to the genera Bacillus, Pantoea, Microbacterium, Curtobacterium, Chryseobacterium, Cupriavidus, Siphonobacter, and Pseudomonas. Each strain had different indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC) deaminase and siderophore production, nitrogen fixation, phosphate solubilization, and lignocellulosic enzyme characteristics. Cupriavidus plantarum MDR5 and Chryseobacterium sp. MDR7 were selected for inoculation into plantlets that were already occupied by Curtobacterium sp. TMIL due to them have a high tolerance for Zn and Cd while showing no pathogenicity. As determined via an in vitro system, Cupriavidus plantarum MDR5 remained in the plants to a greater extent than Chryseobacterium sp. MDR7, while Curtobacterium sp. TMIL was the dominant species. The Zn plus Cd treatment supported the persistence of Cupriavidus plantarum MDR5. Dual and mixed cultivation showed no antagonistic effects between the endophytes. Although the plant growth and Zn/Cd accumulation were not significantly affected by the Zn-/Cd-tolerant endophytes, the inoculation did not weaken the plants. Therefore, Cupriavidus plantarum MDR5 could be applied in a bioaugmentation process.


Detergent effects on enzyme activity and solubilization of lipid bilayer membranes.
Over 50 detergents were tested to establish which would be most effective in releasing proteins from membrane-bounded compartments without denaturing them. Various concentrations each of detergent were tested for two activities: (1) solubilization of egg phospholipid liposomes as measured by reduction of turbidity and (2) effect of detergent concentration on the activities of soluble, hydrolytic enzymes. Those detergents most effective in solubilizing 0.2% lipid and least detrimental to enzymes were five pure, synthetic compounds recently introduced: CHAPS, CHAPSO, Zwittergents 310 and 312, and octylglucoside. Industrial detergents were generally much inferior, insofar as they solubilized membranes inefficiently and/or inactivated certain hydrolytic enzymes readily. The five detergents were characterized by (a) an unusually high critical micelle concentration and (b) a preference for forming mixed micelles with lipids instead of forming pure micelles, as indicated by an ability to solubilize lipid at concentrations of detergent significantly below the critical micelle concentration. This characteristic permits solubilization of high concentrations of membrane below the critical micelle concentration of the detergent so that protein denaturation is minimized. A generally applicable guideline that emerged from this study is that detergents should be used at approximately their critical micelle concentration which should not be exceeded by the concentration of membrane. Similar considerations should apply to the use of detergents in purifying and reconstituting intrinsic membrane proteins.


Temporal changes in allele frequencies but stable genetic diversity over the past 40 years in the Irish Sea population of thornback ray, Raja clavata.
Rays and skates are an unavoidable part of the by-catch in demersal fisheries. Over the past 40 years, the thornback ray (Raja clavata) has decreased in numbers and even disappeared in some areas, leading to concerns about genetic risk. For this reason, the effective population size (N(e)), the migration rate (m) and temporal changes in the genetic diversity were estimated for the population of thornback rays in the Irish Sea and Bristol Channel. Using genotyped, archived and contemporary samples (1965 and 2003-2004), N(e) was estimated at 283 individuals (95% CI=145-857), m at 0.1 (95% CI=0.03-0.25) and the N(e)/N ratio between 9 x 10(-5) and 6 x 10(-4). Although these results must be treated with caution, due to the small sample sizes, this is the first attempt to estimate N(e) in an elasmobranch species. The low N(e)/N ratio suggests that relatively few individuals contribute to the next generation. The combined effect of sex bias, inbreeding, fluctuations in population size and, perhaps most important, the variance in reproductive success may explain the low N(e)/N ratio. In addition, the relatively high gene flow between Irish Sea population and other source populations is likely to have had an impact on our estimate, which may be more relevant at the metapopulation scale. No significant loss of genetic diversity was found over the 40-year timeframe and long-term maintenance of the genetic diversity could be due to gene flow.


