Notching up another pathway.
The Notch proteins play a vital role in cell fate decisions in both invertebrate and vertebrate development. Careful analysis of this role has led to a model of signalling downstream of these receptors, via the CSL (CBF1, Suppressor of Hairless, Lag-1) family of transcription factors. There have been suggestions, however, that Notch can signal through other pathways. In the current paper, Ramain et al. provide compelling evidence for Notch signalling through a CSL-independent pathway and they demonstrate that the cytoplasmic protein, Deltex, is required for this signal. In addition, they show that Wnt signalling may regulate this Deltex-dependent signal.


The religiosity/spirituality of Latina breast cancer survivors and influence on health-related quality of life.
The study evaluated the association of religiosity/spirituality (R/S) and health-related quality of life (HRQOL) among Latina breast cancer survivors (BCS) in order to determine whether R/S would be positively correlated with HRQOL and whether R/S would significantly influence HRQOL. The cross-sectional study utilized self-report data from 117 Latina BCS survivors. R/S was measured with the Systems of Belief Inventory-15 Revised (SBI-15R) and HRQOL was measured with the Functional Assessment of Cancer Therapy-General (FACT-G). Analyses included calculation of descriptive statistics, t-tests, bivariate correlations, and multivariate analyses. Latina BCS had very high levels of R/S and generally good HRQOL. The SBI-15R total score was positively correlated with FACT-G social well-being (SWB) (r=0.266, p=0.005), relationship with doctor (RWD) (r=0.219, p=0.020), and functional well-being (FWB) (r=0.216, p=0.022). Multivariate analyses revealed that SBI-15R was a significant predictor of FACT-G FWB (p=0.041) and satisfaction with the relationship with the doctor (p=0.050), where higher levels of R/S predicted higher levels of well-being. Latina BCS had very high levels of R/S, which were significantly, positively correlated with dimensions of HRQOL (SWB, FWB, RWD). Furthermore, these high levels of R/S predicted better FWB and satisfaction with the patient-doctor relationship while controlling for potentially confounding variables. Implications are discussed.


One-year aneurysm-sac dynamics are associated with reinterventions and rupture following infrarenal endovascular aneurysm repair.
One-year aneurysm sac changes have previously been found to be associated with mortality and may have the potential to guide personalized follow-up following endovascular aneurysm repair (EVAR). In this study, we examined the association of these early sac changes with long-term reintervention and rupture. We identified all patients undergoing first-time EVAR for intact abdominal aortic aneurysm between 2003 and 2018 in the Vascular Quality Initiative with linkage to Medicare claims for long-term outcomes. We included patients with an imaging study at 1 year postoperatively. Aneurysm sac behavior was defined as per the Society for Vascular Surgery guidelines: stable sac (<5 mm change), sac regression (≥5 mm), and sac expansion (≥5 mm). Outcomes included mortality, reintervention, and rupture within 8 years, which were assessed with Kaplan-Meier methods and multivariable Cox regression analysis. Secondarily, we utilized polynomial spline interpolation to demonstrate the continuous relationship of diameter change to 8-year hazard of reintervention, rupture, or mortality as a composite outcome. Of 31,185 EVAR patients, 16,102 (52%) had an imaging study at 1 year and were included in this study. At 1 year, 44% of sacs remained stable, 49% regressed, and 6.2% displayed expansion. Following risk adjustment, compared with a stable sac at 1 year, sac regression was associated with lower 8-year mortality (49% vs 53%; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99; P = .036), reintervention rate (8.9% vs 15%; HR, 0.58; 95% CI, 0.50-0.68; P < .001), and rupture rate (2.0% vs 4.0%; HR, 0.45; 95%CI, 0.29-0.69; P < .001). Conversely, compared with a stable sac, sac expansion was associated with higher 8-year mortality (64% vs 53%; HR, 1.31; 95% CI, 1.14-1.51; P < .001) and reintervention rate (27% vs 15%; HR, 1.98; 95% CI, 1.57-2.51; P < .001), but similar risk of rupture (7.2% vs 4.0%; HR, 1.61; 95% CI, 0.88-2.96; P = .12). Polynomial spline interpolation demonstrated that, compared with no diameter change at 1 year, increased sac regression was associated with an incrementally lower risk of late outcomes, whereas increased sac expansion was associated with an incrementally higher risk of late outcomes. Following EVAR, compared with a stable sac at 1-year imaging, sac regression and expansion are associated with a lower and higher risk respectively of long-term mortality, reinterventions, and ruptures. Moreover, the amount of regression or expansion seems to be incrementally associated with these late outcomes, too. Future studies are needed to determine how to improve 1-year sac regression, and whether it is safe to extend follow-up intervals for patients with regressing sacs.


High-fat diet affects measures of skeletal muscle contractile performance in a temperature-specific manner but does not influence regional thermal sensitivity.
The present study examined whether high-fat diet (HFD) consumption for 20 weeks had a temperature-specific effect on the contractile performance and regional thermal sensitivity of isolated mouse soleus and diaphragm muscle. Four-week-old female CD-1 mice were randomly selected to consume either a standard laboratory diet or a standard laboratory diet in conjunction with a HFD for 20 weeks. Peripheral soleus and core diaphragm were isolated from each animal and maximal isometric force and work loop power were assessed at 20, 28, 35 and 40°C. Increasing temperature to 35°C resulted in greater isometric stress, lower activation and relaxation time, and higher work loop power in both muscles. A further increase in temperature to 40°C did not affect isometric force but increased work loop power output of the soleus. Conversely, isometric force of the diaphragm was reduced and work loop power maintained when temperature was increased to 40°C. HFD consumption resulted in greater isometric force and absolute work loop power of the soleus and reduced isometric stress of the diaphragm, effects that were less apparent at lower temperatures. When the relationship between temperature and each measure of contractile function was examined by linear regression, there was no difference in slope between the control or HFD groups for either the soleus or diaphragm. These results indicate that whilst contractile function initially increases with temperature, the temperature to elicit maximal performance is muscle and contractile mode specific. Furthermore, HFD effects on contractile function are temperature specific, but HFD does not influence the relationship between temperature and performance.


