Making the journey with me: a qualitative study of experiences of a bespoke mental health smoking cessation intervention for service users with serious mental illness.
Smoking is one of the major modifiable risk factors contributing to early mortality for people with serious mental illness. However, only a minority of service users access smoking cessation interventions and there are concerns about the appropriateness of generic stop-smoking services for this group. The SCIMITAR (Smoking Cessation Intervention for Severe Mental Ill-Health Trial) feasibility study explored the effectiveness of a bespoke smoking cessation intervention delivered by mental health workers. This paper reports on the nested qualitative study within the trial. Qualitative semi-structured interviews were conducted with 13 service users receiving the intervention and 3 of the MHSCPs (mental health smoking cessation practitioners) delivering the intervention. Topic guides explored the perceived acceptability of the intervention particularly in contrast to generic stop-smoking services, and perceptions of the implementation of the intervention in practice. Transcripts were analysed using the Constant Comparative Method. Generic services were reported to be inappropriate for this group, due to concerns over stigma and a lack of support from health professionals. The bespoke intervention was perceived positively, with both practitioners and service users emphasising the benefits of flexibility and personalisation in delivery. The mental health background of the practitioners was considered valuable not only due to their increased understanding of the service users' illness but also due to the more collaborative relationship style they employed. Challenges involved delays in liaising with general practitioners and patient struggles with organisation and motivation, however the MHSCP was considered to be well placed to address these problems. The bespoke smoking cessation intervention was acceptable to service users and the both service users and practitioners reported the value of a protected mental health worker role for delivering smoking cessation to this group. The results have wider implications for understanding how to achieve integrated and personalised care for this high-risk population and further underscore the need for sensitised smoking cessation support for people with serious mental illness. Current Controlled Trials ISRCTN79497236 . Registered 3(rd) July 2009.


Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms.
Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.


Classical Hodgkin lymphoma occurring in association with progressive transformation of germinal center.
Progressive transformation of germinal center (PTGC) represents an asymptomatic persistent form of lymphadenopathy. We present a case of classical Hodgkin lymphoma occurring in association with PTGC. The patient was a 60-year-old woman who had noted swelling of the submandibular lymph nodes. Histopathologically, the enlarged lymph nodes appeared as multiple nodules with ill-defined and irregularly expanded germinal centers. Immunohistochemical studies indicated that the germinal center cells comprised B cells that were positive for CD10 and CD20, and negative for bcl-2. Enlarged vascular endothelial cells were present in the interfollicular areas. CD30-positive Hodgkin & Reed-Sternberg cells were seen between the interfollicular area and the mantle zone, and were surrounded by CD3-positive T-cells. In situ hybridization studies demonstrated no expression of Epstein-Barr virus-encoded small RNA in the Hodgkin & Reed-Sternberg cells. A diagnosis of classical Hodgkin lymphoma complicated by PTGC was made from the lymph node specimen.


Facial necrotizing fasciitis from an odontogenic infection.
Necrotizing fasciitis (NF) is defined as rapidly progressive necrosis of subcutaneous fat and fascia. It is a rare but life-threatening infection characterized by a progressive, usually rapid, necrotizing process of the subcutaneous tissues and fascial planes. The condition is commonly described in the extremities, abdominal wall, and perineum but rarely seen in the head and neck. The diagnosis of NF depends mainly on clinical features, which are not always observable, so that the disease is often diagnosed late in its course, resulting in high mortality. Broad-spectrum antibiotics, aggressive surgical treatment and supportive therapy are the most widely accepted modalities of successful treatment. We describe a case of necrotizing fasciitis of the head and neck, arising from odontogenic origin.


Horizontally aligned single-walled carbon nanotube on quartz from a large variety of metal catalysts.
Horizontally aligned single-walled carbon nanotubes (SWNTs) are highly desired for SWNT device applications. A large variety of metals including Fe, Co, Ni, Cu, Pt, Pd, Mn, Mo, Cr, Sn, Au, Mg, and Al successfully catalyzed the growth of such tubes on stable temperature (ST)-cut quartz by lattice guidance. In addition, Mg and Al were presented to produce random and aligned SWNTs for the first time. A hypothesis is proposed in which the precipitated carbon shell on the outer surface of the metal catalysts guides the alignment along the crystal lattice but not the catalysts themselves. By elucidating the role of the catalysts, an understanding of the aligned growth mechanism on quartz is further improved. Moreover, a simple "scratch" method by a razor blade such as the carbon steel and tungsten carbide (with 9% cobalt) is presented to pattern the "catalysts" without any complex processing steps such as lithography for the aligned SWNT growth.


Asymmetric dearomatizing spirolactonization of naphthols catalyzed by spirobiindane-based chiral hypervalent iodine species.
This report details the development of a spirobiindane-based chiral hypervalent iodine reagent, especially focusing on its structural elucidation for effective asymmetric induction of the chiral spiro center during the oxidative dearomatizing spirolactonization of naphthols. In this study we synthesized a new series of ortho-functionalized spirobiindane catalysts and demonstrated that the enantioselectivity can be dramatically improved by the presence of the substituents ortho to the iodine atom. The structural elucidation of a spirobiindane-based hypervalent iodine catalyst has led to further improvement in the stereoselective construction of the spiro center during the oxidative dearomatizing spirolactonization of naphthols. Thus, catalytic oxidation with the highest reported level of enantioselectivity in hypervalent iodine chemistry has been achieved with also an excellent level of asymmetric induction (92% ee for substrate 3a). As a result, this study, dealing with a series of modified iodine catalysts, can provide important clues about the transition state and reaction intermediate to help scientists understand the origin of the stereoselectivity. A plausible transition-state model and intermediate in the reaction for the stereoselective formation of spirolactone products are postulated by considering the ortho-substituent effect and the results of X-ray analysis. In this reaction model, the high enantiomeric excess obtained by using the spirobiindane catalysts could be well explained by the occupation of the equatorial site and extension of the surroundings around the hypervalent iodine bonds by the introduced ortho-substituent. Thus, this study would contribute to estimation of the chiral hypervalent iodine compounds in asymmetric reactions.


Prevalence of diabetic nephropathy among Type 2 diabetic patients in some of the Arab countries.
Type 2 diabetes mellitus (DM) is a public health concern worldwide and an important cause of morbidity and mortality. Type 2 DM is associated with microvascular and macrovascular complications. Diabetic nephropathy (DN), which is characterized by proteinuria, is one of the most serious long-term microvascular complications of DM. The proportion of DN is increasing worldwide. DN is the leading cause of chronic kidney diseases and end-stage renal disease, which constitutes the major workload of dialysis centers worldwide. Microalbuminuria (MA) is the earliest sign of DN, so the early detection of MA and early control of diabetes retards the progression of DN.


Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) regulates fibroblast growth factor receptor substrate 2 (FRS2) by targeting microRNA (miR)-29-3p in hypertrophic scar fibroblasts.
Long non-coding RNAs (lncRNAs) play crucial roles in human diseases. However, the detailed role of lncRNAs in hypertrophic scar fibroblasts (HSFs) is inadequately understood. This study aimed to investigate the potential role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in hypertrophic scarring. Expression of lncRNAs, miRNAs, and genes were detected by polymerase chain reaction; protein expression was evaluated using western blotting. Cellular function was determined using the CCK-8 assay. The interaction between microRNA (miR)-29-3p and NEAT1 or fibroblast growth factor receptor substrate 2 (FRS2) was verified by luciferase and RNA pull-down assays. The results showed that NEAT1 was overexpressed in the hypertrophic dermis and in HSFs. However, knockdown of NEAT1 suppressed the proliferation and extracellular matrix (ECM) production of HSFs. Moreover, NEAT1 functioned as a competing endogenous RNA to upregulate FRS2 by sponging miR-29-3p. Downregulation of miR-29-3p or overexpression of FRS2 antagonized the effects of NEAT1 knockdown and promoted HSF proliferation and ECM release. In conclusion, NEAT1 knockdown protected against hypertrophic scarring by modulating the miR-29-3p/FRS2 axis, which is a viable target in scar treatment.


YS-TaS2 and YxLa1-xS-TaS2 (0 ≤ x ≤ 1) Nanotubes: A Family of Misfit Layered Compounds.
We present the analysis of a family of nanotubes (NTs) based on the quaternary misfit layered compound (MLC) YxLa1-xS-TaS2. The NTs were successfully synthesized within the whole range of possible compositions via the chemical vapor transport technique. In-depth analysis of the NTs using electron microscopy and spectroscopy proves the in-phase (partial) substitution of La by Y in the (La,Y)S subsystem and reveals structural changes compared to the previously reported LaS-TaS2 MLC-NTs. The observed structure can be linked to the slightly different lattice parameters of LaS and YS. Raman spectroscopy and infrared transmission measurements reveal the tunability of the plasmonic and vibrational properties. Density-functional theory calculations showed that the YxLa1-xS-TaS2 MLCs are stable in all compositions. Moreover, the calculations indicated that substitution of La by Sc atoms is electronically not favorable, which explains our failed attempt to synthesize these MLC and NTs thereof.


