Sex Disparity in Liver Transplant and Access to Living Donation.
The Model for End-stage Liver Disease (MELD)-based organ allocation system has significantly decreased mortality on the transplant waiting list for patients with end-stage liver disease. However, women have remained at a disadvantage with respect to access to deceased donor liver transplant (DDLT) even after introduction of the MELD score for organ allocation. To determine whether availability of living donation in a transplant program can offset inequity in liver transplant (LT) allocation for women. This cohort study retrospectively analyzed adult patients listed for LT at the University Health Network in Toronto, Ontario, Canada. Patients included had a potential living donor (pLD) at the moment of listing. This study was performed from November 13, 2012, to May 31, 2019. A total of 1289 listed patients (830 men; 459 women) were analyzed during the study period. This study performed survival analysis and competing-risk analysis to delineate how access to livers from living donors was associated with events in women vs men on the transplant waiting list (LT, death, or dropout). Of 1289 included patients, 459 (35.6%) were women, and the mean (SD) age was 56.1 (10.0) years at assessment and listing. A total of 783 of 1289 listed patients underwent LT. Among those with no pLD at assessment, there was a higher median (range) Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score at listing (22 [6-50] vs 19 [6-50]; P < .001) and at LT (27 [6-49] vs 20 [6-52]; P < .001) in women receiving DDLT. Women were at a significant disadvantage without a pLD (hazard ratio [HR], 1.29; 95% CI, 1.04-1.60; P = .01); there was no difference in access to LT with availability of a pLD (HR, 0.93; 95% CI, 0.76,-1.14; P = .44). The instantaneous rate of receiving a transplant in men with a pLD was 1.39 times higher than men who did not have a pLD (HR, 1.39; 95% CI; P < .001) and the instantaneous rate of receiving a transplant in women with a pLD was 1.92 times higher than in women who did not (HR, 1.92; 95% CI, 1.51-2.44; P < .001). The HR was 1.38 times higher in women compared with men across the MELD-Na score strata (HR, 1.38; 95% CI, 1.03-1.84; P = .03) and 2.04 times higher when the MELD-Na score was less than 20 (HR, 2.04; 95% CI, 1.31-3.14; P = .001). These study findings suggest that women can overcome the complex problem of allocation inequity with access to livers from living donors. Women with access only to DDLT were much more unwell than men independent of liver disease at the time of listing, dropout, or LT. Therefore, the wider availability of living donation liver transplant would be helpful in addressing the sex disparity in access to LT in the current MELD-Na era.


Holoprosencephaly-like phenotype: clinical and genetic perspectives.
We report 22 patients with normal neuropsychological development and a holoprosencephaly-like (HPE-like) phenotype screened for SHH, SIX3, TGIF, and GLI2. These patients were divided into two groups: (1) 6 patients with SHH and GLI2 mutations and (2) 16 patients with no detectable mutations. We discuss the phenotypic manifestations, evolution of the phenotype, and neuroimaging in the two groups. Conclusions about the HPE-like phenotype include (1) initial appearance as an unusually wide, and very severe unilateral cleft lip-palate in some cases; (2) variability with the expression of minor anomalies in some cases, such as single maxillary central incisor; (3) identifiable mutations in some cases and absence of mutations in others; (4) essentially normal MRI in the most cases (pituitary tumor in two cases and choroid fissure cyst in one case in Group 1; empty sella turcica in one case in Group 2); (5) intelligence within the normal range; and (6) familial aggregation in some instances. Implications include (1) thorough examination of family members for minor anomalies; (2) MRI and developmental assessment for the proband; and (3) molecular analysis.


The use of omicron-phthaldialdehyde in the detection of proteins and peptides.
A highly sensitive method utilizing omicron-phthaldialdehyde for an automated fluorescent assay of proteins and peptides is described in this paper. As an example of the utility of omicron-phthaldialdehyde, the separation of bovine serum albumin monomer from bovine serum albumin oligomers is discussed.


Nitrite plasma levels in acute and chronic coronary heart disease.
The authors carried out a study on the plasmatic levels of nitrites, which are the sole stable metabolites of nitric oxide (NO), in a group of subjects suffering from various clinical forms of coronary artery disease, aimed at evaluating the endothelial production of NO in acute and chronic ischemic conditions. Our series consisted of 104 female subjects (mean age 65 +/- 5) subdivided into: a) 10 subjects with acute coronary heart disease (myocardial infarction); b) 32 with chronic non hypertensive coronary heart disease (CHD); c) 30 with hypertensive CHD (arterial blood pressure over 160/95 mmHg); d) 32 with CHD and hypercholesterolemia (values over 250 mg/dl). Thirty-seven female subjects (mean age 58 +/- 7) without internistic diseases were considered as control subjects. For each sample the plasmatic levels of nitrites were determined by the Gutman and Hollywood method. We discovered that in the patients with chronic coronary heart disease (CHD) the mean value of nitrites was 18 +/- 0.3 mumol/L, not significantly different from the controls (17 +/- 0.5 mumol/L). In the patients with acute CHD the nitrite plasma level were significantly (p < 0.05) higher (30 +/- 2.2 mumol/L) compared to the controls and the patients with chronic CHD. In the group of patients with hypertensive CHD the mean nitrite value was 20 +/- 0.6 mumol/L, significantly (p < 0.05) higher in comparison with the group of non-hypertensive CHD patients (14 +/- 0.3 mumol/L). In the subjects with CHD and hypercholesterolemia the mean value of nitrites was sharply elevated, (25 +/- 1.0 mumol/L), with a highly significant difference (p < 0.01) as compared to the normolipemic CHD patients. These results lead to the hypothesis that: strong NO production may play a compensatory and protective role during acute myocardial hypoxia; NO defective synthesis may depend on an exhaustive endothelial adjustment in subjects with long-term CHD; a significant increase of the relaxing factor in hypertensive conditions exists; a highly enhanced synthesis of the plasmatic nitrites in hypercholesterolemic patients means an engagement of NO to neutralize the endothelium-damaging molecular substances and particularly the oxided LDL.


N/S Co-Doped 3 D Porous Carbon Nanosheet Networks Enhancing Anode Performance of Sodium-Ion Batteries.
A facile and scalable method is realized for the in situ synthesis of N/S co-doped 3 D porous carbon nanosheet networks (NSPCNNs) as anode materials for sodium-ion batteries. During the synthesis, NaCl is used as a template to prepare porous carbon nanosheet networks. In the resultant architecture, the unique 3 D porous architecture ensures a large specific surface area and fast diffusion paths of both electrons and ions. In addition, the import of N/S produces abundant defects, increased interlayer spacings, more active sites, and high electronic conductivity. The obtained products deliver a high specific capacity and excellent long-term cycling performance, specifically, a capacity of 336.2 mA h g-1 at 0.05 A g-1 , remaining as large as 214.9 mA h g-1 after 2000 charge/discharge cycles at 0.5 A g-1 . This material has great prospects for future applications of scalable, low-cost, and environmentally friendly sodium-ion batteries.


Does 2-phosphoglycolate serve as an internal signal molecule of inorganic carbon deprivation in the cyanobacterium Synechocystis sp. PCC 6803?
Cyanobacteria possess CO2 -concentrating mechanisms (CCM) that functionally compensate for the poor affinity of their ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to CO2 . It was proposed that 2-phosphoglycolate (2PG), produced by the oxygenase activity of Rubisco and metabolized via photorespiratory routes, serves as a signal molecule for the induction of CCM-related genes under limiting CO2 level (LC) conditions. However, in vivo evidence is still missing. Since 2PG does not permeate the cells, we manipulated its internal concentration. Four putative phosphoglycolate phosphatases (PGPases) encoding genes (slr0458, sll1349, slr0586 and slr1762) were identified in the cyanobacterium Synechocystis PCC 6803. Expression of slr0458 in Escherichia coli led to a significant rise in PGPase activity. A Synechocystis mutant overexpressing (OE) slr0458 was constructed. Compared with the wild type (WT), the mutant grew slower under limiting CO2 concentration and the intracellular 2PG level was considerably smaller than in the wild type, the transcript abundance of LC-induced genes including cmpA, sbtA and ndhF3 was reduced, and the OE cells acclimated slower to LC - indicated by the delayed rise in the apparent photosynthetic affinity to inorganic carbon. Data obtained here implicated 2PG in the acclimation of this cyanobacterium to LC but also indicated that other, yet to be identified components, are involved.


Total Calcanectomy and Bilateral Iliac Bone Autograft Reconstruction for the Treatment of Calcaneal Chondroblastoma Involving a Secondary Aneurysmal Bone Cyst: A Case Report and Literature Review.
Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.


An autoantibody in narcolepsy disrupts colonic migrating motor complexes.
Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.