[Pharmacokinetic, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology. Study group of cefuzonam in the field of obstetrics and gynecological infections].
A multi-center open study was conducted to investigate cefuzonam (CZON, L-105) regarding to its pharmacokinetic, bacteriological and clinical aspects in the field of obstetrics and gynecology with the participation of 31 medical institutions and the related facilities. The results are summarized as follows. 1. Peak MICs of CZON for Staphylococcus aureus, coagulase (-) staphylococci, Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis group, Peptostreptococcus spp. isolated from obstetrical and gynecological infections with relatively high frequencies were 0.39, 0.20, 0.024, 0.024-0.05, 12.5, 0.20 microgram/ml, respectively, with an inoculum size of 10(6) CFU/ml. 2. When 1 g of CZON was given through bolus injection, the maximum concentration (Cmax) of CZON in pelvic dead space exudate was 18.7 micrograms/ml at 60.9 minutes (Tmax) after the injection; Cmax's in all female genital tissues were observed at 0.6-27.9 minutes and ranged from 11.9-26.3 micrograms/g. The Cmax 8.3 micrograms/ml, in the pelvic dead space exudate was noted at 97.0 minutes after the end of the intravenous drip infusion of 1 g over 1 hour, and Cmax's in genital tissues were 14.3-30.0 micrograms/g at the end of infusion. With 1 hour drip infusion of 2 g, Cmax's in genital tissues were 35.0-53.9 micrograms/g at the end of infusion. 3. The clinical efficacy of CZON was evaluated in 206 evaluable patients with obstetric and gynecologic infections. Efficacy rates classified by types of infections were 97.1% (67/69) for intrauterine infections, 81.6% (31/38) for intrapelvic infections, 91.8% (45/49) for adnexitis, 95.2% (20/21) for infections of the external genital organs and 86.2% (25/29) for other infections. 4. Side effects were observed in 7 of the 262 patients: eruption in 6 cases, itching in 2, diarrhea in 1. Abnormal laboratory test values were noted in 9 of the 256 patients. Most of them were slight elevation of hepatic function values. CZON showed satisfactory clinical efficacy and potent antibacterial activity, hence it appears that CZON will be a very useful antibiotic for obstetric and gynecologic infections.


Cohabitation as a determinant of adaptive and innate immune cell profiles: Findings from the Health and Retirement Study.
Non-genetic factors are important but poorly understood determinants of immune profiles. Age and Cytomegalovirus (CMV) infection remain two well documented non-genetic determinants of the immune profile. Recently, one study identified cohabitation in the same household as an important determinant of immune profiles. We used immunophenotyping data from the Health and Retirement Study (HRS) to evaluate the association between cohabitation and the adaptive (subsets of T-cells, B-cells) and innate immune profiles (subsets of monocytes, natural killer cells and neutrophils). We compared adaptive and innate immune cell profiles using immunophenotyping data from 1184 same-household pairs (cohabitating partners) to 1184 non-household pairs to evaluate the association between cohabitation and adaptive immune cell profiles. We used data from 1737 same-household pairs and 1737 non-household pairs to evaluate the association between cohabitation and innate cell profiles. Household and non-household pairs were matched on age (±2years), educational background and race/ethnicity to minimize confounding due to these factors. The adaptive immune cells and innate immune cell profiles were compressed to two coordinates using multidimensional scaling (MDS). The Euclidean distances between same-household pairs were compared to the distances between non-household pairs for the adaptive and innate cell profiles separately using two sample independent t-tests. We also performed additional adjustment for age and BMI differences, CMV serostatus and smoking concordance/discordance status among household members. For adaptive immune cell profiles, the mean Euclidean distance between same-household pairs was 4% lower than the non-household pairs (p = 0.03). When stratified by concordance for CMV serostatus among household pairs, the Euclidean distance was significantly lower by 8% in the same-household pairs as compared to non-household pairs among those who were discordant for CMV serostatus (p = 0.01) and among same-household pairs who were CMV seronegative (p = 0.02) after covariate adjustment. The mean Euclidian distance between same-household pairs was also 8% lower than non-household pairs for the innate immune cell profiles (p-value <0.0001) and this difference remained consistent across all strata of CMV infection. This study confirms that cohabitation is associated with similarity in immune cell profiles. The differential effects of cohabitation on the adaptive and innate immune profiles suggest that further studies into the common environmental factors that influence individual immune cell subsets need to be evaluated in greater detail.


[Simultaneous determination of five saponins in Bupleuri Radix by HPLC-DAD dual wavelength method].
Epoxy ether type and isophthalene type saponin are the main saponins of Bupleurum chinense. However,due to the difference of their UV spectrum,there is no quantitative method for simultaneous determination of these two kinds of saponins. In this paper,a dual-wavelength high performance liquid chromatography(HPLC) was developed for simultaneous determination of five saponins in epoxidized ether(saikosaponin a,c,d) and isosorbide type(saikosaponin b1,b2). The mobile phase was eluted with acetonitrile-water(0.1% phosphoric acid) gradient at a column temperature of 30 °C and a flow rate of 1.0 mL·min⁻¹. The detection wavelengths were 208 nm for saikosaponins a,c, and d, and 254 nm for saikosaponins b₁ and b₂. The results showed that the separation of five kinds of saikosaponin was good, with the linear range of 9.70-1 935.00(r=0.999 4),8.20-1 380.00(r=0.999 3),6.90-1 640.00(r=0.999 0),5.25-630.00(r=0.999 4), and 5.15-618.00 mg·L⁻¹(r=0.999 5), respectively. The average recoveries were 97.70%-100.2% and the RSD was less than 3%(n=6). The method is simple,rapid and reproducible. It can be used for the determination of five kinds of saikosaponins in B. chinense.


Plasma dopamine in regulation of canine renal blood flow.
Studies were performed in pentobarbital-anesthetized dogs to determine whether circulating plasma dopamine (DA) is involved in renal blood flow (RBF) regulation. During graded reductions in renal perfusion pressure (RPP), total renal venous (RV) DA content significantly increased at RPPs below the autoregulatory range. The RBF response to decrements in RPP was also examined during control, infusion of DA (1.2 micrograms.kg(-1).min(-1)ia), and after DA receptor blockade by SCH 23390 (30 micrograms/kg iv). During DA infusion, autoregulation was still evident over the same RPPs, although at higher flow rates. At pressures below the autoregulatory range, RBF decreased linearly and the autoregulatory curve merged with control at 50 mmHg. After SCH 23390, autoregulation ceased at a higher RPP than during control, and RBF was significantly less than control rates at pressures of 80 mmHg and below. To elucidate reasons for this latter response, reductions in RPP were repeated before and after administration of both prazosin (0.1 mg/kg iv) and SCH 23390. The results indicated that RBF rates were not different from control at any RPP. Further, prazosin alone did not alter renal autoregulation but significantly increased RBF at RPP below the autoregulatory range. Thus these results indicate that dopamine does not participate in RBF control at pressures above the inflection point for the lowest limit of RBF autoregulation but may be released at lower RPP to act as a vasodilator agent to oppose alpha-adrenoceptor-mediated reductions in RBF. Moreover, tonic DA receptor activation may influence the setting of the lower limit of canine RBF autoregulation.