Boosting the Performance of Organic Photodetectors with a Solution-Processed Integration Circuit toward Ubiquitous Health Monitoring.
Organic photodetectors, as an emerging wearable photoplethysmographic (PPG) technology, offer exciting opportunities for next-generation photonic healthcare electronics. However, the mutual restraints among photoresponse, structure complexity, and fabrication cost have intrinsically limited the development of organic photodetectors for ubiquitous health monitoring in daily activities. Here, an effective route to dramatically boost the performance of organic photodetectors with a solution-processed integration circuit for health monitoring application is reported. Through creating an ideal metal-semiconductor junction interface that minimizes the trap states within the device, solution-printed organic field-effect transistors (OFETs) are achieved with an ultrahigh signal amplification efficiency of 37.1 S A-1 , approaching the theoretical thermionic limit. Consequently, monolithic integration of the OFET with an organic photoconductor enables the remarkable amplification of photoresponse signal-to-noise ratio by more than four orders of magnitude from 5.5 to 4.6 × 105 , which is able to meet the demand for accurately extracting physiological information from the PPG waveforms. This work offers an effective and versatile approach to greatly enhance the photodetector performance, promising to revolutionize health monitoring technologies.


Binding of urokinase to plasma proteinase inhibitors.
125I-labelled urokinase was incubated with plasma and plasminogen free plasma, and the incubation mixtures were analyzed by agarose gel electrophoresis. Autoradiography demonstrated that non-reacted urokinase remained around the slit and that complex-formation with inhibitors altered the migration and resulted in two bands, a major one and a minor one. Crossed immunoelectrophoresis combined with autoradiography showed that the major band contained a complex between alpha 2-antiplasmin and urokinase. The minor band contained a complex between alpha 2-macroglobulin and urokinase. Also di-isopropylfluorophosphate-inactivated urokinase was bound to alpha 2-macroglobulin but not to alpha 2-antiplasmin. Thus, an intact active site of urokinase is not necessary for complex formation with alpha 2-macroglobulin.


Dietary sodium to potassium ratio and the incidence of hypertension and cardiovascular disease: A population-based longitudinal study.
There is an interaction between dietary sodium/potassium intake in the pathogenesis of hypertension (HTN) and cardiovascular disease (CVD). The aim of this study was to investigate the association of dietary sodium to potassium (Na/K) ratio and the risk of HTN and CVD in a general population of Iranian adults. In this prospective cohort study, adults men and women with complete baseline data were selected from among participants of the Tehran Lipid and Glucose Study and were followed up for 6.3 years for incidence of HTN and CVD outcomes. Dietary sodium and potassium were assessed using a valid and reliable 168-item food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between dietary sodium, potassium and their ratio and risk of outcomes. During the study follow-up, 291 (15.1%) and 79 (5.0%) new cases of HTN and CVD were identified, respectively. No significant association was observed between usual intakes of sodium, potassium and dietary Na/K ratio with the incidence of HTN. There was no significant association between dietary intakes of sodium and potassium per se and the risk of CVD, whereas when dietary sodium to potassium ratio was considered as exposure in the fully-adjusted Cox regression model, and participants in the highest compared to lowest tertile had a significantly increased risk of CVD (HR = 2.19, 95% CI = 1.16-4.14). Our findings suggest that high dietary Na/K ratio could contribute to increased risk of CVD events.


Vessel- and ray-specific monolignol biosynthesis as an approach to engineer fiber-hypolignification and enhanced saccharification in poplar.
Lignin is one of the main factors determining recalcitrance to processing of lignocellulosic biomass towards bio-based materials and fuels. Consequently, wood of plants engineered for low lignin content is typically more amenable to processing. However, lignin-modified plants often exhibit collapsed vessels and associated growth defects. Vessel-specific reintroduction of lignin biosynthesis in dwarfed low-lignin cinnamoyl-CoA reductase1 (ccr1) Arabidopsis mutants using the ProSNBE:AtCCR1 construct overcame the yield penalty while maintaining high saccharification yields, and showed that monolignols can be transported between the different xylem cells acting as 'good neighbors' in Arabidopsis. Here, we translated this research into the bio-energy crop poplar. By expressing ProSNBE:AtCCR1 into CRISPR/Cas9-generated ccr2 poplars, we aimed for vessel-specific lignin biosynthesis to: (i) achieve growth restoration while maintaining high saccharification yields; and (ii) study the existence of 'good neighbors' in poplar wood. Analyzing the resulting ccr2 ProSNBE:AtCCR1 poplars showed that vessels and rays act as good neighbors for lignification in poplar. If sufficient monolignols are produced by these cells, monolignols migrate over multiple cell layers, resulting in a restoration of the lignin amount to wild-type levels. If the supply of monolignols is limited, the monolignols are incorporated into the cell walls of the vessels and rays producing them and their adjoining cells resulting in fiber hypolignification. One such fiber-hypolignified line had 18% less lignin and, despite its small yield penalty, had an increase of up to 71% in sugar release on a plant base upon saccharification.


Dynamic surface site activation: a rate limiting process in electron beam induced etching.
We report a new mechanism that limits the rate of electron beam induced etching (EBIE). Typically, the etch rate is assumed to scale directly with the precursor adsorbate dissociation rate. Here, we show that this is a special case, and that the rate can instead be limited by the concentration of active sites at the surface. Novel etch kinetics are expected if surface sites are activated during EBIE, and observed experimentally using the electron sensitive material ultra nanocrystalline diamond (UNCD). In practice, etch kinetics are of interest because they affect resolution, throughput, proximity effects, and the topography of nanostructures and nanostructured devices fabricated by EBIE.


The contribution of three strong candidate schizophrenia susceptibility genes in demographically distinct populations.
Here we characterize and compare the contribution of three recently identified strong candidate schizophrenia susceptibility genes; G72, neuregulin 1 (NRG1) and dystrobrevin-binding protein 1 (DTNBP1) in two independent datasets of patients with distinct genetic backgrounds. On the basis of corrected P-values from single- and multilocus transmission distortion tests our analysis provides no support for a contribution of G72, NRG1 or DTNBP1 in the tested samples. When transmission of individual haplotypes was considered, a picture more consistent with the original studies emerged, where transmission distortions in the same direction as the original samples and involving the same core haplotypes were observed for G72 and NRG1. Interestingly, whereas the NRG1 gene analysis was dominated by the presence of over-transmitted haplotypes, the G72 gene analysis was consistently dominated in both datasets by under-transmissions. Negative transmissions involved a core haplotype complementary to the originally detected over-transmitted haplotype, suggesting the presence of a protective variant within the G72 locus.


Chronic ethanol feeding increases 7-hydroperoxycholesterol and oxysterols in rat skeletal muscle.
It was our hypothesis that, as a consequence of increased oxidative stress, cholesterol-derived hydroperoxides and oxysterols are increased in skeletal muscles chronically exposed to ethanol. To test this we fed male Wistar rats (0.1 kg initial body weight) a nutritionally complete liquid diet containing ethanol as 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 1(1/2) months, soleus (type I fiber-predominant) and plantaris (type II fiber-predominant) skeletal muscles were dissected out. We measured 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), as well as 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH), and 3 beta-hydroxycholest-5-en-7-one (also termed 7-ketocholesterol; 7-keto). We identified and confirmed by LC-MS the presence of 7 alpha-OOH, 7 beta-OOH and 7 alpha-OH, 7 beta-OH and 7-keto in skeletal muscle of rats. We also showed that in response to chronic alcohol feeding, there were significant increases in soleus 7 alpha-OH (P =.0005), 7 beta-OH (P =.0005), and 7-keto (P =.0007). In the plantaris, mean 7 alpha-OH and 7-keto were not significantly altered (P >.05), but 7 beta-OH increased (P =.0418). This is the first report of 7 alpha-OH, 7 beta-OH, and 7-keto oxysterols being identified in skeletal muscle of rats. Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.


Allometry and Distribution of Nitrogen in Natural Plant Communities of the Tibetan Plateau.
Nitrogen (N) is an important element for most terrestrial ecosystems; its variation among different plant organs, and allocation mechanisms are the basis for the structural stability and functional optimization of natural plant communities. The nature of spatial variations of N and its allocation mechanisms in plants in the Tibetan Plateau-known as the world's third pole-have not been reported on a large scale. In this study, we consistently investigated the N content in different organs of plants in 1564 natural community plots in Tibet Plateau, using a standard spatial-grid sampling setup. On average, the N content was estimated to be 19.21, 4.12, 1.14, and 10.86 mg g-1 in the leaf, branch, trunk, and root, respectively, with small spatial variations. Among organs in communities, leaves were the most active, and had the highest N content, independent of the spatial location; as for vegetation type, communities dominated by herbaceous plants had higher N content than those dominated by woody plants. Furthermore, the allocation of N among different plant organs was allometric, and not significantly influenced by vegetation types and environmental factors; the homeostasis of N was also not affected much by the environment, and varied among the plant organs. In addition, the N allocation strategy within Tibet Plateau for different plant organs was observed to be consistent with that in China. Our findings systematically explore for the first time, the spatial variations in N and allometric mechanisms in natural plant communities in Tibet Plateau and establish a spatial-parameters database to optimize N cycle models.


Separated topologies--a method for relative binding free energy calculations using orientational restraints.
Orientational restraints can improve the efficiency of alchemical free energy calculations, but they are not typically applied in relative binding calculations, which compute the affinity difference been two ligands. Here, we describe a new "separated topologies" method, which computes relative binding free energies using orientational restraints and which has several advantages over existing methods. While standard approaches maintain the initial and final ligand in a shared orientation, the separated topologies approach allows the initial and final ligands to have distinct orientations. This avoids a slowly converging reorientation step in the calculation. The separated topologies approach can also be applied to determine the relative free energies of multiple orientations of the same ligand. We illustrate the approach by calculating the relative binding free energies of two compounds to an engineered site in Cytochrome C Peroxidase.