Mid-IR dispersion spectroscopy - A new avenue for liquid phase analysis.
Mid-IR dispersion spectroscopy is an attractive, novel approach to liquid phase analysis that extends the possibilities of traditional methods based on the detection of absorption via intensity attenuation. This technique detects inherent refractive index changes (phase shifts) induced by IR light interaction with absorbing matter. In contrast to classic absorption spectroscopy, it provides extended dynamic range, baseline-free detection, constant sensitivity, and inherent immunity to power fluctuation. In this paper, we provide a detailed experimental and theoretical characterization and verification of this method with special focus on broadband liquid sample analysis. For this purpose, we develop a compact benchtop dispersion spectroscopy setup based on an EC-QCL coupled to a Mach-Zehnder interferometer. Phase-locked interferometric detection enables to fully harness the advantages of the technique. By instrument operation in the quadrature point combined with balanced detection, the full immunity towards laser power fluctuations and the environmental noise can be achieved. On the example of ethanol (0.5-50% v/v) dissolved in water, it is experimentally demonstrated that changes of the refractive index function are linearly related to concentration also for strongly absorbing, highly concentrated samples beyond the validity of the Beer-Lambert law. Characterization of the sensitivity and noise behavior indicates that the optimum applicable pathlength for liquid analysis can be extended beyond the ones for absorption spectroscopy. Experimental demonstration of the advantages over classical absorption spectroscopy illuminates the potential of dispersion spectroscopy as upcoming robust and sensitive way of recording IR spectra of liquid samples.


Hypoplastic left heart syndrome: new developments and current controversies.
Prior to 1980, the diagnosis of hypoplastic left heart syndrome (HLHS) was almost uniformly lethal. Over the past 25 years, the development of operative options, including staged surgical palliation and infant heart transplant, have resulted in major improvements in survival and quality-of-life outcomes. Throughout this period, the optimal treatment strategy for children with HLHS has continued to be controversial. Current advances include fetal diagnosis, medical management, catheter intervention and operative techniques, and hold great promise for further improvements. However, as new techniques continue to evolve, controversies will continue to arise. This article will explore the treatment strategies for children with HLHS and review current controversies surrounding this complex congenital cardiac disease.


The ethnic variable and problem drinking in a select sample of southwestern two-year multicultural college students.
Five hundred and ninety-two Anglo, Mexican American, and American Indian students from nine selected 2-year colleges in the Southwest were given a self-administered questionnaire with items related to problem drinking (dependent variable) and various social psychological and demographic information (independent variables). Analyses included discriminant analysis, chi square, and eta. While ethnicity per se contributed little to the discrimination of problem from nonproblem drinkers, several other variables provided an overall correct classification (discrimination) rate of 79.73%. There variables were, in order of discriminating power: neighborhood people drink, veteran status, live life differently, close friend with drinking proble, drink because acquaintances drink, and age. It is hypothesized that the psychological principle of individual differences, and the significance of some other study variables, may haver overshadowed any ethnic effect. Measurement problems in this area are discussed as well as some potential research directions.


Is robotic-assisted radical cystectomy (RARC) with intracorporeal diversion becoming the new gold standard of care?
Totally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue. We assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion? (A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery. RARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.


Calcium-induced aggregation and fusion of mixed phosphatidylcholine-phosphatidic acid vesicles as studied by 31P NMR.
1. The transbilayer distribution of the phospholipids in sonicated egg phosphatidylcholine-phosphatidic acid vesicles and the interaction of Ca2+ with these vesicles was studied by 31P NMR. 2. Over a wide composition range the bilayer of these vesicles has a symmetrical phospholipid composition. 3. With ratios of Ca2+ to phosphatidic acid in the outer monolayer of the vesicles up to 0.3, Ca2+ induces vesicle aggregation. The extent of aggregation is increased by the Ca2+ concentration in the medium and the outer monolayer concentration of phosphatidic acid. The vesicle aggregation can be fully reversed by chelating Ca2+. 4. When the ratio exceeds 0.5 Ca2+ induces vesicle fusion. The fusion is maximal for vesicles containing both phosphatidylcholine and phosphatidic acid. The data suggest that Ca2+-induced lateral phase separations make the bilayer more susceptible to fusion.