Mapping Hydration Dynamics around a β-Barrel Protein.
Protein surface hydration is fundamental to its structure, flexibility, dynamics, and function, but it has been challenging to disentangle their ultimate relationships. Here, we report our systematic characterization of hydration dynamics around a β-barrel protein, rat liver fatty acid-binding protein (rLFABP), to reveal the effect of different protein secondary structures on hydration water. We employed a tryptophan scan to the protein surface one at a time and examined a total of 17 different sites. We observed three types of hydration water relaxation with distinct time scales, from hundreds of femtoseconds to a hundred picoseconds. We also examined the anisotropy dynamics of the corresponding tryptophan side chains and observed two distinct relaxations from tens to hundreds of picoseconds. Integrating our previous findings on α-helical proteins, we conclude the following: (1) The hydration dynamics is highly heterogeneous around the protein surface of both α-helical and β-sheet proteins. The outer-layer water of the hydration shell behave like a bulk and relaxes in hundreds of femtoseconds. The inner-layer water collectively relaxes in two time scales, reorientation motions in a few picoseconds and network restructuring in tens to a hundred picoseconds. (2) The hydration dynamics are always faster than local protein relaxations and in fact drive the protein fluctuations on the picosecond time scale. (3) The hydration dynamics in general are more retarded around β-sheet structures than α-helical motifs. A thicker hydration shell and a more rigid interfacial hydration network are observed in the β-sheet protein. Overall, these findings elucidate the intimate relationship between water-protein interactions and dynamics on the ultrafast time scale.


Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor.
Although clinical and experimental studies have long suggested a role for the renin-angiotensin system (RAS) in the regulation of erythropoiesis, the molecular basis of this role has not been well understood. We report here that transgenic mice carrying both the human renin and human angiotensinogen genes displayed persistent erythrocytosis as well as hypertension. To identify the receptor molecule responsible for this phenotype, we introduced both transgenes into the AT1a receptor null background and found that the hematocrit level in the compound mice was restored to the normal level. Angiotensin II has been shown to influence erythropoiesis by two means, up-regulation of erythropoietin levels and direct stimulation of erythroid progenitor cells. Thus, we conducted bone marrow transplantation experiments and clarified that AT1a receptors on bone marrow-derived cells were dispensable for RAS-dependent erythrocytosis. Plasma erythropoietin levels and kidney erythropoietin mRNA expression in the double transgenic mice were significantly increased compared with those of the wild-type control, while the elevated plasma erythropoietin levels were significantly attenuated in the compound mice. These results provide clear genetic evidence that activated RAS enhances erythropoiesis through the AT1a receptor of kidney cells and that this effect is mediated by the elevation of plasma erythropoietin levels in vivo.


Cloning and sequencing of the ribosomal RNA genes in maize: the 17S region.
The maize genes for the 17S, 5.8S, and 26S ribosomal RNAs (rRNAs) are located on chromosome 6 and consist of 9-kb sequences repeated about 5,000-10,000 times per 2C. One of these sequences was isolated from a lambda library containing maize Eco RI genomic segments. The sequence of the small-subunit (17S) RNA was determined using the M13 shotgun-dideoxy sequencing approach. The maize sequence was compared with nuclear rRNAs from yeast, Xenopus, and rat. Using these sequences, it is possible to identify tentatively the start and the end points of the sequence of the maize nuclear small subunit rRNA. This RNA has a length of 1809 nucleotides. The alignment of all four sequences for maximal homology allows us to identify regions within the rRNA that have been conserved during eukaryotic evolution.


Locating Carbon-Carbon Double Bonds in Unsaturated Phospholipids by Epoxidation Reaction and Tandem Mass Spectrometry.
The presence of carbon-carbon double bonds (C═Cs) in unsaturated phospholipids is closely related to lipid conformations and physiochemical activities. Previously, we have demonstrated that epoxidation reaction facilitated by low-temperature plasma (LTP) enabled the structural analysis of unsaturated fatty acids (FAs). Epoxidation of the C═C leads to the production of an epoxide, which can be easily cleaved via collision-induced dissociation (CID) to produce diagnostic ions indicative of the C═C bond locations in FAs. In this work, we further developed this method for analysis of phospholipids. Tandem mass spectrometry analysis with epoxidation reaction was performed in both positive and negative ion mode to analyze phosphatidylcholines (PCs), phosphatidic acids (PAs), phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs), and phosphatidylinositols (PIs). The developed method was applied in a shotgun lipidomics approach to characterize phospholipids in a bovine liver extract.


[Flexor carpi radialis tendon rupture following percutaneous osteosynthesis of the scaphoid: a case report].
We present a rare complication of percutaneous osteosynthesis of a scaphoid fracture. A 19-year-old professional handballer presented with a fracture of the scaphoid classified B2 according to the Herbert classification: the fracture was fixed with a percutaneous screw. The fracture was united by six weeks despite resumption of training eight days postoperatively. Subsequently, the patient presented with pain over the flexor carpi radialis (FCR) tendon together with reduction of wrist flexion strength suggested an FCR tendonitis. A CT scan with injection eliminated the diagnosis of non-union and showed protrusion of the distal end of the screw. After the failure of conservative treatment (corticosteroid injection), removal of the screw and synovectomy of the FCR were scheduled. During the procedure, attrition of the FCR tendon with scar tissue and metal inclusions in its fibres were observed. A visual examination of the screw's distal end showed a distortion of its hexagonal outline due to hammering, leading to metal projection likely to have caused the FCR tendon's attrition. We recommend the systematic burying of these canulated screws as well as changing any screw damaged during its insertion.