Affective bias and current, past and future adolescent depression: a familial high risk study.
Affective bias is a common feature of depressive disorder. However, a lack of longitudinal studies means that the temporal relationship between affective bias and depression is not well understood. One group where studies of affective bias may be particularly warranted is the adolescent offspring of depressed parents, given observations of high rates of depression and a severe and impairing course of disorder in this group. A two wave panel design was used in which adolescent offspring of parents with recurrent depression completed a behavioural task assessing affective bias (The Affective Go/No Go Task) and a psychiatric interview. The affective processing of adolescents with current, prior and future depressive disorder was compared to that of adolescents free from disorder. Adolescents with current depression and those who developed depression at follow-up made more commission errors for sad than happy targets compared to adolescents free from disorder. There was no effect of prior depression on later affective processing. Small cell sizes meant we were unable to separately compare those with new onset and recurrent depressive disorder. Valence-specific errors in behavioural inhibition index future vulnerability to depression in adolescents already at increased risk and may represent a measure of affective control. Currently depressed adolescents show a similar pattern of affective bias or deficits in affective control.


New complexity for aromatic ring agostic interactions.
Density functional theory (DFT) calculations reveal that for ligand directed aromatic ring C-H bond activation, the agostic donation can share the same antibonding acceptor orbitals as a previously unrecognised π-donation from the aromatic ring of the ligand. The recognition of carbon based orbitals assisting the agostic interaction has significant implication for C-H bond activation chemistry.


SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing.
Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a "Zero-COVID" policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.


Relationship between psychological adaptability and work engagement of college teachers within smart teaching environments: the mediating role of digital information literacy self-efficacy.
Integrating the Internet and traditional teaching has enriched teaching resources and methods and introduced many advanced digital media. The smart teaching process is influenced by teachers' psychological adaptability, which can be affected by teachers' work engagement. However, the relationship between the two has not received sufficient attention in the literature. This study aims to analyze the relationship between college teachers' psychological adaptability and work engagement in a smart teaching environment. Applying structural equation modeling (SEM) to a sample of 373 front-line teachers, this study focuses on the mediating effect of digital information literacy self-efficacy on the relationship between teachers' psychological adaptability and work engagement. The results show that the four dimensions of college teachers' psychological adaptability strongly influence work engagement and digital information literacy self-efficacy. In particular, teachers' psychological adaptability and work engagement are positively correlated; teachers' self-efficacy can positively affect the three dimensions of their work engagement, and teachers' psychological adaptability can positively affect their digital information literacy self-efficacy. The above results can serve as a basis for the development and improvement of the training of college teachers and the implementation of smart teaching. The study findings highlight the importance of training teachers on information technology teaching and implementing measures to enhance teachers' digital information literacy self-efficacy. Training should focus on the knowledge and skills of teachers using information technology teaching and increase the practical links of teachers using information technology teaching.


Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation.
Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.


Structure-activity relationship (SAR) for the prediction of gas-phase ozonolysis rate coefficients: an extension towards heteroatomic unsaturated species.
Heteroatomic unsaturated volatile organic compounds (HUVOCs) are common trace components of the atmosphere, yet their diverse chemical behaviour presents difficulties for predicting their oxidation kinetics using structure-activity relationships (SARs). An existing SAR is adapted to help meet this challenge, enabling the prediction of ozonolysis rates with unprecedented accuracy. The new SAR index, x(H), correlates strongly with available literature measurements of ozonolysis rate coefficients (R(2) = 0.87), a database representing 110 species. It was found that capturing the inductive effect rather than the steric effect is of primary importance in predicting the reactivity of these species, which is to be anticipated since HUVOCs can possess a variety of functional groups with a range of electron-withdrawing and donating tendencies. New experimental measurements of ozonolysis rate coefficients were conducted for 1-penten-3-ol, 3-methyl; ethene, 1,1-dimethoxy; E-2-pentenoic acid; E-1,2-dichloroethene; Z-1,2-dichloroethene; trichloroethene; tetrachloroethene; 1-butene, 3-chloro and 2-chloropropene, and were determined to be 5.15 × 10(-18), 4.82 × 10(-16), 3.07 × 10(-18), 8.05 × 10(-20), 4.88 × 10(-21), 6.04 × 10(-22), 1.56 × 10(-24), 2.26 × 10(-18) and 1.13 × 10(-19) cm(3) molecule(-1) s(-1), respectively. The index of the inductive effect, i(H), is compared with other indices of the electron-withdrawing capacity of a substitution, notably the Taft σ* constants and the rate of reaction of a given species with the hydroxyl radical, both of which are expected to be unaffected by steric factors. i(H) correlates strongly in both cases and suggests a universal response by olefinic species towards electrophilic addition.


[Proteins specific for pregnancy in ruminants].
The bovine conceptus produces numerous signals during early pregnancy but at the present time only one protein (PSPB; pregnancy specific protein B) is detectable in the peripheral blood during the first 30 days of pregnancy. Validation criteria of the RIA for bovine PSPB have been described by Sasser et al. (1986). This review presents the results obtained in ruminants with this assay. In the bovine PSPB concentrations rise continuously during pregnancy. This protein is found in all pregnant animals at 30 days post Al. Among cows with late embryonic mortality (i.e. with high progesterone concentrations on day 21-24) only 30% present detectable PSPB concentrations between 24 and 30 days post Al. When Al are performed before 70 days post-partum, residual post- partum PSPB concentrations (from the previous pregnancy) the day of Al lowers the accuracy of positive results when PSPB RIA is used as a pregnancy test. In sheep and goat the PSPB profiles throughout pregnancy are very similar to the profile observed in the cattle. In these species the PSPB RIA may be used as a pregnancy test after 26 days post Al. In ruminants, measurement of both progesterone and PSPB in peripheral blood plasma or serum can be very useful to study the way in which various factors may chronologically affect embryonic mortality.


Perspective: Designing T-Cell Engagers With Better Therapeutic Windows.
This perspective highlights the history and challenges of developing CD3-based bispecific T-cell engagers (TCEs) as cancer therapeutics as well as considerations and potential strategies for designing the next generation TCE molecules. The goal of this article is to raise awareness of natural T-cell biology and how to best harness the tumor cell killing capacity of cytotoxic T-cells with TCEs. In light of 30 years of concerted efforts to advance TCEs in early clinical development, many of the first-generation bispecific antibodies have exhibited lackluster safety, efficacy, and manufacturability profiles. As of January 2020, blinatumomab remains the only approved TCE. Many of the current set-backs in early clinical trials implicate the high-affinity CD3 binding domains employed and the respective bispecific platforms as potential culprits. The underlying conviction of the authors is that by taking corrective measures, TCEs can transform cancer therapy. Through openness, transparency, and much needed feedback from ongoing clinical studies, the field can continuously improve the design and effectiveness of next generation T-cell redirecting therapeutics.


Enhanced fidelity of an educational intervention on skin self-examination through surveillance and standardization.
Melanoma can metastasize but is often successfully treated when discovered in an early stage. Melanoma patients and their skin check partners can learn skin self-examination (SSE) skills and these skills can be improved by practice. The purpose of this study is to determine the degree of fidelity with which educational in-person SSE intervention can be delivered by trained research coordinators to patients at risk of developing another melanoma and their skin check partners. The in-person intervention was performed in two iterations. In phase 1 (2006-2008), the research coordinators were trained to perform the intervention using a written script. In phase 2 (2011-2013), the research coordinators were trained to perform the intervention with a PowerPoint aid. Each research coordinator was individually counseled by one of the authors (KM) to insure standardization and enhance fidelity of intervention delivery. Phase 1 and Phase 2 were compared on 16 fidelity components. Further, Phase 2 fidelity was assessed by comparing mean scores of fidelity across the five research coordinators who delivered the intervention. Phase 2, which utilized a PowerPoint aid, was delivered with a higher degree of fidelity compared to phase 1with four fidelity components with significantly higher fidelity than Phase 1: 1) Explained details of melanoma, χ2 (1, n = 199)= 96.31, p < .001, 2) Discussed when to call doctor, χ2 (1, n = 199) = 53.68, p < .001 3) Explained assessment at month 1, χ2 (1, n = 199)= 12.39, p < .01, and 4) Explained assessment at month 2, χ2 (1, n = 199) = 117.75, p < .001. Further, no significant differences on mean fidelity were found across research coordinators in Phase 2. When using the PowerPoint aide, the research coordinators delivered the intervention with high fidelity (all scores >14) and there were no mean differences in fidelity across research coordinators, indicating consistency in fidelity. This can be attributed to the standardization and cueing that the PowerPoint program offered. Supervision was also a key component in establishing and maintaining fidelity of the patient educational process. This method of intervention delivery enables trained healthcare professionals to deliver an educational intervention in an effective, consistent manner.