Brain ascorbic acid and block of the catecholamine synthesis induced by alpha-methyl-tyrosine.
In brain medial-basal areas (midbrain, hypothalamus, striatum) ascorbic acid (AA) content is lower than in the rest of the brain. It has been hypothesized that AA may be involved in brain catecholamine metabolism. To test this hypothesis AA content in medial-basal areas and in the remaining brain areas was measured in rats pretreated with alpha-methyl-paratyrosine (alpha-MpT), a tyrosine hydroxylase inhibitor. The AA content, in brain medial-basal areas, had slightly decreased, without statistically significant differences, in rats treated with alpha-MpT in comparison with untreated animals. Therefore the role of AA in brain metabolism is not clear to.


A Review of Apps for Calming, Relaxation, and Mindfulness Interventions for Pediatric Palliative Care Patients.
Patients and families increasingly use mobile apps as a relaxation and distraction intervention for children with complex, chronic medical conditions in the waiting room setting or during inpatient hospitalizations; and yet, there is limited data on app quality assessment or review of these apps for level of engagement, functionality, aesthetics, or applicability for palliative pediatric patients. The pediatric palliative care study team searched smartphone application platforms for apps relevant to calming, relaxation, and mindfulness for pediatric and adolescent patients. Apps were reviewed using a systematic data extraction tool. Validated Mobile Application Rating Scale (MARS) scores were determined by two blinded reviewers. Apps were then characterized by infant, child, adolescent, and adult caregiver group categories. Reviewer discussion resulted in consensus. Sixteen of the 22 apps identified were included in the final analysis. The apps operated on either iOS or Android platforms. All were available in English with four available in Spanish. Apps featured a relaxation approach (12/16), soothing images (8/16), and breathing techniques (8/16). Mood and sleep patterns were the main symptoms targeted by apps. Provision of mobile apps resource summary has the potential to foster pediatric palliative care providers' knowledge of app functionality and applicability as part of ongoing patient care.


The maleness of larger angiosperm flowers.
Flower biomass varies widely across the angiosperms. Each plant species invests a given amount of biomass to construct its sex organs. A comparative understanding of how this limited resource is partitioned among primary (male and female structures) and secondary (petals and sepals) sexual organs on hermaphrodite species can shed light on general evolutionary processes behind flower evolution. Here, we use allometries relating different flower biomass components across species to test the existence of broad allocation patterns across the angiosperms. Based on a global dataset with flower biomass spanning five orders of magnitude, we show that heavier angiosperm flowers tend to be male-biased and invest strongly in petals to promote pollen export, while lighter flowers tend to be female-biased and invest more in sepals to insure their own seed set. This result demonstrates that larger flowers are not simple carbon copies of small ones, indicating that sexual selection via male-male competition is an important driver of flower biomass evolution and sex allocation strategies across angiosperms.


The cost-effectiveness of weekly epoetin alfa relative to weekly darbepoetin alfa in patients with chemotherapy-induced anemia.
To compare the cost-effectiveness of epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of chemotherapy-induced anemia (CIA), using dosing regimens approved by the FDA (EPO 40,000 U once weekly and DARB 2.25 U once weekly and DARB 2.25 mcg/kg once weekly). The study compared published results of two double-blind, randomized, phase III trials one utilizing EPO (N = 166) and the other, DARB (N = 367). Patients in both trials similar baseline characteristics. Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated (i.e., did not require blood transfusion) during weeks 0-16 and 5-16, respectively. Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost (WAC) and average drug utilization over 16 weeks. Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness. Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs. Estimated drug costs over 16 weeks were $9,039 for EPO and $13,555 for DARB. During weeks 5-16, 85% of EPO patients and 73% of DARB patients were successfully treated, resulting in average cost-effectiveness ratios of $106 for EPO and $186 for DARB per one per cent of successfully treated patients. A 33% reduction in DARB WAC was required to achieve the same drug costs as for EPO. Utilizing FDA-approved doses, EPO was found to result in lower drug costs and better treatment success when compared to DARB. Hence, EPO is a dominant alternative compared to DARB for the treatment of CIA. The analyses presented here are not without limitations. Specifically, although the studies were comparable, patients were ultimately drawn from different populations.


biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial.
To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis. Multicentre three-arm randomised controlled trial. UK NHS hospitals. Hospitalised critically ill adults who have been commenced on intravenous antibiotics for sepsis. Three protocols for guiding antibiotic discontinuation will be compared: (a) standard care; (b) standard care + daily CRP monitoring; (c) standard care + daily PCT monitoring. Standard care will be based on routine sepsis management and antibiotic stewardship. Measurement of outcomes and costs. Outcomes will be assessed to 28 days. The primary outcomes are total duration of antibiotics and safety outcome of all-cause mortality. Secondary outcomes include: escalation of care/re-admission; infection re-lapse/recurrence; antibiotic dose; length and level of critical care stay and length of hospital stay. Ninety-day all-cause mortality rates will also be collected. An assessment of cost effectiveness will be performed. In the setting of routine NHS care, if this trial finds that a treatment protocol based on monitoring CRP or PCT safely allows a reduction in duration of antibiotic therapy, and is cost effective, then this has the potential to change clinical practice for critically ill patients with sepsis. Moreover, if a biomarker-guided protocol is not found to be effective, then it will be important to avoid its use in sepsis and prevent ineffective technology becoming widely adopted in clinical practice.


Western Analysis of Histone Modifications (Aspergillus nidulans).
Western blotting allows for the specific detection of proteins and/or modifications of proteins by an antibody of interest. This protocol utilizes a crude nuclei extraction protocol for Aspergillus nidulans to enrich for histones and other nuclear proteins prior to gel electrophoresis. Post translational modifications of histones may then be easily detected. After electrophoresis, the selected antibodies are used to detect and quantify levels of the modifications of interest.


Fetal surveillance.
The primary objective of fetal surveillance is to prevent antenatal fetal deaths, which still account for greater than one half of perinatal mortality. Several techniques for assessing fetal well-being are available to the practicing obstetrician, including fetal movement counting, nonstress testing, contraction stress testing, fetal biophysical assessment with real-time sonography, and Doppler ultrasonography for measuring umbilical and fetal blood flow. Despite several unanswered questions regarding fetal surveillance, identification of high-risk pregnancies allows appropriate fetal evaluation that can reduce intrauterine fetal death rates.


Diagnostic reliability of pediatric appendicitis score, ultrasound and low-dose computed tomography scan in children with suspected acute appendicitis.
Diagnosis of appendicitis in children is clinically challenging. Computed tomography (CT) is the gold standard for diagnosis; however, radiation exposure early in life is a concern with this technique. Therefore, in this study, we aimed to evaluate the diagnostic reliability of low-dose CT, pediatric appendicitis score (PAS), and abdominal ultrasound (US) in children with acute appendicitis, to reach a safe diagnosis. This retrospective study was conducted on 140 children who were admitted with clinically suspected acute appendicitis (45 with positive appendicitis and 95 children with negative appendicitis). Low-dose CT was performed, and PAS was retrospectively calculated for all subjects. US was initially performed for 38 subjects. All results were compared with the final diagnosis reached by an operative, histopathological analysis and follow-up. Low-dose CT showed a sensitivity, specificity, and accuracy of 97.8%, 100%, and 99.3%, respectively. At a cutoff value ≥5, PAS showed a sensitivity, specificity, and accuracy of 95%, 84%, and 89%, respectively. Abdominal US examination showed sensitivity, specificity, and accuracy of 55.6%, 85%, and 71%, respectively. Implementing Poortman's model resulted in higher accuracy (92%) of US. There was a significant difference in accuracy between a low-dose CT and PAS on one side and between Poortman's model and US examination on the other side. A diagnostic scheme was suggested using PAS as the excluding tool (PAS ≤2 send home and ≥7 send directly to operation) followed by US examination and reserving low-dose CT for inconclusive cases. This scheme would eliminate the use of CT for at least 33.7% and in 7 cases who had initial US examination. Although CT remains the most accurate and less operator-dependent diagnostic tool for pediatric appendicitis, the radiation hazards could however be minimized using PAS as an excluding tool and US as the primary imaging modality followed by low-dose CT for inconclusive cases only.