Are oral and maxillofacial surgery residents being adequately trained to care for pediatric patients?
To evaluate whether current oral and maxillofacial surgery (OMS) residents are receiving adequate training and experience to perform specific surgical procedures and anesthesia for pediatric patients. A 17-question survey was sent electronically to fellows of the American Academy of Craniomaxillofacial Surgeons. Descriptive data for individual surgeons, their associated residency programs, and the quantity of specific pediatric procedures they performed were collected. Resident case load for inpatient and outpatient procedures and overall experience in medical, surgical, and anesthetic management of pediatric OMS patients were explored. Surveys were sent to 110 active fellows; 64 completed the questionnaire (58%). There were 59 male fellows and 5 female fellows, with a mean age of 50.4 years. Of those, 68.8% practice in an academic setting. Specifically, 93.8% take after-hours emergency calls covering adult and pediatric patients and 98.4% have admitting privileges at a children's hospital or a pediatric unit in an adult hospital. Their affiliated residency programs include required rotations in pediatrics or pediatric subspecialties. In their opinion, >90% of graduating OMS residents have the appropriate skill set to perform dentoalveolar procedures, outpatient anesthesia, orthognathic procedures, and alveolar bone grafts. However, residents have limited ability to reconstruct pediatric ramus-condyle unit with a costochondral graft. Results of this study indicate that, in the opinion of the respondents, graduates of OMS residency programs have adequate training to perform dentoalveolar procedures, outpatient anesthesia, orthognathic surgery, and alveolar bone grafts in pediatric procedures, but have limited experience with reconstruction of pediatric ramus-condyle unit via costochondral graft.


CRISPR/Cas System: The Accelerator for the Development of Non-nucleic Acid Target Detection in Food Safety.
Non-nucleic acid targets have posed a serious challenge to food safety. The detection of non-nucleic acid targets can enable us to monitor food contamination in a timely manner. In recent years, the CRISPR/Cas system has been extensively explored in biosensing. However, there is a lack of a summary of CRISPR/Cas-powered detection tailored to non-nucleic acid targets involved in food safety. This review comprehensively summarizes the recent advances on the construction of CRISPR/Cas-powered detection and the promising applications in the field of food safety related non-nucleic acid targets. The current challenges and futuristic perspectives are also proposed accordingly. The rapidly evolving CRISPR/Cas system has provided a powerful propellant for non-nucleic acid target detection via integration with aptamer and/or DNAzyme. Compared with traditional analytical methods, CRISPR/Cas-powered detection is conceptually novel, essentially eliminates the dependence on large instruments, and also demonstrates the capability for rapid, accurate, sensitive, and on-site testing.


Cholangiocarcinoma following external beam radiotherapy: A report of two cases.
Cholangiocarcinoma (CCA) is a relatively rare primary malignancy, with established risk factors that include primary sclerosing cholangitis, choledochal cysts and hepatolithiasis. In the present study, two cases of CCA, which occurred following abdominal external beam radiotherapy (EBRT) for non-Hodgkin's lymphoma, are reported. Case 1 and 2 were diagnosed with cholangiocarcinoma 30 and 4 years following treatment with combined chemotherapy and abdominal radiotherapy treatment, respectively. The patients received chemotherapy as treatment of cholangiocarcinoma; however, whilst their symptoms improved, they succumbed within 12 and 2 months respectively following the diagnosis with cholangiocarcinoma. Currently, the association between radiation exposure and hepatobiliary malignancy remains unclear, however, we hypothesize that biliary epithelium sensitivity to ionizing radiation may have contributed to the etiology of the secondary malignancies observed in these two patients. This study indicates that patients treated with abdominal EBRT may benefit from a heightened index of suspicion and more intensive surveillance for secondary biliary malignancies.


Entanglement concentration using quantum statistics.
We propose an entanglement concentration scheme which uses only the effects of quantum statistics of indistinguishable particles. This establishes the fact that useful quantum information processing can be accomplished by quantum statistics alone. Because of the basis independence of statistical effects, our protocol requires less knowledge of the initial state than most entanglement concentration schemes. Moreover, no explicit controlled operation is required at any stage.


Hypoxia sensing and pathways of cytosolic Ca2+ increases.
Oxygen-sensing and reactivity to changes in the concentration of oxygen is a fundamental property of cellular physiology. This central role is determined, mainly, by, to the fact that oxygen represents the final acceptor of electrons, derived from the normal cellular metabolism, at the end of the mitochondrial respiratory chain. Despite significant advances in molecular characterization of various oxygen-sensitive processes, the nature of the oxygen-sensor molecules and the mechanisms that link sensors to effects remains unclear. One such controversy is about the role and nature of reactive oxygen species (ROS) changes during hypoxia. Irrespective of the mechanisms of oxygen sensing, one of the constant early responses to hypoxia in almost all cell types is an increase in intracellular Ca2+ ([Ca2+]i). In many instances, this increase is mediated by the activation of various plasma membrane Ca2+ conductances. Some of these channels have specific Ca2+ permeability (e.g. voltage-operated Ca2+ channels), whereas others have non-specific cation conductances and are activated by a variety of ligands (ligand-operated channels). In the last decade, a large superfamily of channels with significant Ca2+ permeability has been progressively identified and characterised: the TRP channels. Through their properties, some groups of the TRP channels provide a link to the other hypoxia-activated mechanism of [Ca2+]i increase: the release of Ca2+ from intracellular Ca2+ stores. Since the [Ca2+]i signals, depending on their localization and intensity, are important regulators of the subsequent cellular responses to hypoxia, a deeper understanding of the mechanisms through which hypoxia regulate the activity of these pathways that increase intracellular Ca2+ could point the way towards the development of new therapeutic approaches to reduce or suppress the pathological effects of cellular hypoxia, such as those seen in stroke or myocardial ischemia.


[Economic evaluation of radiotherapy: methods and results].
The cost of radiotherapy, which concerns 150,000 new patients yearly in France has been estimated 1700 euros per patients in this country, 50% lower than the European average. Economic evaluations of radiotherapy have related the cost of either curative or palliative treatment to the medical outcome. For lung, rectal, breast cancer and bone metastases of prostate cancer, radiation therapy prolongs life by an estimated 6 to 10 months. The cost effectiveness ranges from 5,000 to 25,000 euros per life year gained.