Molecular characterization of a genomic region in a Lactococcus bacteriophage that is involved in its sensitivity to the phage defense mechanism AbiA.
A spontaneous mutant of the lactococcal phage phi31 that is insensitive to the phage defense mechanism AbiA was characterized in an effort to identify the phage factor(s) involved in sensitivity of phi31 to AbiA. A point mutation was localized in the genome of the AbiA-insensitive phage (phi31A) by heteroduplex analysis of a 9-kb region. The mutation (G to T) was within a 738-bp open reading frame (ORF245) and resulted in an arginine-to-leucine change in the predicted amino acid sequence of the protein. The mutant phi31A-ORF245 reduced the sensitivity of phi31 to AbiA when present in trans, indicating that the mutation in ORF245 is responsible for the AbiA insensitivity of phi31A. Transcription of ORF245 occurs early in the phage infection cycles of phi31 and phi31A and is unaffected by AbiA. Expansion of the phi31 sequence revealed ORF169 (immediately upstream of ORF245) and ORF71 (which ends 84 bp upstream of ORF169). Two inverted repeats lie within the 84-bp region between ORF71 and ORF169. Sequence analysis of an independently isolated AbiA-insensitive phage, phi31B, identified a mutation (G to A) in one of the inverted repeats. A 118-bp fragment from phi31, encompassing the 84-bp region between ORF71 and ORF169, eliminates AbiA activity against phi31 when present in trans, establishing a relationship between AbiA and this fragment. The study of this region of phage phi31 has identified an open reading frame (ORF245) and a 118-bp DNA fragment that interact with AbiA and are likely to be involved in the sensitivity of this phage to AbiA.


Reducing injury rates using a community-based approach.
Injuries are the number one cause of morbidity and mortality to persons aged 1-44 years in the United States. Community-based interventions offer one approach to reducing injuries. To determine whether injuries could be reduced over a 5 year period by at least 20% in a midwestern community using a proven community-based model compared with three control communities. The Injury Free Coalition for Kids of Greater Cincinnati began its injury-reducing efforts within one Intervention Community (IC) in 2000. After reviewing injury data, engaging community members, and holding focus groups to assess community needs, specific structural and social alterations were made to engage youth in safe, supervised activities and provide them with safe play places. Data were obtained from the Hamilton County Injury Surveillance System from 1999-2004 for deaths, hospitalizations, and emergency department visits. Data in our IC were compared with three control communities in the city with similar demographics and socioeconomic characteristics. 2000 Census data were used to calculate injury rates. During study period, 5065 IC youth sustained 3796 injuries, while 9297 youth from the control settings sustained 5445 injuries. Injury rate in the IC decreased 42% from 1999 to 2004, 17551.83 to 10187.56 injuries/100,000 children/year, respectively, compared with the mean rate among the three control sites, which decreased 25.7%, 12950.41 to 9626.76 injuries/100,000 children/year. This difference was statistically significant, p < 0.001. Community prevention efforts that engage youth in supervised activities and provide safe play areas can help to reduce youth injuries within specific high-risk communities.


Future technology in cochlear implants: assessing the benefit.
It has been over 50 years since Djourno and Eyries first attempted electric stimulation in a patient with deafness. Over this time, the Cochlear Implant (CI) has become not only remarkably successful, but increasingly complex. Although the basic components of the system still comprise an implanted receiver stimulator and electrode, externally worn speech processor, microphone, control system, and power source, there are now several alternative designs of these components with different attributes that can be variably combined to meet the needs of specific patient groups. Development by the manufacturers has been driven both by these various patient needs, and also by the desire to achieve technological superiority, or at least differentiation, ultimately in pursuit of market share. Assessment of benefit is the responsibility of clinicians. It is incumbent on both industry and clinicians to ensure appropriate, safe, and affordable introduction of new technology. For example, experience with the totally implanted cochlear implant (TIKI) has demonstrated that quality of hearing is the over-riding consideration for CI users. To date, improved hearing outcomes have been achieved by improvements in: speech processing strategies; microphone technology; pre-processing strategies; electrode placement; bilateral implantation; use of a hearing aid in the opposite ear (bimodal stimulation); and the combination of electric and acoustic stimulation in the same ear. The resulting expansion of CI candidacy, with more residual hearing, further improves the outcomes achieved. Largely facilitated by advances in electronic capability and computerization, it can be expected that these improvements will continue. However, marked variability of results still occurs and we cannot assure any individual patient of their outcome. Realistic goals for implementation of new technology include: improved hearing in noise and music perception; effective invisible hearing (no external apparatus); automated fitting; and reduction in outcome variability. This paper provides examples of relevant potential future technologies that can be applied to reach these goals. In the quest for better outcomes, future technology must deliver improved reliability and usability for both clinicians and recipients that does not compromise safety and is affordable. One of the challenges related to the introduction of new technologies is the 'classification' of CI systems and the framework under which sufficient change and increased benefit can be demonstrated to establish a claim of 'new generation CI' and hence increased reimbursement from third-party payers. Significant improvements in hearing outcomes and quality of life associated with CI design changes are difficult to measure, particularly when there is such dramatic benefit from the intervention of cochlear implantation from the individual's perspective. Manufacturers and clinicians need to be objective and undertake appropriate safety studies and long-term and multi-centre clinical trials to ensure that the introduction of new technology is both safe and effective and supported by health systems worldwide.


Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries.
Cat carotid arteries that have an intact endothelium were isolated and perfused with Krebs-Henseleit solution containing recombinant human tumor necrosis factor (rhTNF). Perfused arteries were preconstricted with KCl and then dilated with acetylcholine (ACh) or acidified NaNO2. After perfusion with TNF (4 micrograms/ml) for 120 min, the ACh-induced vasodilator response was markedly blunted, but the NaNO2 vasodilator response was not significantly affected. Arteries perfused with 2 micrograms/ml TNF for 60-120 min or with 4 micrograms/ml for 60 min did not develop a significantly impaired relaxation to ACh. Moreover, perfusion with 20-100 micrograms/ml cycloheximide, an inhibitor of protein synthesis, blocked the TNF-induced impairment of the relaxation to ACh. On the other hand, the vasodilator response to acidified NaNO2 did not change in any perfused carotid arteries. These results suggest that TNF promotes the synthesis of proteins that contribute to the damage of endothelial cells directly, probably by inhibiting endothelium-derived relaxing factor release.


Clinicopathological features and prognosis in elderly gastric cancer patients: a retrospective cohort study.
Little is known about the clinicopathological features and prognosis in elderly gastric cancer (GC) patients aged 65-79 years. The aim of this study was to evaluate clinicopathological features and prognosis in elderly GC patients. From May 2008 to December 2014, a total of 5,282 GC patients were enrolled in our present study. Patients were divided into elderly and middle-aged groups. The clinicopathological features and clinical outcomes were analyzed. The proportion of dysphagia was significantly higher in elderly patients than that in middle-aged patients (P=0.002), whereas the proportion of abdominal pain and heartburn was significantly lower in elderly patients than that in middle-aged patients (P<0.001 vs P=0.038, respectively). The proportion of patients with carbohydrate antigen (CA) 19-9 was significantly higher in elderly patients than that in middle-aged patients (P=0.009). There was no significant difference in clinicopathological features between elderly and middle-aged patients with D2 gastrectomy (all P>0.05). Age, tumor size, histological type, tumor depth, lymph node metastasis, carcinoembryonic antigen, alpha fetoprotein, CA19-9, and CA125 were independent risk factors for the prognosis of GC patients in univariate and multivariate analyses. Overall survival in elderly patients was significantly reduced compared with middle-aged patients (P=0.001), especially in patients with tumor size >5 cm (P=0.002), poorly differentiated tumor (P<0.000), stage III tumor (P=0.002), or normal levels of carcinoembryonic antigen (P=0.009), alpha fetoprotein (P=0.002), CA19-9 (P=0.002), and CA125 (P=0.004). The clinicopathological features of elderly patients were different to those of middle-aged patients. The prognosis for elderly GC patients was significantly worse than for middle-aged patients.


Drought and resprouting plants.
Many species have the ability to resprout vegetatively after a substantial loss of biomass induced by environmental stress, including drought. Many of the regions characterised by ecosystems where resprouting is common are projected to experience more frequent and intense drought during the 21st Century. However, in assessments of ecosystem response to drought disturbance there has been scant consideration of the resilience and post-drought recovery of resprouting species. Systematic differences in hydraulic and allocation traits suggest that resprouting species are more resilient to drought-stress than nonresprouting species. Evidence suggests that ecosystems dominated by resprouters recover from disturbance more quickly than ecosystems dominated by nonresprouters. The ability of resprouters to avoid mortality and withstand drought, coupled with their ability to recover rapidly, suggests that the impact of increased drought stress in ecosystems dominated by these species may be small. The strategy of resprouting needs to be modelled explicitly to improve estimates of future climate-change impacts on the carbon cycle, but this will require several important knowledge gaps to be filled before resprouting can be properly implemented.


Benign childhood epilepsy with centro-temporal spikes: correlation between clinical, cognitive and EEG aspects.
Benign childhood epilepsy with centro-temporal spikes (BECTS) is a form of epilepsy with no demonstrable anatomical lesion showing spontaneous seizure remission. During the active phase of the disease the children may show cognitive deficits. The objective of this study was to assess, in children with BECTS, the relationship between clinical-EEG aspects and performance in the school performance test (SPT), Raven's progressive matrixes test and the Wechsler Intelligence Scale for Children (WISC-III). Forty-two 7 to 11 year old children were included and the following tests carried out: anamnesis, neurological examination, electroencephalogram (EEG), SPT, Raven's test and WISC-III. The children with BECTS had normal IQ values but showed inferior performance in the SPT more frequently than "healthy" children, paired with respect to age and maternal scholastic level. There was moderate positive correlation between WISC-III results and the age when the seizures started and the educational level of the parents. On the other hand, aspects linked to the epileptic nature of BECTS, such as the number of seizures, time since last seizure and the number and lateralization of the centro-temporal spikes on the EEG, showed no correlation with the neuropsychological tests.