Effect of disodium cromoglycate on ventilation and gas exchange during exercise in asthmatic children with a postexertion FEV1 fall less than 15 percent.
The purpose of this study is to evaluate the effect of disodium cromoglycate (DSCG) on gas exchange and ventilation during incremental exercise in asthmatic children with an FEV1 fall less than 15 percent from the baseline after the exercise. Seventeen children (aged 8 to 14 years) with a history of mild to moderate asthma but no clinical and spirometric evidence of exercise-induced asthma (EIA) underwent two maximal exercise tests in a randomized order: test A without premidication and test B after inhalation of DSCG, 40 mg. To evaluate the effect of DSCG on normal airways, nine healthy children performed the same exercise protocol. Pulmonary function was normal at rest and after treadmill exercise test (the mean postexercise fall in FEV1 was 5.9 percent in test A and 1.5 percent in test B). Gas exchange, minute ventilation (VE) and heart rate (HR) were monitored during running in both tests. In the asthmatic subjects, there were no differences in oxygen uptake (VO2), carbon dioxide output (VCO2), and VE at rest between the two tests. During exercise, VE, VO2, VCO2, and energy cost (EC[O2 ml.kg-1.m-1]) of running in the asthmatic subjects were significantly lower in test B than in test A (analysis of variance, p < 0.01) for comparable work rates. Maximal minute ventilation (VEmax) was significantly higher in test A (46.9 +/- 14.6[+/- SD]L.min-1) than in test B (43.2 +/- 14 L. min-1; p < 0.05). We found no significant effect of DSCG on gas exchange and ventilation during exercise in the healthy children (VEmax 47.8 +/- 25 and 48.4 +/- 25 L.min-1 in test A and B, respectively). In conclusion, premedication with DSCG appears to decrease the ventilatory cost of exercise in asthmatic children who do not present a substantial fall in FEV1 after an exercise test without pretreatment.


Prevalence of cigarette smoking among young adults in Pakistan.
To obtain information about the prevalence of cigarette smoking among a selected sample of university students in Karachi and build our understanding of the determinants of smoking with respect to family smoking, smoking in the home, smoke-free public places, and quit smoking cessation programmes. Data were collected as a part of a pilot project initiated by Jinnah University Karachi. Participants were 629 university students (432 males and 197 females) aged 18-25 years from ten universities in Karachi. Descriptive statistics and Logistic regression analyses were used to determine the results and conclusions. Thirty-nine per cent of students had smoked a whole cigarette in their life time, whereas 25% had smoked 100 or more cigarettes in their lifetime. Overall, 23% of students (31% male and 6% female) were classified as a current smoker and their mean age and standard deviation of smoking initiation was 17 +/- 2.7 years (17 +/- 2.6) for males and 16 +/- 2.9 females. Sixty-three percent of smokers reported that public places should be smoke-free. Logistic regression analyses adjusted by age and gender suggested that parental and sibling influence and number of close friends and individuals who smoke at home were highly predictive of being a smoker. Findings from this study suggest that student were generally open to smoking cessation treatment and no-smoking restrictions.


F/Cl-exchange on AlCl(3)-pyridine adducts: synthesis and characterization of trans-difluoro-tetrakis-pyridine-aluminum-chloride, [AlF2(Py)4]+Cl-.
Whereas liquid CCl3F reacts with solid AlCl3 exothermically under chlorine-fluorine-exchange already above -20 degrees C, no reaction takes place between CCl3F and the pyridine complexes of AlCl3 (AlCl3.Py, AlCl3.2Py, or AlCl3.3Py) up to 100 degrees C. The desired chlorine by fluorine substitution on the monomer AlCl3-pyridine adducts occurs, however, easily using Me3SiF as fluorinating agent. By reacting AlCl3.3Py with Me3SiF (even up to 10-fold stoichiometric excess) in pyridine as a solvent, only two of the three Cl atoms can be substituted by fluorine, leading in good yield to the new "mixed aluminum halide", AlF2Cl.4Py. Actually, it represents the first example of a stable solid donor-acceptor adduct of an aluminum-III halide with two different halogens of defined stoichiometry. It was characterized by multinuclear solid-state NMR (27Al and 19F), IR spectroscopy, as well as single-crystal structure analysis. The new compound has an ionic solid-state structure with helical trans-octahedral [(Py)4AlF2]+ cations and isolated Cl- anions. The comparison of its 27Al MAS solid-state NMR spectra with those of a compound bearing the analogous [(Py)4AlCl2]+ cation reveals an extreme increase in the quadrupolar coupling constants, from 0.24 MHz in case of the chlorine cation to about 16 MHz in case of the new [(Py)4AlF2]+ cation.


Interaction of tRNAs and of phosphorothioate-substituted nucleic acids with an organomercurial. Probing the chemical environment of thiolated residues by affinity electrophoresis.
The interactions of 4-thiouridine and 5-[(methylamino)methyl]-2-thiouridine in tRNA and of phosphorothioate esters in nucleic acids with an organomercurial have been investigated. For this purpose, an affinity electrophoretic system has been developed in which the mercury derivative has been covalently immobilized in a standard polyacrylamide gel. The retardation of thiolated macromolecules was found to be sensitive to the chemical environment of the sulfur atom, giving characteristic interaction constants dependent on the nature of the modification and its accessibility to binding. The interaction could, in the case of tRNA, be abolished by conventional specific chemical modification of the thiolated bases, as well as by irradiation with 32P-derived beta-emission. Not only has the fractionation of sulfur-modified from unmodified species been attained but a quantitative application of the technique has made it possible to study the binding of mercury and, by competition, that of magnesium in terms of the conformation of tRNA.


Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most lethal cancers worldwide. Several basic studies have confirmed that Kirsten rat sarcoma virus (KRAS) is a key driver gene for the occurrence of PDAC, and KRAS mutations have also been found in most patients in clinical studies. In this study, two pan-KRAS inhibitors, BI-2852 and BAY-293, were chosen as chemical probes to investigate their antitumor potency in PDAC. Their inhibitory effects on KRAS activation were validated in vitro and their antiproliferative potency in PDAC cell lines were profiled, with half-maximal inhibitory concentration (IC50) values of approximately 1 μM, demonstrating the therapeutic potential of pan-KRAS inhibitors in the treatment of PDAC. However, feedback regulation in the KRAS pathway weakened inhibitor activity, which was observed by a 50 times difference in BAY-293 from in vitro activity. Furthermore, pan-KRAS inhibitors effectively inhibited cell proliferation in 3D organoids cultured from PDAC patient samples; however, there were some variations between individuals. These results provide a sufficient theoretical foundation for KRAS as a clinical therapeutic target and for the application of pan-KRAS inhibitors in the treatment of PDAC, with important scientific significance in translational medicine.


Effects of pentoxifylline on differentiation, maturation, and function of human CD14+ monocyte-derived dendritic cells.
Pentoxifylline (PTX) is a nonspecific phosphodiesterase inhibitor which has potent immunoregulatory and antiinflammatory effects. Although its immunomodulation property has been recognized, it is not clear whether PTX could affect dendritic cells (DCs), the most efficient antigen-presenting cells. The purpose of this study was to determine whether PTX could suppress DC differentiation, maturation, and its associated functions. Immature DCs (iDCs) were generated from human peripheral blood mononuclear cell CD14+ monocytes cultured with granulocyte macrophage colony stimulating factor and interleukin-4 for 5 days. PTX concentration-dependently suppressed the expression of iDC differentiation markers including CD54, CD80, CD86, and human leukocyte antigen-DR. In addition, PTX also inhibited DC maturation marker CD83 expression after stimulating DCs with lipopolysaccharide. Furthermore, PTX inhibited the antigen-uptake ability of DCs when tested by fluorescein isothiocyanate-dextran endocytosis assay. PTX significantly reduced the production of TNF-alpha and IFN-gamma in mature DCs (mDCs). Consequently, PTX-treated mDCs showed a reduced activity of mDC-induced T-cell allostimulation and proliferation by mixed-lymphocyte reaction (MLR) assay. Therefore, PTX significantly inhibits CD14+ monocyte-derived DC differentiation, maturation, antigen-uptake ability of iDCs, and antigen-presentation ability of mDCs possibly due to the suppression of TNF-alpha and IFN-gamma production. These results suggested that inhibitory effects of PTX on DCs may contribute its antiinflammatory and immunoregulatory functions.


Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects.
This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration-time curves (AUC∞ ) and maximum concentrations (Cmax ) as follows: bupropion, AUC∞ reduced 42%, Cmax reduced 31%; repaglinide, AUC∞ reduced 8%, Cmax reduced 14%; caffeine, AUC∞ increased 4%, Cmax reduced 1%; dextromethorphan, AUC∞ increased 18%, Cmax increased 17%; R-methadone, AUC∞ reduced 10%, Cmax increased 3%; S-methadone, AUC∞ reduced 35%, Cmax increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2-, CYP2C8-, or CYP2D6-mediated metabolism.


Evolution of immune reactions.
The history and evolutionary pathways of defense reactions among various forms of life are reconstructed. The vertebrates evolved step-by-step from their invertebrate ancestors living in the distant past. The ancestry of vertebrate defense mechanisms must be traceable to them because these functions cannot be considered separately from the common evolutionary schema. The first part of this survey is therefore devoted to the description of major defense reactions and achievements in invertebrates. Particular emphasis is given to the taxa of present-day invertebrates most likely to exhibit some relationship to the chordates and thus to show real traces of vertebrate immune patterns. The second part involves three key assemblages of deuterostomate animals--the echinoderms, the nonvertebrate chordates, and the first vertebrates because these animals are believed to have created the prerequisites for transition from the invertebrate type of defense to the vertebrate type of adaptive immunity.


The C-terminal region of translesion synthesis DNA polymerase η is partially unstructured and has high conformational flexibility.
Eukaryotic DNA polymerase η catalyzes translesion synthesis of thymine dimers and 8-oxoguanines. It is comprised of a polymerase domain and a C-terminal region, both of which are required for its biological function. The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region contains a ubiquitin-binding/zinc-binding (UBZ) motif and a PCNA-interacting protein (PIP) motif. Currently little structural information is available for this region of polymerase η. Using a combination of approaches-including genetic complementation assays, X-ray crystallography, Langevin dynamics simulations, and small-angle X-ray scattering-we show that the C-terminal region is partially unstructured and has high conformational flexibility. This implies that the C-terminal region acts as a flexible tether linking the polymerase domain to PCNA thereby increasing its local concentration. Such tethering would facilitate the sampling of translesion synthesis polymerases to ensure that the most appropriate one is selected to bypass the lesion.