Analysis of Pelagia noctiluca proteome Reveals a Red Fluorescent Protein, a Zinc Metalloproteinase and a Peroxiredoxin.
Pelagia noctiluca is the most venomous jellyfish in the Mediterranean Sea where it forms dense blooms. Although there is several published research on this species, until now none of the works has been focused on a complete protein profile of the all body constituents of this organism. Here, we have performed a detailed proteomics characterization of the major protein components expressed by P. noctiluca. With that aim, we have considered the study of jellyfish proteins involved in defense, body constituents and metabolism, and furthered explore the significance and potential application of such bioactive molecules. P. noctiluca body proteins were separated by1D SDS-PAGE and 2DE followed by characterization by nanoLC-MS/MS and MALDI-TOF/TOF techniques. Altogether, both methods revealed 68 different proteins, including a Zinc Metalloproteinase, a Red Fluorescent Protein (RFP) and a Peroxiredoxin. These three proteins were identified for the first time in P. noctiluca. Zinc Metalloproteinase was previously reported in the venom of other jellyfish species. Besides the proteins described above, the other 65 proteins found in P. noctiluca body content were identified and associated with its clinical significance. Among all the proteins identified in this work we highlight: Zinc metalloproteinase, which has a ShK toxin domain and therefore should be implicated in the sting toxicity of P. noctiluca.; the RFP which are a very important family of proteins due to its possible application as molecular markers; and last but not least the discovery of a Peroxiredoxin in this organism makes it a new natural resource of antioxidant and anti-UV radiation agents.


Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies.
The aim of this meta-analysis was to assess whether tranexamic acid (TXA) therapy for adult cardiac surgery is associated with an increase in the risk of seizures, and we performed a meta-analysis of randomized controlled trials (RCTs) and non-randomized observational studies. MEDLINE and EMBASE were searched through December 2016 using PubMed and OVID. Eligible studies were RCTs and non-randomized observational studies on TXA versus control (no TXA, placebo, or active control such as low-dose TXA, aprotinin, and epsilon aminocaproic acid) enrolling adult patients undergoing cardiac surgery and reporting the postoperative incidence of seizures as an outcome. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic odds ratios (ORs) in the random-effects model. Of 90 potentially relevant articles screened initially, 16 reports of eligible studies were identified and included. A pooled analysis of all 16 studies (enrolling 45,235 patients) demonstrated that TXA therapy was associated with a statistically significant increase in the seizures incidence (OR=4.13; 95% CI: 2.59 to 6.57; P<0.00001). A subgroup analysis indicated a statistically significant increase in the seizures incidence with TXA therapy in all subgroups of 5 RCTs, 5 adjusted observational studies, and 6 unadjusted observational studies with no statistically significant subgroup differences (P=0.36; I2=1.5%). The results of the present meta-analysis of 16 studies enrolling 45,235 patients confirmed that TXA therapy for adult cardiac surgery is associated with a 4.1-fold increase in the risk of seizure.


The interplay of exercise heart rate and blood pressure as a predictor of coronary artery disease and arterial hypertension.
Delayed blood pressure (BP) and heart rate (HR) decline at recovery post-exercise are independent predictors of incident coronary artery disease (CAD). Delayed BP recovery and exaggerated BP response to exercise are independent predictors of future arterial hypertension (AH). This study sought to examine whether the combination of two exercise parameters provides additional prognostic value than each variable alone. A total of 830 non-CAD patients (374 normotensive) were followed for new-onset CAD and/or AH for 5 years after diagnostic exercise testing (ET). At the end of follow-up, patients without overt CAD underwent a second ET. Stress imaging modalities and coronary angiography, where appropriate, ruled out CAD. New-onset CAD was detected in 110 participants (13.3%) whereas AH was detected in 41 former normotensives (11.0%). The adjusted (for confounders) relative risk (RR) of CAD in abnormal BP and HR recovery patients was 1.95 (95% confidence interval [CI], 1.28-2.98; P=.011) compared with delayed BP and normal HR recovery patients and 1.71 (95% CI, 1.08-2.75; P=.014) compared with normal BP and delayed HR recovery patients. The adjusted RR of AH in normotensives with abnormal BP recovery and response was 2.18 (95% CI, 1.03-4.72; P=.047) compared with delayed BP recovery and normal BP response patients and 2.48 (95% CI, 1.14-4.97; P=.038) compared with normal BP recovery and exaggerated BP response individuals. In conclusion, the combination of two independent exercise predictors is an even stronger CAD/AH predictor than its components.


Primary fixation in osmium-potassium ferrocyanide: the staining of glycogen, glycoproteins, elastin, an intranuclear reticular structure, and intercisternal trabeculae.
Primary fixation in an osmium-potassium ferrocyanide (K4Fe(CN)6) mixture combines selective fixation, staining, and extraction of various cellular components; membranes, glycogen, glycoproteins, and elastin are preserved and stained. An intranuclear reticular structure that is composed of 3-6 nm fibers and permeates the entire nucleus, except for the nuclear pores, is demonstrated by electron microscopic examination of tissues prepared in an osmium-potassium ferrocyanide fixative. Condensations of the reticulum parallel the distribution of heterochromatin in interphase nuclei. This preparative procedure also reveals a network of trabeculae that are associated with the cisternae of rough endoplasmic reticulum and connect the parallel cisternae in hepatocytes, plasmacytes, neurons, and pancreatic ancinar cells. The intercisternal trabeculae are associated with both free and bound ribosomes.


Low Carotid Artery Wall Shear Stress is Associated with Significant Coronary Artery Disease in Patients with Chest Pain.
To investigate the relationships among carotid wall shear stress (WSS), carotid intima-media thickness (IMT), and total plaque area (TPA) using ultrasound (US) in the common carotid artery (CCA) in patients with suspected coronary artery disease (CAD). Carotid artery US was performed in 950 patients with suspected CAD, and mean IMT, TPA, and hemodynamic parameters of CCA, including peak and mean WSS, were measured. We analyzed the carotid parameters according to the presence of CAD and the predictive values of WSS and TPA for the presence of significant CAD. Compared with patients without CAD (n=667), patients with CAD (n=283) demonstrated significantly higher mean IMT (0.66 vs. 0.74 mm, p < 0.001), TPA (0.13 vs. 0.20 cm(2), p=0.002), and beta stiffness index (5.12 vs. 5.60, p=0.045) and lower mean WSS (2.59 vs. 2.23 dyne/cm(2), p < 0.001). Mean WSS revealed significant negative correlations with the beta stiffness index (r=-0.116, p < 0.001), mean IMT (r=-0.193, p=0.007), and TPA (r =-0.296, p < 0.001). Mean WSS, mean IMT and TPA revealed significant difference with respect to CAD severity (for all p < 0.001). Age [OR, 1.038 (95% CI, 1.010-1.066), p=0.007], diabetes mellitus [1.606 (1.194-1.807), p= 0.011], smoking [1.758 (1.564-1.866), p < 0.001], carotid TPA [2.615 (1.320-5.183), p=0.006], and mean WSS [0.554 (0.371-0.838), p=0.005] were significant CAD predictors. In patients with chest pain, low local shear stress and high plaque burden in the carotid arteries were significant CAD predictors. These findings indicate that carotid WSS has a role as an index of atherosclerosis and serves as a predictor of significant coronary atherosclerosis.