Start-Up and Aeration Strategies for a Completely Autotrophic Nitrogen Removal Process in an SBR.
The start-up and performance of the completely autotrophic nitrogen removal via nitrite (CANON) process were examined in a sequencing batch reactor (SBR) with intermittent aeration. Initially, partial nitrification was established, and then the DO concentration was lowered further, surplus water in the SBR with high nitrite was replaced with tap water, and continuous aeration mode was turned into intermittent aeration mode, while the removal of total nitrogen was still weak. However, the total nitrogen (TN) removal efficiency and nitrogen removal loading reached 83.07% and 0.422 kgN/(m3·d), respectively, 14 days after inoculating 0.15 g of CANON biofilm biomass into the SBR. The aggregates formed in SBR were the mixture of activated sludge and granular sludge; the volume ratio of floc and granular sludge was 7 : 3. DNA analysis showed that Planctomycetes-like anammox bacteria and Nitrosomonas-like aerobic ammonium oxidization bacteria were dominant bacteria in the reactor. The influence of aeration strategies on CANON process was investigated using batch tests. The result showed that the strategy of alternating aeration (1 h) and nonaeration (1 h) was optimum, which can obtain almost the same TN removal efficiency as continuous aeration while reducing the energy consumption, inhibiting the activity of NOB, and enhancing the activity of AAOB.


A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor.
The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and biological activity of the indenoisoquinoline analogues. Collectively, the analysis of methoxy groups on the indenone ring also illustrates a strict steric requirement for substituents extending toward the nonscissile DNA backbone and emphasizes a need for planarity to afford potent biological activity.


Cutaneous laser-Doppler flowmetry: influence of underlying muscle blood flow.
To find whether the measurement of skin blood flow (SkBF) by laser-Doppler flowmetry (LDF) is influenced by blood flow to underlying skeletal muscle, five subjects performed mild forearm exercise to induce a metabolic hyperemia in muscle in both forearms. This exercise consisted of alternative opening and closing of both hands at a frequency of approximately 1/s for a duration of 3 min. This exercise was performed twice by each subject. Forearm blood flow (FBF) by plethysmography increased from 2.64 +/- 0.49 (rest) to 31.11 +/- 9.95 ml.100 ml-1.min-1 (immediately after exercise) (P less than 0.001). No statistically significant postexercise increase was observed in LDF measured on the dorsal (110 +/- 21 to 105 +/- 21 mV) or ventral surface (266 +/- 113 to 246 +/- 77 mV) of the forearm. LDF measured from the chest also showed no significant change, indicating that the exercise was too mild to have reflex effects on SkBF. Moreover, the slope of the logarithmic linear regression and the half-time for recovery during the postexercise period for FBF were not reflected in LDF measurements from any of the three sites. We conclude that LDF measured from the skin surface is not influenced by blood flow to underlying skeletal muscle.


Morphological study of styloid process of the temporal bone and its clinical implications.
The objective of this study was to study the morphometry of the styloid process of temporal bone and prevalence of elongated styloid process. The morphology of elongated styloid process along with its embryological and clinical importance are discussed. The present study included 110 human dry skulls which were procured from the bone collections of the department of anatomy. The styloid process was observed macroscopically on both sides of all the skulls, the elongations if any were noted. All the styloids were measured for their length, thickness at different levels and interstyloid distance at various levels. Out of 110 specimens, only 5 skulls (4.5%) exhibited the elongated styloid process. Among them, 3 skulls (2.7%) had unilateral elongation and 2 skulls (1.8%) had bilateral elongation of the styloid process. The mean length of the styloid process was 17.8±9.3 mm and 18.2±5.6 mm for the right and left sides, respectively. The prevalence of elongated styloid process in the present study was 4.5%. The clinical anatomy of this congenital variant is important to the neurosurgeon and radiologist, while interpreting the computed tomogram and magnetic resonance image scans. The morphological knowledge of elongated styloid process is clinically important since the course of the vertebral artery may be distorted in such situations.


Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.
Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.


The unbiased estimation of number and sizes of arbitrary particles using the disector.
A three-dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented. Used in combination with ordinary and recently developed stereological methods unbiased estimates of various mean particle sizes and the variance of particle volume are obtainable on sets of two parallel sections with a known separation. The same principle allows the unbiased estimation of the distribution of individual particle volumes in sets of serial sections.


RNA sequencing reveals upregulation of a transcriptomic program associated with stemness in metastatic prostate cancer cells selected for taxane resistance.
Patients with metastatic castration-resistant prostate cancer (mCRPC) develop resistance to conventional therapies including docetaxel (DTX). Identifying molecular pathways underlying DTX resistance is critical for developing novel combinatorial therapies to prevent or reverse this resistance. To identify transcriptomic signatures associated with acquisition of chemoresistance we profiled gene expression in DTX-sensitive and -resistant mCRPC cells using RNA sequencing (RNA-seq). PC3 and DU145 cells were selected for DTX resistance and this phenotype was validated by immunoblotting using DTX resistance markers (e.g. clusterin, ABCB1/P-gp, and LEDGF/p75). Overlapping genes differentially regulated in the DTX-sensitive and -resistant cells were ranked by Gene Set Enrichment Analysis (GSEA) and validated to correlate transcript with protein expression. GSEA revealed that genes associated with cancer stem cells (CSC) (e.g., NES, TSPAN8, DPPP, DNAJC12, and MYC) were highly ranked and comprised 70% of the top 25 genes differentially upregulated in the DTX-resistant cells. Established markers of epithelial-to-mesenchymal transition (EMT) and CSCs were used to evaluate the stemness of adherent DTX-resistant cells (2D cultures) and tumorspheres (3D cultures). Increased formation and frequency of cells expressing CSC markers were detected in DTX-resistant cells. DU145-DR cells showed a 2-fold increase in tumorsphere formation and increased DTX resistance compared to DU145-DR 2D cultures. These results demonstrate the induction of a transcriptomic program associated with stemness in mCRPC cells selected for DTX resistance, and strengthen the emerging body of evidence implicating CSCs in this process. In addition, they provide additional candidate genes and molecular pathways for potential therapeutic targeting to overcome DTX resistance.


Estrogen receptor analysis on needle aspirates from human mammary carcinoma.
Immediately after mastectomy, estrogen receptor concentration was measured in fine needle aspirates and in histologic tissue specimens from 13 human breast carcinomas. Fine needle aspirates were shown to contain enough material for receptor analysis when the sensitive method of isoelectric focusing in slabs of polyacrylamide gel was used for receptor determination. Aspirations with two different needles (outer diameter 0.7 and 1.4 mm) from each tumor yielded highly correlated receptor values (r = 0.97, p less than 0.0001). There was also a highly significant correlation (r = 0.91, p less than 0.0001) between the receptor content in needle aspirates and in tissue specimens from the same tumor.


Presence of immunoreactive vasoactive intestinal polypeptide in anterior pituitary of normal male and long term estrogen-treated female rats: a light microscopic immunohistochemical study.
The presence and synthesis of vasoactive intestinal polypeptide (VIP) has been demonstrated in the rat anterior pituitary. It was recently confirmed that immunoreactive VIP is present in the anterior pituitary, and in a thyroid-deficient state, VIP could be detected by light microscopic immunohistochemistry. It has also been suggested that VIP plays a stimulatory role in PRL secretion. To gain more detailed information on the localization of VIP and the conditions that alter the synthesis of VIP, we examined VIP immunoreactivity using immunohistochemistry in pituitaries of normal male and cycling female rats and in those states in which PRL secretion was enhanced (pregnancy, lactation, long term estrogen treatment, and pituitary implanted under kidney capsule of normal or estrogen-treated female rats). In situ, implanted and cultured pituitary cells were stained for VIP immunoreactivity using the peroxidase-antiperoxidase method. VIP immunoreactivity was observed in about 45% of the male rats, in all estrogen-treated female rats, in the implanted pituitaries under the kidney capsule (three of five from estrogen-treated and one of five from intact females, respectively), and in the pituitary cell cultures derived from estrogen-treated rats. Using a double labeling procedure we have also observed PRL immunoreactivity in a small population of the VIP-positive cells. These results suggest a positive regulatory role of estrogen in expression of the VIP gene. The physiological and pathophysiological significance of VIP in PRL secretion, however, remains to be clarified.