[Determination of serum highly sensitive C-reactive protein in patients with type 2 diabetes].
To investigate the relationship between serum level of highly sensitive C-reactive protein (hs-CRP) and insulin sensitivity in type 2 diabetic patients. Serum hs-CRP level was determined by highly sensitive enzyme-linked immunosorbent assay (ELISA) in 65 patients with type 2 diabetes and 25 normal controls. Plasma glucose, serum insulin, glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (UAER), plasma lipids and lipoprotein were also measured. Moreover, homeostasis model analysis (HOMA) of insulin resistance index (HOMA-IR) and islet secretion index (HOMA-IS) were calculated to estimate the insulin sensitivity and islet function. In the patients with type 2 diabetes, serum hs-CRP was increased, HOMA-IR index and HOMA-IS index were decreased as compared with the normal control subjects (P<0.01). Moreover, serum hs-CRP was significantly higher in poorly controlled diabetic patients (n=23) with HbA1c >7% than that in well controlled diabetic patients (n=42) with HbA1c<7%. Liner regression analysis in diabetic patients showed that serum hs-CRP was negatively correlated with HOMA-IS index but positively correlated with fasting plasma glucose, body mass index, HbA1c and diastolic blood pressure, respectively. Serum HS-CRP level is higher in the patients with type 2 diabetes than in normal subjects, and plays an role in the development and progression of type 2 diabetes mellitus.


Simulation of in vivo dynamics during robot assisted joint movement.
Robots are very useful tools in orthopedic research. They can provide force/torque controlled specimen motion with high repeatability and precision. A method to analyze dissipative energy outcome in an entire joint was developed in our group. In a previous study, a sheep knee was flexed while axial load remained constant during the measurement of dissipated energy. We intend to apply this method for the investigation of osteoarthritis. Additionally, the method should be improved by simulation of in vivo knee dynamics. Thus, a new biomechanical testing tool will be developed for analyzing in vitro joint properties after different treatments. Discretization of passive knee flexion was used to construct a complex flexion movement by a robot and simulate altering axial load similar to in vivo sheep knee dynamics described in a previous experimental study. The robot applied an in vivo like axial force profile with high reproducibility during the corresponding knee flexion (total standard deviation of 0.025 body weight (BW)). A total residual error between the in vivo and simulated axial force was 0.16 BW. Posterior-anterior and medio-lateral forces were detected by the robot as a backlash of joint structures. Their curve forms were similar to curve forms of corresponding in vivo measured forces, but in contrast to the axial force, they showed higher total standard deviation of 0.118 and 0.203 BW and higher total residual error of 0.79 and 0.21 BW for posterior-anterior and medio-lateral forces respectively. We developed and evaluated an algorithm for the robotic simulation of complex in vivo joint dynamics using a joint specimen. This should be a new biomechanical testing tool for analyzing joint properties after different treatments.


Parasites, diseases and health status of sympatric populations of sambar deer and white-tailed deer in Florida.
From December 1983 to December 1984 a study on parasites, diseases and health status was conducted on sympatric populations of sambar deer (Cervus unicolor) and white-tailed deer (Odocoileus virginianus) from St. Vincent Island, Franklin County, Florida. Ten sambar and six white-tailed deer were examined. White-tailed deer had antibodies to epizootic hemorrhagic disease virus and bluetongue virus. Serologic tests for antibodies to the etiologic agents of bovine virus diarrhea, infectious bovine rhinotracheitis, vesicular stomatitis, parainfluenza 3, brucellosis, and leptospirosis were negative in both species of deer. White-tailed deer harbored 19 species of parasites; all were typical of the parasite fauna of this species in coastal regions of the southeastern United States. Sambar deer harbored 13 species of parasites, which apparently were derived largely from white-tailed deer. The only exception was Dermacentor variabilis which occurs frequently on wild swine on the island. The general health status of sambar deer appeared to be better than that of white-tailed deer. This was hypothesized to result from the sambar deer's utilization of food resources unavailable or unacceptable to white-tailed deer and to the absence and/or lower frequency of certain pathogens in sambar deer.


Behavior of pure gallium in water and various saline solutions.
This study investigated the chemical stability of pure gallium in water and saline solutions in order to obtain fundamental knowledge about the corrosion mechanism of gallium-based alloys. A pure gallium plate (99.999%) was suspended in 50 mL of deionized water, 0.01%, 0.1% or 1% NaCl solution at 24 +/- 2 degrees C for 1, 7, or 28 days. The amounts of gallium released into the solutions were determined by atomic absorption spectrophotometry. The surfaces of the specimens were examined after immersion by x-ray diffractometry (XRD) and x-ray photoelectron spectroscopy (XPS). In the solutions containing 0.1% or more NaCl, the release of gallium ions into the solution was lowered when compared to deionized water after 28-day immersion. Gallium oxide monohydroxide was found by XRD on the specimens immersed in deionized water after 28-day immersion. XPS indicated the formation of gallium oxide/hydroxide on the specimens immersed in water or 0.01% NaCl solution. The chemical stability of pure solid gallium was strongly affected by the presence of Cl- ions in the aqueous solution.


Practical screening procedure for chloramphenicol in milk at low parts per billion level.
A relatively simple screening procedure for the detection of chloramphenicol in cow's milk is detailed. The drug in 50 mL skim milk is adsorbed onto Chromosorb 102 and subsequently eluted; interfering impurities are removed by passing the effluent directly over one column containing small beds of alumina and cation exchange resin in the H+ form. After solvent is removed, the nitro group of the drug is reduced with zinc dust in HCl, and the drug is detected by diazotization and coupling to N-1-(naphthyl)ethylenediamine. Milk containing greater than or equal to 4 ppb chloramphenicol can be detected. A number of antibiotics and sulfa drugs permitted for use with dairy cows do not interfere with chloramphenicol detection, nor do some naturally occurring aromatic amino compounds. Nitromide (3,5-dinitrobenzamide) will interfere. It is estimated that approximately 50 samples of skimmed milk can be screened by one person during the working day. Cows secreted the drug into their milk for approximately 3 days following injection of chloramphenicol either intramuscularly or via infusion into the udder.


Life cycle assessment of an advanced bioethanol technology in the perspective of constrained biomass availability.
Among the existing environmental assessments of bioethanol, the studies suggesting an environmental benefit of bioethanol all ignore the constraints on the availability of biomass resources and the implications competition for biomass has on the assessment We show that toward 2030, regardless of whether a global or European perspective is applied, the amount of biomass, which can become available for bioethanol or other energy uses, will be physically and economically constrained. This implies that use of biomass or land for bioethanol production will most likely happen at the expense of alternative uses. In this perspective, we show that for the case of a new advanced bioethanol technology, in terms of reducing greenhouse emissions and fossil fuel dependency, more is lost than gained when prioritizing biomass or land for bioethanol. Technology pathways involving heat and power production and/or biogas, natural gas or electricity for transport are advantageous.


Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.
Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.


Insulin and 20-hydroxyecdysone oppose each other in the regulation of phosphoinositide-dependent kinase-1 expression during insect pupation.
Insulin promotes larval growth of insects by stimulating the synthesis of the steroid hormone 20-hydroxyecdysone (20E), which induces pupation and apoptosis. However, the mechanism underlying the coordinate regulation of insect pupation and apoptosis by these two functionally opposing hormones is still unclear. Here, using the lepidopteran insect and serious agricultural pest Helicoverpa armigera (cotton bollworm) as a model, we report that phosphoinositide-dependent kinase-1 (PDK1) and forkhead box O (FoxO) play key roles in these processes. We found that the transcript levels of the PDK1 gene are increased during the larval feeding stages. Moreover, PDK1 expression was increased by insulin, but repressed by 20E. dsRNA-mediated PDK1 knockdown in the H. armigera larvae delayed pupation and resulted in small pupae and also decreased Akt/protein kinase B expression and increased FoxO expression. Furthermore, the PDK1 knockdown blocked midgut remodeling and decreased 20E levels in the larvae. Of note, injecting larvae with 20E overcame the effect of the PDK1 knockdown and restored midgut remodeling. FoxO overexpression in an H. armigera epidermal cell line (HaEpi) did not induce apoptosis, but promoted autophagy and repressed cell proliferation. These results reveal cross-talk between insulin and 20E and that both hormones oppose each other's activities in the regulation of insect pupation and apoptosis by controlling PDK1 expression and, in turn, FoxO expression. We conclude that sufficiently high 20E levels are a key factor for inducing apoptosis during insect pupation.