In-vitro activity of LY 146032, a novel cyclic lipopeptide, alone and in combination with gentamicin or tobramycin against enterococci.
The in-vitro activity of LY 146032, a novel cyclic lipopeptide and the effect of the combination of LY 146032 and gentamicin or tobramycin against 25 strains of enterococci isolated from blood cultures were studied. All strains of enterococci were inhibited by less than or equal to 2 mg/l LY 146032. The minimal inhibitory concentrations and minimal bactericidal concentrations were within one dilution. In the time-kill study, there was slow bactericidal activity. Complete killing of 10(7) cfu/ml of enterococci at 48 h by LY 146032 alone occurred with two strains. There was synergism between LY 146032 and gentamicin or tobramycin; complete killing at 24 h and 48 h occurred with many strains. No antagonism was demonstrated.


The tomato calcium-permeable channel 4.1 (SlOSCA4.1) is a susceptibility factor for pepino mosaic virus.
The hyperosmolality-gated calcium permeable channel 4.1 (OSCA4.1) belongs to an evolutionarily conserved small family of mechano-sensitive channels. OSCA members may represent key players in plant resistance to drought and to pathogen infection but are scarcely studied. After screening for resistance to pepino mosaic virus (PepMV) a collection of 1000 mutagenized tomato families, we identified a mutant showing no symptoms and reduced virus accumulation. Resistance was mapped to chromosome 2 between positions 46 309 531 to 47 044 163, where a missense mutation caused the putative truncation of the OSCA4.1 protein. A CRISPR/Cas9 slosca4.1 mutant was resistant to PepMV, but not to tobacco mosaic virus or potato virus X. Inoculation of mutant and wild type tomato protoplasts showed that resistance was expressed in single cells, suggesting a role for SlOSCA4.1 in early viral function(s); congruently, SlOSCA4.1 re-localized to structures reminiscent of viral replication complexes. We propose that SlOSCA4.1 contributes to the correct regulation of the Ca2+ homeostasis necessary for optimal PepMV infection. PepMV is a pandemic virus that causes significant losses in tomato crops worldwide. In spite of its importance, no tomato-resistant varieties have been deployed yet; the mutant identified here has great potential to breed tomato varieties resistant to PepMV.


Control of intestinal allograft rejection by FTY720 and costimulation blockade.
The clinical application of small bowel transplantation (SBTx) is hampered by its pronounced immunogenicity. In this study we examined the effects of the novel immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in a stringent mouse model of SBTx. SBTx was performed in mice with a full MHC mismatch (donors: C3H=H-2(k); recipients: C57BL/6=H-2(b)). Recipients were divided into four groups: 1, untreated group; 2, MR1 monotherapy (500 microg IV on days 0, 2, 4, and 7); 3, FTY720 monotherapy (1 mg/kg body weight PO for 14 consecutive days after transplantation); 4, FTY720 plus MR1-treated group. Graft rejection grades were assessed by H&E staining. Graft mesenteric lymph nodes (MLNs), Peyer's patches (PPs), as well as intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were analyzed by flow cytometry and three-color immunofluorescence staining. Neither FTY720 nor MR1 monotherapy was efficient in preventing the rejection of mouse intestinal allografts, whereas FTY720 plus MR1 profoundly inhibited the rejection response at the 14th posttransplant day. The infiltration of host lymphocytes was reduced in graft MLNs, PPs, IELs, and LPLs by FTY720 therapy. FTY720 plus MR1 inhibited host CD8(+) T-cell infiltration in graft LPLs when compared with grafts treated with FTY720 only. Additionally, two subpopulations, CD11b(+high) Gr1(-) and CD11b(+intermediate) Gr1(+) cells, were decreased in FTY720-treated grafts. FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse model by preventing the infiltration of host lymphocytes, particularly of CD8(+) cells.


Synthetic Mechanisms in the Formation of SnTe Nanocrystals.
Infrared active colloidal semiconducting nanocrystals (NCs) are important for applications including photodetectors and photovoltaics. While much research has been conducted on nanocrystalline materials such as the Pb and Hg chalcogenides, less toxic alternatives such as SnTe have been far less explored. Previous synthetic work on SnTe NCs have characterized photophysical properties of the nanoparticles. This study focuses on understanding the fundamental chemical mechanisms involved in SnTe NC formation, with the aim to improve synthetic outcomes. The solvent oleylamine, common to all SnTe syntheses, is found to form a highly reactive, heteroleptic Sn-oleylamine precursor that is the primary molecular Sn species initiating NC formation and growth. Further, the capping ligand oleic acid (OA) reacts with this amine to produce tin oxide (SnOx), facilitating the formation of an NC SnOx shell. Therefore, the use of OA during synthesis is counterproductive to the formation of stoichiometric SnTe nanoparticles. The knowledge of chemical reaction mechanisms creates a foundation for the production of high-quality, unoxidized, and stoichiometric SnTe NCs.


EFFICACY AND SAFETY OF BAN HUANG ORAL LIQUID FOR TREATING BOVINE RESPIRATORY DISEASES.
Ban Huang oral liquid was developed as a veterinary compound preparation by the Lanzhou Institute of Husbandry and Pharmaceutical Sciences of the Chinese Academy of Agricultural Sciences (CAAS). The purpose of this study was to determine whether the oral liquid preparation of traditional Chinese medicine, Ban Huang, is safe and effective for treating respiratory diseases in cattle. Acute oral toxicity experiments were conducted in Wistar rats and Kunming mice via oral administration. The minimum inhibitory concentration of the drug against Mycoplasma bovis in vitro with the double dilution method was 500 mg/mL, indicating good sensitivity. The results of laboratory pathogen testing, analysis of clinical symptoms, and analysis of pathological anatomy were combined to diagnose bovine respiratory diseases in 147 Simmental cattle caused by mixed infections of M. bovis, bovine respiratory syncytial virus, bovine parainfluenza virus type 3, and Mannheimia haemolytica. These cattle were randomly divided into three groups: drug treatment group 1 (treated via Tilmicosin injection), drug treatment group 2 (treated with Shuang Huang Lian oral liquid combined with Tilmicosin injection), and drug treatment group 3 (treated with Ban Huang oral liquid combined with Tilmicosin injection). Treatment effects were observed within 7 days. The results showed no toxicity and a maximum tolerated dose greater than 20 g/kg BW. For the 87 cattle in drug-treatment group, the cure rate was 90.80%, whereas the response rate was 94.25%. The cure rate of drug treatment group was increased by 14.13% in comparison with that of drug control group 1 and by 7.47% in comparison with that of drug control group 2 (both P < 0.05). This study demonstrates that Ban Huang oral liquid is a safe and effective treatment for bovine respiratory diseases, especially for mixed infection caused by M. bovis, bacteria, and viruses.