Molecular determinants of recognition for the intestinal peptide carrier.
Computer-aided conformational analysis was used to characterize the pharmacophore for the intestinal peptide carrier. The active analog approach to pharmacophore building was applied as implemented in the SYBYL software package. Conformational analysis and MOPAC calculations were used to determine the lowest energy conformation of carrier substrates, as well as the conformations of compounds that displayed a common pharmacophoric geometry (i.e., inhibitors and inactive structural analogs). A pharmacophore map was calculated, and based on structural mutualities and functional topology, three substrate groups were suggested: compounds that bind to the transporter and are transferred across the membrane; compounds that show affinity for the peptide carrier (i.e., known to inhibit transport of substrates) but are not transferred across the membrane; and compounds that contain the pharmacophoric geometry but show no affinity for the carrier. Affinity for the peptide transporter can be diminished or abolished in either of three ways: esterification of the free carboxylic acid moiety; introduction of a second negative group; and intramolecular steric hindrance of the free carboxylic acid by either side chains with a positively charged nitrogen function or groups capable of hydrogen bond formation.


Factors associated with cutaneous colonization of Mucormycetes in diabetic and non-diabetic individuals.
This study was conducted to assess factors associated with cutaneous colonization of Mucormycetes in diabetic and non-diabetic individuals. A total of 800 swab samples from 200 participants including 100 diabetics and 100 non-diabetics were collected from four different body sites: (1) the forehead, (2) nasal cavity, (3) hands and (4) feet. Fungal isolation, fungal identification and antibiotic sensitivity tests were performed on the isolates. Overall, 12.0 % of the participants showed Mucormycetes colonization while the commonest fungal isolates were Mucor Species (Spp.). followed by Rhizopus spp. Diabetics had a 11 times higher odds of colonization compared to non-diabetics. The majority of the isolates were resistant to itraconazole; however, all isolates were sensitive to amphotericin B. A significant association was observed between profession and Mucormycetes (P=0.03) with significantly higher colonization in retired people compared to business people. Higher odds of colonization were demonstrated among older ages, lower class status and individuals with prolonged contact time with soil.


Hierarchical Nanoassemblies-Assisted Combinational Delivery of Cytotoxic Protein and Antibiotic for Cancer Treatment.
Protein therapeutics hold increasing interest with the promise of revolutionizing the cancer treatment by virtue of a potent specific activity and reduced adverse effects. Nonetheless, the therapeutic efficacy of anticancer proteins is highly compromised by multiple successive physiological barriers to protein delivery. In addition, concurrent elimination of bulk tumor cells and highly tumorigenic cancer stem-like cells (CSCs) as a promising strategy has been evidenced to significantly improve cancer therapy. Here we show that a hierarchically assembled nanocomposite can self-adaptively transform its particulate property in response to endogenous tumor-associated signals to overcome the sequential barriers and achieve an enhanced antitumor efficacy by killing CSCs and bulk tumor cells synchronously. The nanoassemblies preferentially accumulate in tumors and dissociate under tumor microenvironmental acidity accompanied by the extracellular release of small-sized ribonuclease A (RNase A)-encapsulated nanocapsule (R-rNC) and small-molecule anti-CSC doxycycline (Doc), which exhibit increased tumor penetration and intracellular accumulation. The endocytosed R-rNC rapidly releases RNase A within both CSCs and tumor cells at intracellular reductive conditions, causing cell death by catalyzing RNA degradation, while Doc eradicates CSCs by inhibiting the mitochondrial biogenesis. The hierarchical assemblies show enhanced cytotoxicity on the CSC-enriched MDA-MB-231 mammospheres and an enhanced antitumor efficacy on the xenograft tumor mouse model.


Early Detection of Iron Overload Cardiomyopathy in Transfusion Dependent Thalassemia Patients in Sulaimaniyah City, Iraq.
Lifelong blood transfusion is recommended for patients with transfusion-dependent thalassemia (TDT) that lead to iron overload and results in cardiomyopathy (CM). To assess the accuracy of several electrocardiographic (ECG) data in patients at high risk of arrhythmia, early detection of structural and functional changes in left atrium and ventricle using ECG and echocardiography (two dimensional, M-mode echocardiography along with Doppler studies), and to observe the correlations between plasma B-type atrial natriuretic peptide (BNP)/serum ferritin and ECG with Doppler as well as echocardiographic changes in patients with TDT. The current prospective case-control study included 75 TDT patients and 74 control subjects with the mean age of 9.55 and 9.93 years, respectively. Participants were assessed for the socio-demographic, physical examinations, serum ferritin, plasma BNP, ECG, 2D echocardiography, and tissue/pulse wave Doppler. The mean of serum ferritin and plasma BNP were significantly (p<0.001) higher in the cases (1475.19 ng/mL and 47.63 pg/mL, respectively) than controls (41.3 ng/mL and BNP 23.37 pg/mL, respectively). ECG findings showed significant higher P-wave dispersion, QRS duration, QT duration and dispersion, and JTc dispersion in cases than controls. Echocardiography findings revealed diastolic dysfunction with preserved ejection fraction (EF) in thalassemia cases, as well as significant higher left ventricular (LV) mass, LV internal diameters during systole and diastole (LVIDs and d) and LV posterior wall thickness during diastole (LVPWd) in cases than controls (p<0.05). Also, a significant (p<0.05) correlation between BNP and QT dispersion was found in patients. These findings suggest the usefulness of ECG, 2D echocardiographic, Doppler studies and plasma BNP, with no significant beneficial effect of serum ferritin level in detecting early cardiac changes in patients with TDT.


Daidzein enhances intramuscular fat deposition and improves meat quality in finishing steers.
An experiment was conducted to determine the effects of soy isoflavone daidzein on carcass characteristics, fat deposition, meat quality, and blood metabolites in finishing steers. Fourteen crossbred steers were used in a 120-d finishing study. These steers were stratified by weight into groups and randomly allotted by group to one of two dietary treatments: (1) control and (2) daidzein (500 mg/kg concentrate). The steers were fed a 90% concentrate diet. Supplemental daidzein did not affect slaughter weight, hot carcass weight, and dressing percentage, but tended to reduce fat proportion (not including intramuscular fat) in carcass and backfat thickness of steers. The carcass bone proportion was greater in steers fed daidzein diets than those fed control diets. Daidzein supplementation reduced pH at 24 h after slaughtered and moisture content and increased isocitrate dehydrogenase activity, fat content (16.28% and 7.94%), marbling score (5.29 and 3.36), redness (a*), and chroma (C*) values in longissimus muscle relative to control treatment. The concentrations of blood metabolites including glucose, blood urea nitrogen, triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were all lower in steers fed daidzein diets than those fed control diets. Current results suggest that supplemental daidzein can affect lipid metabolism, increase intramuscular fat content and marbling score, and improve meat quality in finishing steers. Daidzein should be a promising feed additive for production of high-quality beef meat.


Super-stoichiometric charge neutralization in particle-polyelectrolyte systems.
The adsorption of poly(vinylamine) (PVA) on poly(styrene sulfate) latex particles is studied, and its consequences on the charging behavior and suspension stability are investigated. The adsorption process is assessed by batch depletion experiments and time-resolved electrophoretic mobility measurements. The adsorption of PVA appears to be basically irreversible. The rate of adsorption decreases with decreasing polymer dose. At low polymer dose, the polymer coverage corresponds to the amount of the polyelectrolyte added, while at high polymer dose, the polymer coverage saturates the surface. Stability ratios are determined by dynamic light scattering, and strongly depend on the polymer dose and salt level. The aggregation is rapid near the isoelectric point (IEP), and it slows down when moving away from it. The charge neutralization is highly nonstoichiometric with charging ratios (CR) larger than unity, meaning that several charges on an adsorbed polyelectrolyte chain are necessary to neutralize a single charge on the particle surface. By comparing the IEP for particles and polyelectrolytes of different charge densities, we find a strong dependence of the CR on the mismatch between the average distances between individual charges on the surface and on the polyelectrolyte. A simple model is proposed to explain this trend.


Extended-hours palliative care service with a hospital-avoidance and enhanced-care approach: report of a quality improvement project.
A community palliative care service (CPCS) identified its after-hours support as sub-optimal in avoiding acute hospitalisation and supporting patients to remain at home. It created and conducted a pilot of an extended hours palliative care service (EHPCS) using current resources. To evaluate the efficacy of an extended hours palliative care service pilot. Retrospective chart review of after-hours calls taken before the trial, usual care, was undertaken. During the trial, quantitative data was gathered of the outcome of each after-hours call, including outcomes of occasion of service, reason for and length and times of calls. The extended hours palliative care service, compared with usual care, showed an almost 50% decrease in acute hospitalisation, nearly doubled after-hours palliative care unit admission and a 17% increase in patients staying in their home. EHPCS was positively received by CPCS staff, despite cost and workforce impact. EHPCS can positively impact on reducing avoidable hospitalisations and facilitate palliative care patients to be in their preferred place of care.