Exploiting an allosteric binding site of PRMT3 yields potent and selective inhibitors.
Protein arginine methyltransferases (PRMTs) play an important role in diverse biological processes. Among the nine known human PRMTs, PRMT3 has been implicated in ribosomal biosynthesis via asymmetric dimethylation of the 40S ribosomal protein S2 and in cancer via interaction with the DAL-1 tumor suppressor protein. However, few selective inhibitors of PRMTs have been discovered. We recently disclosed the first selective PRMT3 inhibitor, which occupies a novel allosteric binding site and is noncompetitive with both the peptide substrate and cofactor. Here we report comprehensive structure-activity relationship studies of this series, which resulted in the discovery of multiple PRMT3 inhibitors with submicromolar potencies. An X-ray crystal structure of compound 14u in complex with PRMT3 confirmed that this inhibitor occupied the same allosteric binding site as our initial lead compound. These studies provide the first experimental evidence that potent and selective inhibitors can be created by exploiting the allosteric binding site of PRMT3.


Vero cells as a model to study the effects of adenoviral gene delivery vectors on the RNAi system in context of viral infection.
Technology based on RNA interference (RNAi) is a promising source for new antiviral therapies. Although the application of RNAi has been studied extensively, significant problems with using RNAi remain. Very few studies have specifically assessed model systems for testing the effects of viruses or gene delivery vectors on the RNAi system. Since viruses have developed efficient strategies to circumvent the interferon (IFN) response, an IFN-deficient model system should be considered. Here we show that in Vero cells, which lack IFN-alpha and IFN-beta genes, knockdown of Dicer, a key RNAi component, led to accelerated death of cells infected with other evolutionary distinct viruses: influenza A virus, vesicular stomatitis virus and poliovirus. We also demonstrate that transduction of Vero cells with adenoviral vector with subsequent infection with influenza A virus also resulted in increased mortality of infected cells. These effects were much weaker in IFN-producing A549 and Hela cell lines. Thus, the Vero cell line could serve as an interesting model for studying the effects of gene delivery vectors on the RNAi system in the context of virus-related disorders.


Prospective Associations between Religiousness/Spirituality and Depression and Mediating Effects of Forgiveness in a Nationally Representative Sample of United States Adults.
The present investigation examines the prospective associations of religiousness/spirituality with depression and the extent to which various dimensions of forgiveness act as mediating mechanisms of these associations. Data are from a nationally representative sample of United States adults who were first interviewed in 1998 and reinterviewed six months later. Measures of religiousness/spirituality, forgiveness, and various sociodemographics were collected. Depression was assessed using the Composite International Diagnostic Interview administered by trained interviewers. Results showed that religiousness/spirituality, forgiveness of oneself and others, and feeling forgiven by God were associated, both cross-sectionally and longitudinally, with depressive status. After controlling for initial depressive status, only forgiveness of oneself and others remained statistically significant predictors of depression. Path analyses revealed that religiousness/spirituality conveyed protective effects, prospectively, on depression by way of an indirect path through forgiveness of others but not forgiveness of oneself. Hence, forgiveness of others acts as a mechanism of the salutary effect of religiousness/spirituality, but forgiveness of oneself is an independent predictor. Conclusions regarding the continued development of this type of research and for the treatment of clients with depression are offered.


Enhanced Pitch Discrimination for Cochlear Implant Users with a New Haptic Neuroprosthetic.
The cochlear implant (CI) is the most widely used neuroprosthesis, recovering hearing for more than half a million severely-to-profoundly hearing-impaired people. However, CIs still have significant limitations, with users having severely impaired pitch perception. Pitch is critical to speech understanding (particularly in noise), to separating different sounds in complex acoustic environments, and to music enjoyment. In recent decades, researchers have attempted to overcome shortcomings in CIs by improving implant technology and surgical techniques, but with limited success. In the current study, we take a new approach of providing missing pitch information through haptic stimulation on the forearm, using our new mosaicOne_B device. The mosaicOne_B extracts pitch information in real-time and presents it via 12 motors that are arranged in ascending pitch along the forearm, with each motor representing a different pitch. In normal-hearing subjects listening to CI simulated audio, we showed that participants were able to discriminate pitch differences at a similar performance level to that achieved by normal-hearing listeners. Furthermore, the device was shown to be highly robust to background noise. This enhanced pitch discrimination has the potential to significantly improve music perception, speech recognition, and speech prosody perception in CI users.


SISSY: An efficient and automatic algorithm for the analysis of EEG sources based on structured sparsity.
Over the past decades, a multitude of different brain source imaging algorithms have been developed to identify the neural generators underlying the surface electroencephalography measurements. While most of these techniques focus on determining the source positions, only a small number of recently developed algorithms provides an indication of the spatial extent of the distributed sources. In a recent comparison of brain source imaging approaches, the VB-SCCD algorithm has been shown to be one of the most promising algorithms among these methods. However, this technique suffers from several problems: it leads to amplitude-biased source estimates, it has difficulties in separating close sources, and it has a high computational complexity due to its implementation using second order cone programming. To overcome these problems, we propose to include an additional regularization term that imposes sparsity in the original source domain and to solve the resulting optimization problem using the alternating direction method of multipliers. Furthermore, we show that the algorithm yields more robust solutions by taking into account the temporal structure of the data. We also propose a new method to automatically threshold the estimated source distribution, which permits to delineate the active brain regions. The new algorithm, called Source Imaging based on Structured Sparsity (SISSY), is analyzed by means of realistic computer simulations and is validated on the clinical data of four patients.


Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase.
Gamma-secretase is the second of two proteolytic enzymes responsible for the release of the amyloid beta-peptide implicated in the etiology of Alzheimer's disease. Here, we used solid-phase synthesis to generate a new series of helical peptides as gamma-secretase inhibitors, one of which, 11, showed an IC(50) of 140 pM in a cell-free enzyme assay.


Correlation of beta-2-microglobulin concentration changes to changes of distribution volume.
Plasma and ultrafiltrate beta-2-microglobulin (B2M) concentrations were determined during hemofiltration (HF) and hemodialysis (HD) in order to evaluate elimination kinetics of B2M. Calculations were done on the basis of plasma-water-concentrations (PWC). Elimination of B2M during HF follows first order kinetics (r = 0.97) and the volume of B2M distribution was calculated to be 17 +/- 2% of body weight. This reflects extracellular volume (ECV). Changes of ECV in HD were induced by weight loss and further provoked by fluid shifts from intra- to extracellular volume and vice versa induced by varying dialysate sodium concentration. These ECV changes were followed by determining inuline in plasma and total dialysate. Changes of B2M concentration correlate well to changes of ECV (r = 0.98). Thus intratreatment concentration changes of B2M in cuprophane dialysis reflect simultaneous changes of B2M distribution volume. This does not exclude the possibility of B2M generation stimulated by dialysis, but proving such effects in vivo will be difficult because of multiple variants, that must be controlled.


Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in patients with pneumonia due to the SARS coronavirus.
By using a recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein-based enzyme-linked immunosorbent assay (ELISA) and serum specimens serially collected (from day 0 to day 240 after symptom onset) from patients with pneumonia due to SARS-CoV, we analyzed the longitudinal profiles of immunoglobulin G (IgG), IgM, and IgA antibodies against the SARS-CoV nucleocapsid protein in patients with pneumonia due to SARS-CoV. For IgG, the median optical density at 450 nm (OD450) turned positive at day 17 and a biphasic response was observed. At day 240, all patients were still positive for anti-nucleocapsid protein IgG antibody. For IgM, the median OD450 turned positive at day 20.5, peaked at about day 80, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgM antibody. For IgA, the median OD450 turned positive at day 17, peaked at about day 50, and fell to below the baseline level at about day 180. At day 240, 36% of the patients were still positive for anti-nucleocapsid protein IgA antibody. The time of seroconversion detected by the recombinant SARS-CoV nucleocapsid protein-based ELISA and that detected by indirect immunofluorescence assay were similar. The median times of seroconversion for IgG, IgM, and IgA detected by the indirect immunofluorescence assay were 17 days (17 days by ELISA), 16.5 days (20.5 days by ELISA), and 17.5 days (17 days by ELISA), respectively, after disease onset. One, four, and one of the six patients who died did not produce any IgG, IgM, and IgA antibodies against the nucleocapsid protein of SARS-CoV, respectively, although these antibodies were detected in all six patients by the indirect immunofluorescence assay. Further studies should be performed to see whether SARS-CoV nucleocapsid protein antibody positivity has any prognostic significance.


Postnatal glucocorticoid use impacts renal function in VLBW neonates.
Preterm neonates often require glucocorticoids to manage refractory hypotension, prevent, and treat bronchopulmonary dysplasia. We have investigated the effect of cumulative dose and duration of glucocorticoids on blood pressure and renal function in VLBW infants. In this retrospective cohort study, medical records of infants (GA ≤ 35 weeks) born January 2015 to December 2019 were reviewed to extract demographic and clinical characteristics, dose and duration of steroids, blood pressure (BP), and creatinine at the time of discharge from the neonatal intensive care unit. Two hundred and eighty-three neonates with average GA (28 ± 3 weeks) and birthweight (1060±381 g). Twenty-eight percent (33/116) of infants who received postnatal steroids developed hypertension versus 16% (27/167) of controls (OR = 2.0, p = 0.011). There was a correlation between the cumulative dosage of postnatal steroids and systolic BP (R2 = 0.06, p < 0.001). With increasing steroid dose and total steroid days, there was a significant increase in creatinine clearance at the time of discharge (R2 = 0.13, p < 0.001; R2 = 0.13, p < 0.001, respectively). Cumulative dose of postnatal steroids and duration of use is associated with increased systolic BP in premature infants. Postnatal steroids should be used prudently to prevent long-term cardiovascular and renal morbidity. Preterm neonates are exposed to a high dose of glucocorticoids during their neonatal intensive care stay. The dose and duration of use of postnatal glucocorticoids was associated with significant increase in blood pressure at the time of discharge in preterm neonates. Postnatal glucocorticoid use is associated with improved creatinine clearance likely due to a state of hyperfiltration and may lead to chronic kidney disease later in life. Postnatal glucocorticoids should be used prudently in this highly vulnerable population.