Adoptive transfer of genetically modified Wilms' tumor 1-specific T cells in a novel malignant skull base meningioma model.
Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat meningiomas. The goal of this study was to investigate the potential of build-in short interfering RNA-based Wilms' tumor protein (WT1)-targeted adoptive immunotherapy in a reproducible mouse model of malignant skull base meningioma that we recently established. We compared WT1 mRNA expression in human meningioma tissues and gliomas by quantitative real-time reverse-transcription polymerase chain reaction. Human malignant meningioma cells (IOMM-Lee cells) were labeled with green fluorescent protein (GFP) and implanted at the skull base of immunodeficient mice by using the postglenoid foramen injection (PGFi) technique. The animals were sacrificed at specific time points for analysis of tumor formation. Two groups of animals received adoptive immunotherapy with control peripheral blood mononuclear cells (PBMCs) or WT1-targeted PBMCs. High levels of WT1 mRNA expression were observed in many meningioma tissues and all meningioma cell lines. IOMM-Lee-GFP cells were successfully implanted using the PGFi technique, and malignant skull base meningiomas were induced in all mice. The systemically delivered WT1-targeted PBMCs infiltrated skull base meningiomas and significantly delayed tumor growth and increased survival time. We have established a reproducible mouse model of malignant skull base meningioma. WT1-targeted adoptive immunotherapy appears to be a promising approach for the treatment of difficult-to-treat meningiomas.


Does Cognitive Broadening Reduce Anger?
Past theory and research have suggested that motivationally intense affective states narrow cognitive scope. Research has also suggested manipulations that broaden cognitive scope reduce responses to appetitive positive affective stimuli and disgusting stimuli, thus suggesting that cognitive broadening reduces motivational intensity. This led to the hypothesis that cognitive broadening would reduce the approach-motivated negative emotion of anger. Seven studies assessed the effect of cognitive broadening on reported trait anger, state anger, attitudes toward anger, attributions of anger to ambiguous pictures, and accessibility of aggressive words. Results from individual studies found mixed support for these predictions. A meta-analysis, however, suggested a small but significant effect on trait anger/aggression and attitudes toward anger across studies. These results may indicate that cognitive scope, as manipulated in these studies, has a small effect on anger-related responses. Discussion speculates on potential explanations of these findings, and their importance for informing future research.


Short reads from honey bee (Apis sp.) sequencing projects reflect microbial associate diversity.
High throughput (or 'next generation') sequencing has transformed most areas of biological research and is now a standard method that underpins empirical study of organismal biology, and (through comparison of genomes), reveals patterns of evolution. For projects focused on animals, these sequencing methods do not discriminate between the primary target of sequencing (the animal genome) and 'contaminating' material, such as associated microbes. A common first step is to filter out these contaminants to allow better assembly of the animal genome or transcriptome. Here, we aimed to assess if these 'contaminations' provide information with regard to biologically important microorganisms associated with the individual. To achieve this, we examined whether the short read data from Apis retrieved elements of its well established microbiome. To this end, we screened almost 1,000 short read libraries of honey bee (Apis sp.) DNA sequencing project for the presence of microbial sequences, and find sequences from known honey bee microbial associates in at least 11% of them. Further to this, we screened ∼500 Apis RNA sequencing libraries for evidence of viral infections, which were found to be present in about half of them. We then used the data to reconstruct draft genomes of three Apis associated bacteria, as well as several viral strains de novo. We conclude that 'contamination' in short read sequencing libraries can provide useful genomic information on microbial taxa known to be associated with the target organisms, and may even lead to the discovery of novel associations. Finally, we demonstrate that RNAseq samples from experiments commonly carry uneven viral loads across libraries. We note variation in viral presence and load may be a confounding feature of differential gene expression analyses, and as such it should be incorporated as a random factor in analyses.


Development and evaluation of Chitosan nanoparticles based dry powder inhalation formulations of Prothionamide.
Prothionamide (PTH), a second line antitubercular drug is used to administer in conventional oral route. However, its unpredictable absorption and frequent administration limit its use. An alternate approach was thought of administering PTH through pulmonary route in a form of nanoparticles, which can sustain the release for several hours in lungs. Chitosan, a bio-degradable polymer was used to coat PTH and further freeze dried to prepare dry powder inhaler (DPI) with aerodynamic particle size of 1.76μm. In vitro release study showed initial burst release followed by sustained release up to 96.91% in 24h. In vitro release further correlated with in vivo study. Prepared DPI maintained the PTH concentration above MIC for more than 12h after single dose administration and increased the PTH residency in the lungs tissue more than 24h. Animal study also revealed the reduction of dose in pulmonary administration, which will improve the management of tuberculosis.


Myosin Va molecular motors manoeuvre liposome cargo through suspended actin filament intersections in vitro.
Intracellular cargo transport relies on myosin Va molecular motor ensembles to travel along the cell's three-dimensional (3D) highway of actin filaments. At actin filament intersections, the intersecting filament is a structural barrier to and an alternate track for directed cargo transport. Here we use 3D super-resolution fluorescence imaging to determine the directional outcome (that is, continues straight, turns or terminates) for an ∼10 motor ensemble transporting a 350 nm lipid-bound cargo that encounters a suspended 3D actin filament intersection in vitro. Motor-cargo complexes that interact with the intersecting filament go straight through the intersection 62% of the time, nearly twice that for turning. To explain this, we develop an in silico model, supported by optical trapping data, suggesting that the motors' diffusive movements on the vesicle surface and the extent of their engagement with the two intersecting actin tracks biases the motor-cargo complex on average to go straight through the intersection.