Normal pressure subdural hygroma with mass effect as a complication of decompressive craniectomy.
Subdural posttraumatic collections are called usually Traumatic Subdural Hygroma (TSH). TSH is an accumulation of cerebrospinal fluid (CSF) in the subdural space after head injury. These collections have also been called Traumatic Subdural Effusion (TSE) or External Hydrocephalous (EHP) according to liquid composition, or image features. There is no agreement about the pathogenesis of these entities, how to define them or if they are even different phenomena at all. We present a case of a complex posttraumatic subdural collection, the role of cranioplasty as definite solution and review the literature related to this complication. Patients who undergo decompressive craniectomy (DC) have a risk of suffering a subdural collection of 21-50%. Few of these collections will become symptomatic and will need evacuation. When this happens, cranioplasty might be the definitive solution.


Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury.
Cardiac surgery with cardiopulmonary bypass (CPB) results in perioperative organ damage caused by the systemic inflammatory response syndrome (SIRS) and ischemia/reperfusion injury. Administration of corticosteroids before CPB has been demonstrated to inhibit the activation of the systemic inflammatory response. However, the clinical benefits of corticosteroid therapy are controversial. This study was designed to document the effects of dexamethasone on cytokine release and perioperative myocardial, pulmonary, renal, intestinal, and hepatic damage, as assessed by specific and sensitive biomarkers. A prospective, double-blind, placebo-controlled, randomized trial for dexamethasone was conducted in 20 patients receiving either dexamethasone (1 mg/kg before anesthesia induction and 0.5 mg/kg after 8 h; n = 10) or placebo (n = 10). Different markers were used to assess the SIRS: interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and tryptase; and organ damage: heart (plasma heart-type fatty acid binding protein, cardiac troponin I [cTnI], creatine kinase-MB), kidneys (N-acetyl-glucosaminidase [NAG], microalbuminuria), intestine (intestinal-type fatty acid binding protein [I-FABP]/liver-type fatty acid binding protein [L-FABP]), and liver (alpha-glutathione S-transferase). Dexamethasone modulated the SIRS with lower proinflammatory (IL-6, IL-8) and higher antiinflammatory (IL-10) IL levels. CRP and tryptase were lower in the dexamethasone group. cTnI values were lower in the dexamethasone group at 6 h in the ICU (p = 0.009). Patients in the dexamethasone group had a longer time to tracheal extubation (18.86 +/- 1.13 h vs 15.01 +/- 0.99 h, p = 0.02 [mean +/- SEM]), with a lower oxygenation index at that time: Pa(O2)/fraction of inspired oxygen ratio, 37.17 +/- 1.8 kPa vs 29.95 +/- 2.1 kPa (p = 0.009). The postoperative glucose level (10.7 +/- 0.6 mmol/L vs 7.4 +/- 0.5 mmol/L, p = 0.005) was higher in the dexamethasone group. Serum glucose was independently associated with intestinal injury (urine I-FABP peak, R2 = 42.5%, beta = 114.4 +/- 31.4, significant at p = 0.002; urine L-FABP peak, R2 = 47.3%, beta = 7,714.1 +/- 1,920.9, significant at p = 0.001) and renal injury (urine NAG, R2 = 32.1%, beta = 0.21 +/- 0.07, significant at p = 0.009). Tryptase peaks correlated negatively with peaks of intestinal and renal injury biomarkers. Even while inhibiting SIRS, dexamethasone treatment offered no protection against transient, subclinical, perioperative abdominal organ damage. Tryptase release could have a preconditioning effect, offering protection against perioperative intestinal and renal damage. Dexamethasone treatment resulted in more pronounced postoperative pulmonary dysfunction, prolonged time to tracheal extubation, and initiated postoperative hyperglycemia in patients undergoing elective on-pump coronary artery bypass graft surgery.


SQYZ granules, a traditional Chinese herbal, attenuate cognitive deficits in AD transgenic mice by modulating on multiple pathogenesis processes.
The pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide aggregation, inflammation, oxidative stress, and others. Effective therapeutic drugs for treating AD are urgently needed. SQYZ granules (SQYZ), a Chinese herbal preparation, are mainly composed of the ginsenoside Rg1, astragaloside A and baicalin, and have been widely used to treat dementias for decades in China. In this study, we found the therapeutic effects of SQYZ on the cognitive impairments in an AD mouse model, the β-amyloid precursor protein (APP) and presenilin-1 (PS1) double-transgenic mouse, which co-expresses five familial AD mutations (5XFAD); next, we further explored the underlying mechanism and observed that after SQYZ treatment, the Aβ burden and inflammatory reactions in the brain were significantly attenuated. Through a proteomic approach, we found that SQYZ regulated the expression of 27 proteins, mainly those related to neuroinflammation, stress responses and energy metabolism. These results suggested that SQYZ has the ability to improve the cognitive impairment and ameliorate the neural pathological changes in AD, and the therapeutic mechanism may be related to the modulation of multiple processes related to AD pathogenesis, especially anti-neuroinflammation, promotion of stress recovery and improvement of energy metabolism.


SARGE: a tool for creation of putative genetic networks.
SARGE is a tool for creating, visualizing and manipulating a putative genetic network from time series microarray data. The tool assigns potential edges through time-lagged correlation, incorporates a clustering mechanism, an interactive visual graph representation and employs simulated annealing for network optimization. The application is available as a .jar file from http://www.bioinformatics.cs.ncl.ac.uk/sarge/index.html.


Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.
Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders.


Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.
We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke (P=0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack.


Satisfaction with quality of life varies with temperament types of patients with schizophrenia.
We sought to explore the relationships of three temperament factors with domain-specific subjective quality of life (QOL) of patients with schizophrenia. Ninety patients with schizophrenia were evaluated using the Quality of Life Enjoyment and Life Satisfaction Questionnaire, the Tridimensional Personality Questionnaire, the Positive and Negative Syndromes Scale, the Distress Scale for Adverse Symptoms, the Insight and Treatment Attitudes Questionnaire, the Insight Self-Report Scale, and standardized questionnaires for self-reported emotional distress and stress process-related variables. Predictors of domain-specific QOL were identified using multiple regression techniques. Temperament factors explain 6% to 16% of variability in QOL domain scores among patients with schizophrenia after controlling for the remaining variables (emotional distress, social support, self-esteem, avoidance coping, age, side effects, and depression). We found that higher levels of novelty seeking are associated with better general QOL, physical health, and more positive subjective feelings, whereas higher levels of reward dependence are related to better satisfaction from social relationships. Higher levels of harm avoidance are associated with poorer satisfaction with general activities, and medication. Thus, temperament factors, as assessed by the Tridimensional Personality Questionnaire, substantially influence satisfaction with life quality in schizophrenia. Novelty seeking, reward dependence, and harm avoidance are associated with different domains of QOL.


Natural T cell immunity against cancer.
It has long been a matter of debate whether tumors are spontaneously immunogenic in patients. With the availability of sensitive methods, naturally occurring T cells directed against tumor-associated antigens (TAAs) can be frequently detected in cancer patients. In this review, we summarize the current data on T cell responses to TAAs in various malignancies, including melanoma, colorectal cancer, leukemia, and breast cancer. T cell responses against various antigens, including melanoma differentiation antigens, carcinoembryonic antigen, epithelial cell adhesion molecule, her-2/neu, Wilms' tumor protein, proteinase 3, NY-ESO-1, and surviving, have been reported in a substantial number of patients. In contrast, other TAAs, including most antigens of the MAGE family, do not usually elicit spontaneous T cell responses. A distinction between direct ex vivo T cell responses and in vitro-generated T cell responses is provided because in vitro stimulation results in quantitative and functional changes of T cell responses. The possible role of TAA-specific T cells in immunosurveillance and tumor escape and the implications for immunological treatment strategies are discussed. Naturally occurring T cells against TAAs are a common phenomenon in tumor patients. Understanding the mechanisms and behavior of natural TAA-specific T cells could provide crucial information for rational development of more efficient T cell-directed immunotherapy.


The Affordable Care Act and Cancer Care for Young Adults.
The Affordable Care Act (ACA) requires health plans that provide coverage for dependents to cover adult children to age 26 years. Extensive evidence has shown that since its implementation in September 2010 insurance coverage and access to care for young adults in the general population have increased. This article reviews the studies that have evaluated the impacts of the ACA on access to cancer care and outcomes for young adults aged 19 to 25 years. Current literature shows that the ACA increased insurance rate and cancer diagnosis at early stage for young adults. There is also evidence of the ACA's positive effects on initiation and completion of human papillomavirus vaccination and receipt of fertility-sparing treatment for cervical cancer among young women. Several avenues of future research on the ACA and cancer care are suggested.


Uridine triphosphate increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor.
The aim of this study was to investigate the effect of uridine triphosphate (UTP) on the proliferation of human cancerous pancreatic duct epithelial cells. Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into the pancreatic cell line PANC-1. Effect of UTP was assayed using selective P2 agonist and antagonist, small interfering RNA, intracellular signal inhibitors, and Western blot. Incubation of PANC-1 cells with UTP or MRS2768, a selective P2Y2 receptor agonist, resulted in a dose- and time-dependent increase of proliferation. The messenger RNA transcript and protein of P2Y2 receptor were expressed in PANC-1 cells. P2 receptor antagonist suramin and small interfering RNA against P2Y2 receptor significantly decreased the proliferative effect of UTP and MRS2768. Activation of P2Y2 receptor by UTP transduced to phospholipase C, inositol 1,4,5-triphosphate (IP3), and protein kinase C. Uridine triphosphate-induced proliferation was mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increased phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K. Uridine triphosphate increases proliferation of human pancreatic duct epithelial cells by activation of P2Y2 receptor and PI3K/Akt pathway. This could be helpful for discovering the long-term roles of P2Y2 receptor in pancreatic cells.