Incremental effectiveness of second dose varicella vaccination for outbreak control at an elementary school in Philadelphia, pennsylvania, 2006.
In 2006, the Philadelphia Department of Public Health conducted an investigation of a varicella outbreak at an elementary school in which second-dose vaccination for outbreak control (VOC) was implemented. We evaluated the effectiveness of this intervention. Self-administered questionnaires collected varicella disease and vaccination information. Students eligible for second-dose VOC were 1-dose vaccine recipients without prior varicella disease. A breakthrough varicella case was defined as a maculopapulovesicular rash in a student with onset >42 days after 1-dose vaccination without other apparent cause. Vaccine effectiveness was evaluated using survival analysis techniques and analyzed by vaccine status (first dose versus second dose). Multivariable Cox proportional hazard models were used to identify statistical interactions and adjust for confounders. The questionnaire response rate was 92% (342/370). Of the 286 eligible students, 187 (65%) received a second-dose VOC. The crude attack rate was 9/187 (5%) among second-dose VOC recipients; 43/99 (43%) among 1-dose recipients, and 5/6 (83%) among unvaccinated students. Second-dose VOC recipients had milder rashes, compared with 1-dose or unvaccinated students. The adjusted incremental second-dose vaccine effectiveness was 76% (95% confidence interval: 44%-90%) for students with classroom exposure. Incremental effectiveness was similar (79%) when we extended the immune response time from 4 days to 7 days after second-dose VOC. Second-dose VOC resulted in a substantial reduction in varicella incidence for students with classroom exposure. Until high rates of routine second-dose vaccine coverage are achieved, clinicians should consider second-dose VOC an appropriate intervention to reduce disease transmission in institution-based outbreaks.


[Effect of prostaglandin E1 on the systemic and regional hemodynamics of dogs].
The effect of prostaglandin E1 (PGE1) on the cardiovascular system of the dog has been studied in experiments with anesthetized dogs. After intravenous injections of PGE1 (5 microgram/kg) arterial hypotension, tachycardia, increase of cardiac output, increase of myocardial contractility were observed. PGE1 induced dilatation of pulmonary vessels. Peripheral resistance reduced. The work of the left ventricle after PGE1 injection underwent two-phase changes: it increased for a short period of time and then reduced. The work of the right ventricle was activated. PGE1 caused a significant increase of the volume flow rate in the coronary (44%), femoral (83%) and superior mesenteric (59%) arteries.


Stereospecific 1,3-Aminobromination of Donor-Acceptor Cyclopropanes.
Sn(OTf)2 -catalyzed 1,3-aminobromination of donor-acceptor cyclopropanes with various sulfonyl amides or electron-poor anilines and N-bromosuccinimide is reported. These experimentally straightforward reactions occurred with complete regio- and stereospecificity (for anilines) to give γ-aminated α-brominated malonic diesters in good to excellent yields (up to 98 %). These compounds served as valuable substrates for subsequent reactions to provide substituted azetidines and γ-lactams in high yields.


Defining Population Health and Implications for Radiology.
Most definitions of population health include improved patient health, reduced inpatient stays and proce- dures, holistic care of the entire population of a country, and a general approach to improve the quality of healthcare. However, there seems to be no mention of payment for services and resources for reimbursement. The term population health can be considered a philosophy of a new model of healthcare based upon future expectations from current laws and studies from the federal government, most notably through the ACA, and healthcare organizations. Radiology departments may perform fewer procedures in the future and receive less money for these complet- ed procedures. Management will need to adjust budgets and staffing to reflect changes. Radiology departments will need to continue the current trend of doing more with less.


From capillaries to microchips, green electrophoretic features for enantiomeric separations: A decade review (2013-2022).
Enantioseparation by the electromigration-based method is well-established and widely discussed in the literature. Electrophoretic strategies have been used to baseline resolve complex enantiomeric mixtures, typically using a selector substance into the background electrolyte (BGE) from capillaries to microchips. Along with developing new materials/substances for enantioseparations, it is the concern about the green analytical chemistry (GAC) principles for method development and application. This review article brings a last decade's update on the publications involving enantioseparation by electrophoresis for capillary and microchip systems. It also brings a critical discussion on GAC principles and new green metrics in the context of developing an enantioseparation method. Chemical and green features of native and modified cyclodextrins are discussed. Still, given the employment of greener substances, ionic liquids and deep-eutectic solvents are highlighted, and some new selectors are proposed. For all the mentioned selectors, green features about their production, application, and disposal are considered. Sample preparation and BGE composition in GAC perspective, as well as greener derivatization possibilities, were also addressed. Therefore, one of the goals of this review is to aid the electrophoretic researchers to look where they have not.


Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses.
Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries. This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice. BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways. QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway. This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.


G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells.
G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer. The aim of the present study is to examine the effect of silencing GPR87 expression with a replication-deficient recombinant adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87) and to explore the underlying molecular mechanisms in bladder cancer cells. Six GPR87-expressing human bladder cancer cells, HT1197, HT1376, J82, RT112, TCCSUP and UMUC3, were used. Infection with Ad-shGPR87 effectively downregulated the GPR87 expression, and significantly reduced the percentage of viable cells in 4 of 6 cell lines as detected by an MTT assay. Significant inhibition on cell proliferation with Ad-shGPR87 was observed in the wild-type p53 bladder cancer cell lines (HT1197, RT112, TCCSUP and UMUC3), but not in the mutant p53 cells (HT1376 and J82). As represented by a wild-type p53 RT112 cell, Ad-shGPR87 infection significantly enhanced p53 and p21 expression and caused caspase-dependent apoptosis. Furthermore, the treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing RT112 xenografts. GPR87 appeared to be a promising target for gene therapy, and Ad-shGPR87 had strong antitumor effects, specifically anti-proliferative and pro-apoptotic effects, against GPR87-expressing human bladder cancer cells.


N-alkyl-4-boronopyridinium salts as thermally stable and reusable amide condensation catalysts.
[reaction: see text] N-Alkyl-4-boronopyridinium salts are highly effective and reusable catalysts for the dehydrative amide condensation reaction between equimolar mixtures of carboxylic acids and amines. N-Alkylboronopyridinium salts are thermally stabilized in the order N-alkyl-2-boronopyridinium salt << N-alkyl-3-boronopyridinium salt < N-alkyl-4-boronopyridinium salt. Homogeneous catalysts, such as 4-borono-N-methylpyridinium iodide, are more effective in the presence of ionic liquid and can be recovered by extraction with ionic liquid. In contrast, heterogeneous catalysts, such as polystyrene-bound 4-boronopyridinium salts, are effective even in the absence of ionic liquid and can be recovered by filtration.


Synthesis of Hedgehoglike F-TiO2(B)/CNT Nanocomposites for Sonophotocatalytic and Photocatalytic Degradation of Malachite Green (MG) under Visible Light: Kinetic Study.
The present study describes the preparation of hedgehoglike F-doped titanium dioxide bronze (F-TiO2(B)) and its nanocomposites containing single-walled and multiwalled carbon nanotubes (SWCNTs, MWCNTs) by using combined ball milling-hydrothermal processes. Then, sonophotocatalytic and photocatalytic degradation of malachite green (MG) dye from aqueous solution using prepared materials was performed. The results show that F-TiO2(B)/SWCNT displays a good sonophotocatalytic and photocatalytic performance among other products under visible light. In addition, they indicated that the efficiency of malachite green degradation is more than 95% and 91% for sonophotocatalytic and photocatalytic methods, respectively. Also, they demonstrate that the photocatalytic efficiency of catalysts increases in the presence of ultrasound and the sonophotocatalysis process followed a second-order kinetics. The catalysts have been characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), UV-vis diffuse reflectance spectroscopy, and energy-dispersive X-ray spectroscopy (EDX). The analyzed data confirmed the presence of CNTs and fluorine (F) as dopant in all nanocomposites. The presented hybrid method reduced the band gap from 3.02 eV for F-TiO2(B) to 2.7 eV for F-TiO2(B)/SWCNT nanocomposite.


Comparison of Application of Mitomycin C Vs Silicon Stenting Vs Conventional Method in Endonasal Dacrocystorhinostomy: A Randomized Controlled Trial of 150 Patients.
Since the days of Hippocrates, many modifications have been proposed in endonasal dacrocystorhinostomy (DCR), with the use of new drugs and implants showing variable results. The objective of this study was to analyze whether the use of silicon tubing or mitomycin C administration has an added advantage over conventional endonasal DCR. A randomized controlled trial of 150 patients between the ages of 6 and 70 years presenting with epiphora was performed. Patients were randomly divided into three groups: endonasal DCR with mitomycin C administration, endonasal DCR with silicon stenting, or conventional endonasal DCR. Patients were followed up on Days 15, 30, 60 and 90 postoperatively for sac syringing to confirm patency. The majority of patients (28.7%) were in the fourth decade of life, with a female predominance (65.3%). Dacrocystitis was most commonly seen in the left eye (58.7%). An intergroup comparison was performed using the Kruskal-Wallis test at the end of 3 and 5 months. The results suggest that the success rate was significantly higher in patients with a silicone stent (P=0.04) as compared with the other two groups, although no significant difference in failure rate was seen between patients on mitomycin C and conventional therapy (P=0.132 at Month 3 and P=0.481 at Month 5, Mann-Whitney U-test). Our study shows that silicone tube stenting had a better success rate compared with the other two groups, with no significant statistical difference between the use of mitomycin C and the conventional technique.