Estimate of the prevalence of subjects with chronic diseases in a province of Northern Italy: a retrospective study based on administrative databases.
To find a definition of chronic disease based on literature review and to estimate the population-based prevalence rate of chronicity in a province in Northern Italy. Retrospective observational study based on administrative databases. Archives of the National Health Service that contain demographic and administrative information linked with the archives of ticket exemptions (2000-2019), the hospital discharge and drug prescriptions (2016-2019). Subjects who lived in Vercelli Local Health Authority, a Northern Italian province (Piedmont region), and were alive in December 2019. Prevalence of subjects with at least one chronic disease identified by administrative sources and stratification of population according to the number of comorbidities. The pathologies considered were: chronic ischaemic heart disease, congestive heart failure, cardiac arrhythmias, hypertension, stroke, neoplasm, asthma, chronic obstructive pulmonary disease, diabetes, thyroid disorders, osteoporosis, rheumatoid arthritis, chronic kidney disease, dementia, autism spectrum disorder, depression, schizophrenia, hepatitis, HIV and substance use disorders. Our target population was about 164 344 subjects. The overall prevalence of subjects with at least one chronic condition was 21.43% (n=35 212): 19 541 were female and 15 671 were male with a raw prevalence of 22.96% and 19.77%, respectively. The overall prevalence increases with age until 85 years old, then a decrease is observed. Moreover, 16.39% had only one pathology, 4.30% two diseases and 0.74% had a more complex clinical condition (more than three diseases). Despite the difficulty of having a unique definition of chronic disease, the prevalence obtained was coherent with the estimates reported by other national surveillance systems such as Passi and Passi d'Argento. Underestimates were observed when international comparisons were done; however, when we used less stringent definitions of chronic diseases, similar results were obtained.


Short- and long-term results of total arch replacement: Comparison between island and debranching techniques.
The 2 most acceptable techniques for reimplantation of the supra-aortic vessels in total arch replacement include the branched graft technique (debranching) or en bloc technique (island). We aim to review our experience with total arch replacement and report short- and long-term outcomes from a high-volume center dedicated to surgery for the thoracic aorta. The aortic surgery database was queried to identify all consecutive patients undergoing total arch replacement between 1997 and 2022. Of the 426 patients who underwent total arch replacement, 303 (71%) received the island technique and 123 (29%) received the debranching approach. Operative and long-term outcomes were compared using multivariable models. The debranching group was younger (64 ± 14 years vs 69 ± 12 years, P = .001), had undergone more previous cardiac operations (54.5% vs 27.4%, P < .001), and had more connective tissue disorder (20.3% vs 4.6%, P < .001). The debranching approach was associated with longer total circulatory arrest time (47 ± 15 minutes vs 37 ± 10 minutes, P < .001) and cardiac ischemic time (116 ± 41 minutes vs 100 ± 37 minutes, P < .001). More patients in the debranching group received blood products intraoperatively or postoperatively (56.1% vs 42.9%, P = .018). All other early outcomes did not differ between groups. Overall operative mortality was 1.4% (2.4% vs 1%, P = .486); the incidence of major postoperative complications was 6.3% (5.7% vs 6.6%, P = .897). Ten-year survival was 80% (78% vs 80.9%, log-rank P = .356). Multivariable Cox regression analysis demonstrated that neither surgical approach was associated with survival advantage (hazard ratio, 1.18; 0.73-1.89; P = .495). Debranching requires a longer operative time, with similar early and long-term outcomes. Preoperative comorbidity, not surgical technique, predicts major adverse events and long-term survival.


Effect of thyrotropin-releasing hormone on dog thyroid in vitro.
The in vitro action of thyrotropin-releasing hormone (TRH) on the cyclic AMP level and iodine metabolism in dog thyroid, has been studied. TRH inhibited cyclic AMP accumulation and subsequent secretion in slices stimulated by thyrotropic hormone (TSH), prostaglandin E1, cholera toxin and to a lesser extent forskolin. The effect of TRH was suppressed in a medium deprived of calcium or in the presence of isobutylmethylxanthine. TRH also stimulated iodide binding to proteins, but not cyclic GMP accumulation. Although all these characteristics of TRH action on dog thyroid fit those of prostaglandin F1 alpha in this tissue, TRH effects were not relieved by indomethacine. The possibility of a TRH action through other known inhibitors of the cyclic AMP system in dog thyroid such as: acetylcholine, alpha-adrenergic agents, adenosine, iodide were checked and ruled out. The possible involvement of other neurotransmitters, such as ATP or vasoactive intestinal peptide were studied but could not be substantiated. Our data suggest the existence of a direct negative action of TRH on the thyroid itself besides its stimulatory role at the pituitary level. The great variability of the TRH effect was overcome by pretreatment of the dog by pyridostigmine, an acetylcholinesterase inhibitor.