Pattern of treatment among diabetic patients in France.
Both the treatment pattern and the degree of metabolic control were estimated from a sample of 1172 French diabetic patients. The subjects were recruited from 80 medical-analysis laboratories scattered throughout the country, where they came for biologic blood sample tests. Patients had to be diagnosed as having diabetes, give consent for additional blood sampling, and fill out a short self-questionnaire. Glycosylated hemoglobin A1c (HbA1c) was centrally determined by liquid chromatography (normal range 3.5-6.3%). We found 135 patients (11.5%) who were not drug treated or treated with diet alone, 862 (73.5%) treated with oral agents, and 175 (15.0%) treated with insulin. Among the latter, 79 (6.7%) were defined as true insulin-dependent diabetes mellitus (IDDM) patients. Among patients receiving no drug or a slight dosage or oral agents, 47% were found to be in the normal range of HbA1c. On the other hand, among the patients intensively treated with oral agents or secondarily with insulin, less than half were under fair control (HbA1c less than 7.5%). These results are in agreement with previous estimates of treatment distribution derived from national drug sales data. They provide evidence regarding the particular features of diabetes in France, i.e., low prevalence of IDDM, low consumption of insulin, high consumption of oral agents. The finding of a large proportion of normal HbA1c values in non-insulin-dependent diabetic patients suggests a state of overdiagnosis linked to the use of nonspecific criteria of diagnosis in large-scale screening.


Clearance from the anterior chamber of RBCs from human diabetics.
Erythrocytes from diabetic patients manifest decreased deformability and increased adherence. These abnormal membrane properties may diminish the ability of erythrocytes (RBCs) from diabetics to undergo deformation in passage through the trabecular meshwork. Using sodium chromate Cr 51-labeled RBCs from type I diabetic patients with proliferative retinopathy and normal control subjects, we studied RBC clearance from the rabbit anterior chamber. The mean time for 50% clearance (T50) of RBCs from diabetics (76 hours) was significantly longer than that for RBCs from normal subjects (19.5 hours). In this model, RBCs from diabetics have a slower clearance from the anterior chamber than do RBCs from normal subjects.


Sarcomatoid carcinoma of the urinary bladder. A clinicopathologic analysis of 12 cases and review of the literature.
Twelve carcinomas of the urinary bladder with a prominent component of spindle-shaped cells (sarcomatoid carcinomas) that arose in patients from 60 to 83 (average, 71.5 years) years of age are reported. The seven male and five female patients typically complained of hematuria. Seven tumors were sessile and five were polypoid. On microscopic examination, the malignant spindle cells merged with in situ transitional cell carcinoma or various forms of invasive carcinoma, including transitional cell carcinoma (11 cases), adenocarcinoma (2 cases), squamous cell carcinoma (2 cases), and small cell undifferentiated carcinoma (2 cases). Immunocytochemical stains were performed in 11 cases; the spindle cells stained for cytokeratin, epithelial membrane antigen, and vimentin. Limited follow-up in this series does not allow for conclusions concerning differences in behavior between sarcomatoid carcinoma and conventional transitional cell carcinoma of similar grade and stage. However, the typically deep invasion of the former tumors and their histologic features indicate that they are highly aggressive neoplasms.


THE EFFECT OF HOST PLANT PATCH SIZE VARIATION ON THE POPULATION STRUCTURE OF A SPECIALIST HERBIVORE INSECT, TETRAOPES TETRAOPHTHALMUS.
The patchy local distribution of the common milkweed, Asclepias syriaca, organizes populations of a beetle that feeds on it, Tetraopes tetraophthalmus, into numerous local demes. Genetic and ecological characteristics of demes of adult milkweed beetles occupying two naturally occurring size classes of patches, defined as large and small, were studied in order to describe the effect of patch size variation on local population structure. Allele frequency variance in two of three protein polymorphisms was significantly greater in collections of beetles from an array of 13 small patches when compared to collections from an array of 11 large populations. A multivariate measure of variance using information from all 3 genetic markers confirmed that the small patches displayed greater overall genetic differentiation. This was further quantified by computing an Fst value, combined across loci, of 0.018 for the small patches and 0.004 for the large patches. No significant difference between patch size classes in mean allele frequency was detected. Mark and recapture studies of the adults found in five small and four large patches showed the residence times of adults in small patches to be less than half of those found in large patches. This was interpreted as resulting from higher emigration rates from small patches. It is proposed that greater genetic differentiation is found among demes from smaller patches because smaller patches support smaller population sizes and further because smaller patches act as net exporters of migrants while larger patches act as net migrant importers.


Secretomics reveals gelatinase substrates at the blood-brain barrier that are implicated in astroglial barrier function.
The gelatinases, matrix metalloproteinase 2 (MMP-2) and MMP-9, are key for leukocyte penetration of the brain parenchymal border in neuroinflammation and the functional integrity of this barrier; however, it is unclear which MMP substrates are involved. Using a tailored, sensitive, label-free mass spectrometry-based secretome approach, not previously applied to nonimmune cells, we identified 119 MMP-9 and 21 MMP-2 potential substrates at the cell surface of primary astrocytes, including known substrates (β-dystroglycan) and a broad spectrum of previously unknown MMP-dependent events involved in cell-cell and cell-matrix interactions. Using neuroinflammation as a model of assessing compromised astroglial barrier function, a selection of the potential MMP substrates were confirmed in vivo and verified in human samples, including vascular cell adhesion molecule-1 and neuronal cell adhesion molecule. We provide a unique resource of potential MMP-2/MMP-9 substrates specific for the astroglia barrier. Our data support a role for the gelatinases in the formation and maintenance of this barrier but also in astrocyte-neuron interactions.


Effect of introducing the naked neck gene in a line selected for low residual feed consumption on performance in temperate or subtropical environments.
The aim of this study was to investigate the possibility of combining the naked neck gene with a genetic background that has been optimized for feed efficiency of laying hens at moderate temperature. In 1997, the naked neck gene was introduced into a line selected for low residual feed intake. In 2003, after 6 generations of introgression, 8 males and 56 females heterozygous for the NA*NA mutation were used to generate all 3 genotypes (NA*N/NA*N, NA*NA/NA*N, NA*NA/NA*NA), in 2 hatches, for rearing in Taiwan and France, respectively, at 3-wk intervals. Growth performance, anatomical traits, laying traits, and feed efficiency were recorded in each country. In addition, comb and rectal temperatures were measured in Taiwan. Performance was generally lower and mortality of laying hens was higher in Taiwan (11%) than in France (1%). Genotype x environment interactions were rare: genotype x environment was observed only for body weight at 10 wk of age and was close to significance for egg weight. The laying performance was significantly decreased in Taiwan by about 25%. The naked neck genotype had a negative effect on body weight and a positive effect of clutch length and egg weight. It also affected heat dissipation traits such as wattle length and rectal and surface temperature measurements. There was a clear additive and negative effect of the NA*NA mutation on rectal temperature. Feed intake and residual feed intake were increased in the homozygous carriers of the NA*NA mutation, which may improve heat tolerance of the low residual feed consumption (R-) line. Feed efficiency tended to be better in NA*NA/NA*NA hens in both environments. Thus, the introduction of the NA*NA mutation in the R- background appeared to be favorable from the viewpoint of feed efficiency, but it did not improve laying performance in a subtropical environment. Other factors than temperature, such as diet composition and lighting regimen, may be involved.


Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma.
Angiogenesis has gained wide acceptance as a reliable prognostic factor in several solid tumors. However, to date, experience in pancreatic adenocarcinoma is limited. Specimens from 45 patients radically operated on at our departments from 1988 to 1997 were stained immunohistochemically with the antibodies anti-mutant p53, anti-bcl2, anti Ki67 and anti-CD31. All the slides were reviewed by the same pathologist without knowledge of the patients' outcome. Mutant p53, Ki67 index and vessel count were significantly related to tumoral behaviour and patients' outcome. Among patients with nodal involvement (Stage III), cumulative survival between hypovascular and hypervascular subgroups differed significantly (p = 0.03). Angiogenesis was independent from TNM in assessing the patients'prognosis at COX analysis (p = 0.02). In patients with pancreatic adenocarcinoma, angiogenesis is a reliable indicator of tumor extension, lymph node status and survival. Its evaluation as a common procedure may contribute to a further improvement in the management of these patients and to a proper selection of those who could benefit from different follow-up protocols or adjuvant treatment.