LSAM: L2-norm self-attention and latent space feature interaction for automatic 3D multi-modal head and neck tumor segmentation.
Objective.Head and neck (H&N) cancers are prevalent globally, and early and accurate detection is absolutely crucial for timely and effective treatment. However, the segmentation of H&N tumors is challenging due to the similar density of the tumors and surrounding tissues in CT images. While positron emission computed tomography (PET) images provide information about the metabolic activity of the tissue and can distinguish between lesion regions and normal tissue. But they are limited by their low spatial resolution. To fully leverage the complementary information from PET and CT images, we propose a novel and innovative multi-modal tumor segmentation method specifically designed for H&N tumor segmentation.Approach.The proposed novel and innovative multi-modal tumor segmentation network (LSAM) consists of two key learning modules, namely L2-Norm self-attention and latent space feature interaction, which exploit the high sensitivity of PET images and the anatomical information of CT images. These two advanced modules contribute to a powerful 3D segmentation network based on a U-shaped structure. The well-designed segmentation method can integrate complementary features from different modalities at multiple scales, thereby improving the feature interaction between modalities.Main results.We evaluated the proposed method on the public HECKTOR PET-CT dataset, and the experimental results demonstrate that the proposed method convincingly outperforms existing H&N tumor segmentation methods in terms of key evaluation metrics, including DSC (0.8457), Jaccard (0.7756), RVD (0.0938), and HD95 (11.75).Significance.The innovative Self-Attention mechanism based on L2-Norm offers scalability and is effective in reducing the impact of outliers on the performance of the model. And the novel method for multi-scale feature interaction based on Latent Space utilizes the learning process in the encoder phase to achieve the best complementary effects among different modalities.


Function of p55 and its nonerythroid homologues.
The human erythrocyte membrane has served as a model for elucidating novel protein-protein and protein-membrane interactions that have broad implications in many nonerythroid cells. A detailed analysis of erythrocyte membrane polypeptides that migrate in the region of band 4.9 led to the cloning and characterization of p55 phosphoprotein. Subsequent studies established that the p55 protein is an obligate component of the protein 4.1-glycophorin C complex, which regulates the stability and mechanical properties of the erythrocyte plasma membrane. p55 is a member of a growing family of signaling and cytoskeletal proteins termed membrane-associated guanylate kinase homologues (MAGUKs). MAGUKs are multidomain proteins consisting of either a single or three copies of the PDZ (PSD-95/Discs large/ZO-1) domain, an SH3 motif, and a guanylate kinaselike domain. Recent studies have implicated MAGUKs in the clustering of ion channels, organization of cytoskeletal elements, cell signaling events, and regulation of cell proliferation and tumor-suppression pathways. The purpose of this review is to summarize recent developments concerning the characterization of two human MAGUKs, erythrocyte p55, and lymphocyte hDIg.


A two-centre evaluation of the human organotypic skin explant culture model for screening contact allergens.
Animal models are considered to be the "gold standard" for determining the potential contact allergenicity of low molecular weight chemicals. However, governmental regulations and ethical considerations limit the use of animals for such purposes. There is therefore a need for in vitro alternative models. The human organotypic skin explant culture (HOSEC) model is reported to be a promising alternative method for the predictive testing of contact allergens. The accelerated migration of Langerhans cells from the epidermis upon exposure to contact allergens is used to identify chemicals that are potentially capable of inducing a delayed-type hypersensitivity. In the study described in this paper, the model was further refined, and used, in two independent laboratories, to screen 23 low molecular weight compounds of known classification for their allergenicity. Each laboratory was able to accurately detect the contact allergens, despite small variations in the protocols used. However, the classification of dermal irritants, which have often been falsely classified as allergens, varied between the two laboratories. Despite the current limitations of the HOSEC model, the accuracy of the predictions made (sensitiser or non-sensitiser) compare favourably with classifications obtained with commonly used animal models. The HOSEC model has the potential to be developed further as an in vitro alternative to animal models for screening for contact allergens.


Direct Electron Transfer-type Bioelectrocatalysis of Peroxidase at Mesoporous Carbon Electrodes and Its Application for Glucose Determination Based on Bienzyme System.
Non-catalytic direct electron transfer (DET) signal of Compound I of horseradish peroxidase (POD) was first detected at 0.7 V on POD/carbon nanotube mixture-modified electrodes. Excellent performance of DET-type bioelectrocatalysis was achieved with POD immobilized with glutaraldehyde on Ketjen Black (KB)-modified electrodes for H2O2 reduction with an onset potential of 0.65 V (vs. Ag | AgCl | sat. KCl) without any electrode surface modification. The POD-immobilized KB electrode was found to be suitable for detecting H2O2 with a low detection limit (0.1 μM at S/N = 3) at -0.1 V. By co-immobilizing glucose oxidase (GOD) and POD on the KB-modified electrode, a bienzyme electrode was constructed to couple the oxidase reaction of GOD with the DET-type bioelectrocatalytic reduction of H2O2 by POD. The amperometric detection of glucose was performed with a high sensitivity (0.33 ± 0.01 μA cm-2 μM-1) and a low detection limit (2 μM at S/N = 3).


Learning to Extract Building Footprints From Off-Nadir Aerial Images.
Extracting building footprints from aerial images is essential for precise urban mapping with photogrammetric computer vision technologies. Existing approaches mainly assume that the roof and footprint of a building are well overlapped, which may not hold in off-nadir aerial images as there is often a big offset between them. In this paper, we propose an offset vector learning scheme, which turns the building footprint extraction problem in off-nadir images into an instance-level joint prediction problem of the building roof and its corresponding "roof to footprint" offset vector. Thus the footprint can be estimated by translating the predicted roof mask according to the predicted offset vector. We further propose a simple but effective feature-level offset augmentation module, which can significantly refine the offset vector prediction by introducing little extra cost. Moreover, a new dataset, Buildings in Off-Nadir Aerial Images (BONAI), is created and released in this paper. It contains 268,958 building instances across 3,300 aerial images with fully annotated instance-level roof, footprint, and corresponding offset vector for each building. Experiments on the BONAI dataset demonstrate that our method achieves the state-of-the-art, outperforming other competitors by 3.37 to 7.39 points in F1-score. The codes, datasets, and trained models are available at https://github.com/jwwangchn/BONAI.git.


Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation.
The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21. The nine antigen/adjuvant formulations were assessed for stability and immunogenicity in mice in order to provide benchmarks against which other formulations could be compared, in order to assist subsequent down selection of adjuvanted vaccines. Furthermore, mouse cellular immune responses were analyzed by measuring IFN-γ and IL-5 production in splenocytes by ELISPOT, and humoral responses were determined by antigen-specific ELISA, where levels of total IgG, IgG1, IgG2b and IgG2c in serum samples were determined. The reference antigens and adjuvants described in this study, which span a spectrum of immune responses, are of potential use as tools to act as points of reference in vaccine development studies. The harmonized methodology described herein may be used as a tool for adjuvant/antigen comparison studies.


The Effect of Subepithelial Connective Tissue Graft Placement on Esthetic Outcomes After Immediate Implant Placement: Systematic Review.
Immediate implantation, despite many advantages, carries a risk of gingival recession, papilla loss, collapse of ridge contour, and other esthetic complications. Soft tissue graft placement combined with immediate implantation may be used to reduce these concerns. This review aims to systematically analyze clinical esthetic outcomes of the immediate implant combined with soft tissue graft (IMITG). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews were used. The electronic search was conducted using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 to October 2014. Quality assessments of selected articles were performed. Mid-buccal gingival level, interproximal gingival level, facial gingival thickness, gingival ridge dimension, and width of keratinized gingiva were the esthetic outcomes reviewed. Weighted mean difference of mid-buccal gingival level (WDBGL), papilla index score (WDPIS), and width of keratinized gingiva (WDKG) between initial and last measurements were calculated. Other esthetic outcomes were assessed by the descriptive analysis. Ten studies with a minimum of 6-month follow-up were included, and reported esthetic outcomes were analyzed. Mid-buccal gingival level (WDBGL, 0.07 mm; 95% confidence interval [CI] = -0.44 to 0.59; P = 0.12) and interproximal gingival level did not significantly change after IMITG (WDPIS in the mesial site, 0.31; 95% CI = -0.01 to 0.64; P = 0.06; and WDPIS in the distal site, 0.29; 95% CI = -0.06 to 0.65; P = 0.11). Width of keratinized gingiva significantly increased after IMITG (WDKG, 1.27 mm; 95% CI = -0.08 to 2.46; P = 0.04). Facial gingival thickness and gingival ridge dimension could be increased after IMITG. Because of the heterogeneity and limited number of selected studies, no conclusive statement could be made regarding the benefit of IMITG on esthetic outcomes. More randomized controlled trials are needed to provide definite clinical evidence.