Dissociation of obesity, hypercholesterolemia and diabetes from atherosclerosis in ob/ob mice.
Genetically obese, diabetic and hypercholesterolemic C57BL/6J-ob/ob mice were placed on Purina Laboratory Chow containing 2% cholesterol for up to 4 months. They developed higher plasma cholesterol levels and accumulated an increased quantity of cholesterol in the liver but failed to develop atherosclerotic lesions in the aorta as would be expected in an obese, diabetic and hypercholesterolemic human adult.


Towards the chiral metabolomics: Liquid chromatography-mass spectrometry based DL-amino acid analysis after labeling with a new chiral reagent, (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidine-2-carboxylate, and the application to saliva of healthy volunteers.
A novel triazine-type chiral derivatization reagent, i.e., (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl) pyrrolidine-2-carboxylate (DMT-(S)-Pro-OSu), was developed for the highly sensitive and selective detection of chiral amines and amino acids by UPLC-MS/MS analysis. The enantiomers of amino acids were easily labeled with the reagents at room temperature within 40 min in an alkaline medium containing triethylamine. The diastereomers derived from proteolytic amino acids, except serine, were well separated under isocratic elution conditions by reversed-phase chromatography using an ODS column (Rs=1.2-9.0). DL-Serine was separated by use of an ADME column which has relatively higher polar surface than the conventional ODS column. The characteristic product ions, i.e., m/z 195.3 and m/z 209.3, were detected from all the diastereomers by the collision-induced dissociation of the protonated molecule. A highly sensitive detection on the amol-fmol level was obtained from the selected reaction monitoring (SRM) chromatogram. The chiral amines (e.g., adrenaline and noradrenaline) labeled with DMT-(S)-Pro-OSu were also well separated and sensitively detected by the present procedure. The method using DMT-(S)-Pro-OSu was used for the determination of DL-amino acids in the human saliva from healthy volunteers. Various L-amino acids were identified in the saliva. Furthermore, D-alanine (D-Ala) and D-proline (D-Pro) were also detected in relatively high concentrations (>5%). The ratio was higher in male saliva than in female saliva. However, the difference in the ratio of D-Ala for one day was not very high and the effect of foods and beverage seemed to be negligible. Based on the results using L-Ala-d3, the D-Ala in saliva seemed to be produced due to the racemization with some enzymes such as racemase. The racemization reaction was reversible, i.e., D-Ala-d3 was also racemized to L-Ala-d3 in saliva. Thus, care should be taken during the analysis of DL-amino acids in saliva. The present method using DMT-(S)-Pro-OSu may be applicable for the determination of chiral amine metabolomics, because the resulting derivatives produce the same product ions without relation to the compounds and show highly sensitive detection in the SRM mode of MS/MS. Consequently, DMT-(S)-Pro-OSu seems to be a useful chiral derivatization reagent for the determination of amines and amino acids in biological samples.


Spectroscopic study of the temperature-dependent conformation of glucoamylase.
Vibrational circular dichroism, electronic circular dichroism and infrared absorption with Fourier self-deconvolution have been used for a conformational study of the small form, G2, of glucoamylase, 1,4-alpha-D-glucan glucohydrolase from Aspergillus niger (EC 126.96.36.199) in aqueous solution. From the temperature dependence of spectra measured from 25 degrees C to 60 degrees C it was seen that the helical content is relatively constant to 50 degrees C and then sharply decreases by a factor of more than three by 60 degrees C. This decrease in helix is primarily compensated by a rise in the fraction of beta-sheet; but bend, turn and 'other' components also increase. By comparison of the three techniques, it was determined that the electronic CD analysis was quantitatively in error due to interference by glycosidic residues. The inherent resolution of the vibrational techniques, FTIR and VCD, avoids such interference.