DeepTTA: a transformer-based model for predicting cancer drug response.
Identifying new lead molecules to treat cancer requires more than a decade of dedicated effort. Before selected drug candidates are used in the clinic, their anti-cancer activity is generally validated by in vitro cellular experiments. Therefore, accurate prediction of cancer drug response is a critical and challenging task for anti-cancer drugs design and precision medicine. With the development of pharmacogenomics, the combination of efficient drug feature extraction methods and omics data has made it possible to use computational models to assist in drug response prediction. In this study, we propose DeepTTA, a novel end-to-end deep learning model that utilizes transformer for drug representation learning and a multilayer neural network for transcriptomic data prediction of the anti-cancer drug responses. Specifically, DeepTTA uses transcriptomic gene expression data and chemical substructures of drugs for drug response prediction. Compared to existing methods, DeepTTA achieved higher performance in terms of root mean square error, Pearson correlation coefficient and Spearman's rank correlation coefficient on multiple test sets. Moreover, we discovered that anti-cancer drugs bortezomib and dactinomycin provide a potential therapeutic option with multiple clinical indications. With its excellent performance, DeepTTA is expected to be an effective method in cancer drug design.


Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease.
Cardiovascular disease is a leading cause of morbidity and mortality worldwide, encompassing a variety of cardiac and vascular conditions. Transient receptor potential vanilloid (TRPV) channels, specifically TRPV type 1 (TRPV1) and TRPV type 2 (TRPV2), are relatively recently described channels found throughout the body including within and around the cardiovascular system. They are activated by a variety of stimuli including high temperatures, stretch, and pharmacologic and endogenous ligands. The TRPV1 channel has been found to be an important player in the pathway of the detection of chest pain after myocardial injury. Activation of peripheral TRPV1 via painful stimuli or capsaicin has been shown to have cardioprotective effects, whereas genetic abrogation of TRPV1 results in increased myocardial damage after ischemia and reperfusion injury in comparison to wild-type mice. Furthermore, blood pressure changes have been noted upon TRPV1 stimulation. Similarly, the TRPV2 channel has also been associated with changes in blood pressure and cardiac function depending on how and where the channel is activated. Interestingly, overexpression of TRPV2 channels in the heart induces dystrophic cardiomyopathy; however, stimulation under physiologic conditions leads to improved cardiac function. Probenecid, a TRPV2 agonist, has been studied as a model therapy for its inotropic effects and potential use in the treatment of cardiomyopathy. In this review, we present an up to date account of the growing evidence that supports the study of TRPV1 and TRPV2 channels as targets for therapeutic agents of cardiovascular diseases.


[Imaging of the lower limb veins: when and how?].
Evaluation for possible lower limb deep venous thrombosis (DVT) is a very frequently requested examination. In France, imaging diagnosis is essentially based on complete Doppler sonographic evaluation of both lower limbs. In patients with no co-morbid condition, the D-dimer assay is useful to exclude the possibility of DVT. A positive diagnosis of DVT is based on the lack of venous compressibility and abnormal Doppler signal. The diagnostic accuracy relies on adequate knowledge of vascular anatomy and sufficient training, especially at the calf level. For experienced sonographers, the accuracy is similar at the thigh and calf level. In patients with suspected pulmonary embolus, evaluation of the lower extremity veins is mandatory and frequently performed with CT immediately following CT pulmonary angiography. However, this examination has not been validated yet.


Monitoring the Behavior of Emerging Contaminants in Wastewater-Impacted Rivers Based on the Use of Fluorescence Excitation Emission Matrixes (EEM).
This study investigated the applicability of fluorescence indexes based on the interpretation of excitation emission matrices (EEMs) by PARAFAC analysis and by selecting fluorescence intensities at a priori defined excitation/emission pairs as surrogates for monitoring the behavior of emerging organic compounds (EOCs) in two catchment basins impacted by wastewater discharges. Relevant EOC and EEM data were obtained for a 90 km stretch of the Simeto River, the main river in Sicily, and the smaller San Leonardo River, which was investigated for a 17 km stretch. The use of fluorescence indexes developed by these two different approaches resulted in similar observations. Changes of the fluorescence indexes that correspond to a group of humic-like fluorescing species were determined to be highly correlated with the concentrations of recalcitrant contaminants such as sucralose, sulfamethoxazole and carbamazepine, which are typical wastewater markers in river water. Changes of the fluorescence indexes related to tyrosine-like substances were well correlated with the concentrations of ibuprofen and caffeine, anthropogenic indicators of untreated wastewater discharges. Chemical oxygen demand and dissolved organic carbon concentrations were correlated with humic-like fluorescence indexes. The observed correlations were site-specific and characterized by different regression parameters for every collection event. Caffeine and carbamazepine showed correlations with florescence indexes in the San Leonardo River and in the alluvial plain stretch of the Simeto River, whereas sucralose, sulfamethoxazole and ibuprofen have always been well correlated in all the investigated river stretches. However, when data of different collection events from river stretches where correlations were observed were combined, good linear correlations were obtained for data sets generated via the normalization of the measured concentrations by the average value for the corresponding collection event. These results show that fluorescence based indexes can be used to monitor the behavior of some trace organic contaminants in wastewater impacted rivers and to track wastewater discharges in streams and rivers.


[Alkaline phosphatase isoenzymes and alpha-1-fetoprotein in hepatic neoplasms].
A study was made of possible relations between the placental alkaline phosphatase-isoenzyme (PAP), alpha 1-fetoprotein and liver neoplasia. Ninety-six with various liver diseases were examined, including 10 with primary and 16 with metastatic carcinoma. It was found that both PAP and AFP may be present in a certain percentage of subjects in this pathology. PAP (observed in 30% of cases of primary carcinoma and 43.6% of metastatic forms, as opposed to only 5.6% in cirrhotics) proved much more specific than AFP, which was present in both types of cancer (albeit at much lower concentrations) and also in acute, active chronic and persistent hepatitis, and in cirrhosis of the liver. The theories presented in the relevant literature are discussed in an attempt to explain the "reawakening" of both PAP and AFP, especially in liver neoplasias.


Staphylococcal enterotoxin B as a nonimmunological mast cell stimulus in primates: the role of endogenous cysteinyl leukotrienes.
The immediate-type skin reaction and the emetic response in unsensitized monkeys on challenge with staphylococcal enterotoxin B (SEB) were studied to define the role of cysteinyl leukotrienes (LTs) in the action of the toxin. LY 171883, a selective LTD4/LTE4 receptor inhibitor, antagonized SEB-induced skin reactions and emetic responses completely. Inhibition of prostanoid formation by indomethacin, however, and pretreatment with BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, did not influence these reactions. The generation of endogenous cysteinyl LTs upon intragastric SEB administration was established in vivo. There was a tenfold increase in LTE4, the major biliary cysteinyl LT, and a novel cysteinyl LT metabolite in urine occurred, indicating strongly enhanced LT generation on SEB challenge. These results provide the first evidence that cysteinyl LTs may be important mediators in the pathophysiology of SEB-induced effects, as a model for pseudo-allergic reactions.


Summary of: school bullying and traumatic dental injuries in East London adolescents.
To explore the association between school bullying and traumatic dental injuries (TDI) among 15-16-year-old school children from East London. Data from phase III of the Research with East London Adolescents Community Health Survey (RELACHS), a school-based prospective study of a representative sample of adolescents, were analysed. Adolescents provided information on demographic characteristics, socioeconomic measures and frequency of bullying in school through self-administered questionnaires and were clinically examined for overjet, lip coverage and TDI. The association between school bullying and TDI was assessed using binary logistic regression models. The prevalence of TDI was 17%, while lifetime and current prevalence of bullying was 32% and 11%, respectively. The prevalence of TDI increased with a growing frequency of bullying; from 16% among adolescents who had never been bullied at school, to 21% among those who were bullied in the past but not this school term, to 22% for those who were bullied this school term. However, this association was not statistically significant either in crude or adjusted regression models. There was no evidence of an association between frequency of school bullying and TDI in this sample of 15-16-year-old adolescents in East London.


A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation.
Serotonin is implicated in the etiology of anxiety disorders and in the anxiolytic actions of benzodiazepines. Preclinical studies with 5-HT3 receptor antagonists, including ondansetron, show they have anxiolytic properties and that ondansetron suppresses withdrawal anxiety after abrupt discontinuation of chronic benzodiazepine treatment. We evaluated the efficacy of ondansetron as an adjunctive medication in the discontinuation of benzodiazepines in long-term users. One hundred eight patients who had used alprazolam or lorazepam regularly for > 3 months entered, and 97 completed a randomized double-blind discontinuation treatment program during which they received either ondansetron 2 mg twice daily or placebo and flexibly tapered their benzodiazepine over a 6-week period. There were no significant differences between the patients who had entered and completed treatment. Three weeks postmedication, 63% of the patients discontinued use of benzodiazepine. The percentage of reduction of benzodiazepine daily dosage at all time points in the treatment trial was similar for the ondansetron and placebo groups. Ondansetron had no significant effects on severity of withdrawal symptoms or levels of anxiety. High placebo response may have prevented detection of an ondansetron effect. At 1 year follow-up, 68% of patients reported that they stopped using benzodiazepine. Patient characteristics were more important than ondansetron in tapered benzodiazepine discontinuation.