A case of pyriform sinus fistula infection with double tracts.
Pyriform sinus fistula is a rare clinical entity and the precise origin remains controversial. The fistula is discovered among patients with acute suppurative thyroiditis or deep neck infection of the left side of the neck and is usually located in the left pyriform sinus. To the best of our knowledge, only a single tract has been reported to be responsible for pyriform sinus fistula infection. We present a case of a 13-year-old female patient with a pyriform sinus fistula that caused a deep infection of the left side of the neck and showed double-tract involvement discovered during surgical resection of the entire fistula. Both tracts arose around the pyriform sinus and terminated at the upper portion of the left lobe of the thyroid.


Serum folates during the reproductive cycle of sows.
In a first trial, serum folates concentration was measured in 105 sows randomly distributed into seven groups of 15 animals each. Each group represented one time period of the reproductive cycle: weaning, mating, 15, 30, 60, 90 and 110 d of gestation. The average serum folates concentrations for the different groups of sows were, expressed as ng/ml +/- SE, 99.5 +/- 8.9, 68.5 +/- 9.6, 63.9 +/- 7.4, 59.5 +/- 5.7, 39.6 +/- 5.7, 45.3 +/- 5.8 and 49.1 +/- 6.3, respectively. Results showed a biphasic decrease in serum folates levels, first at mating and then at 60 d of gestation. These results indicate a possible deficiency in serum folates during mid-gestation. In a second trial, 20 sows were assigned randomly to four groups of five animals each, representing four time periods of the reproductive cycle: weaning, mating, 30 and 60 d of gestation. One intramuscular injection of 15 mg folic acid was administered to all sows and serum folates concentration was measured before the injection and at 2-d intervals during a period of 14 d after the injection. An increase in serum folates was noted in sows of all groups. The time response curves observed after the injection are presented and discussed. The decrease in folates levels observed during early and mid-gestation could be moderated by im administration of this vitamin.


Distributed quasi-Bragg beam splitter in crossed atomic waveguides.
We perform an experimental and theoretical study of a novel distributed quasi-Bragg splitter for cold atoms propagating in crossed optical waveguides. The atoms are guided by horizontal red-detuned laser beams which cross with an angle of roughly 90°. The lattice formed by the interference between the two waveguides is used as a quasi-Bragg splitter to continuously deflect the atomic flux from one waveguide into the other. In the limit of strong waveguide confinement and depending on the velocity of the cloud, three main regimes are observed corresponding (1) to the absence of reflection, (2) to partial reflection and (3) to full reflection into the second waveguide. In view of the application to atom interferometry, the condition to split the cloud into mainly two equally-populated fragments is only met in the highest velocity regime, where the fraction of reflected and transmitted atoms can be controlled by tuning the lattice height. A diagnostic of the momentum distribution shows that a quasi-Bragg splitter with the occupation of mainly two momentum states is achieved in this regime. This behaviour can be understood by considering the band structure associated with the potential in the crossing region and agrees with numerical simulations of the atomic dynamics.


An integrated treatment approach: a case report for dentinogenesis imperfecta type II.
Dentinogenesis imperfecta type II or hereditary opalscent dentin is one of the most common autosomal dominant anomaly of dentin that occurs in both sex affecting approximately 1:8000 persons. Clinically this disorder is characterized by variable blue gray to yellow brown teeth, with fracture of enamel and excessive wear. The treatment strategy is focused towards protecting teeth from further wear and tear and total oral rehabilitation of patient with paramount importance to aesthetics, obtaining an appropriate vertical dimension and providing soft tissue support which will help to return the facial profile to a more normal appearance. A multidisciplinary treatment planning is required for treatment of these individuals.


The absorption of insulin.
It is desirable to improve metabolic control in diabetics receiving insulin. Studies on insulin kinetics provide information that may be useful in the optimization of the injection scheme. Absorption has been measured using 125I-insulin as marker and counting the residual activity with a crystal detector. Plasma insulin has been measured (by radioimmunoassay) in the absence of insulin antibodies. The relationship between the rate of absorption and exogenous insulinemia was analyzed using a simple mathematical model. The time course of plasma insulin was calculated for various insulin preparations, including mixtures. The data suggest the significance of the injection site for the effect of insulin, e.g., a more rapid effect after injection into the abdominal subcutaneous tissue. The pattern of exogenous insulinemia in patients treated with insulin bears no resemblance to that in normal subjects. The calculated patterns of exogenous plasma insulin after injection of various preparations suggest that insulin therapy might be improved to obtain a better and more physiological metabolic control.


Carboxylate-directed in vivo assembly of virus-like nanorods and tubes for the display of functional peptides and residues.
Uniform dimensions and genetic tractability make filamentous viruses attractive templates for the display of functional groups used in materials science, sensor applications, and vaccine development. However, active virus replication and recombination often limit the usefulness of these viruses for such applications. To circumvent these limitations, genetic modifications of selected negatively charged intersubunit carboxylate residues within the coat protein of tobacco mosaic virus (TMV) were neutralized so as to stabilize the assembly of rod-shaped virus-like particles (VLPs) within bacterial expression systems. Here we show that TMV-VLP nanorods are easily purified, stable, and can be programmed in a variety of configurations to display functional peptides for antibody and small molecule binding.


Structural design of cubic Sr,V:CeFeO3 thin films with a strong magneto-optical effect and high compatibility with a Si substrate.
This paper focuses on strong magneto-optical thin films that closely match a Si substrate. The orthorhombic perovskite crystal structure of CeFeO3 was optimized to a cubic perovskite structure by introducing strontium and vanadium ions into lattice. The cubic Ce1-xSrxFe1-xVxO3 (x = 0.3, 0.5, 0.7) thin films with high quality and high growth orientation were prepared on a Si substrate by using the RF magnetron sputtering method. Moreover, the birefringence effect, which may weaken the magneto-optical effect, should not occur in the cubic thin film. The calculation results based on density functional theory show that the increased electronic transition probability is attributed to the strong spin-coupling between the hybrid Ce3+ 4f and Fe3+/V4+ 3d states. The magnetic circular dichroism ellipticity |ΨF| of the Ce0.7Sr0.3Fe0.7V0.3O3 thin film is up to 4300 deg. cm-1, which indicates a strong magneto-optical effect. Therefore, the cubic Ce1-xSrxFe1-xVxO3/Si film with high Ce3+ concentration is expected to be a new candidate for integrated magneto-optical devices.


Acrosome biogenesis begins during meiosis: evidence from the synthesis and distribution of an acrosomal glycoprotein, acrogranin, during guinea pig spermatogenesis.
The biogenesis of the sperm-specific organelle, the acrosome, was investigated using an acrosomal glycoprotein as a marker of development. This component, which we have named acrogranin, was purified from an acid extract of guinea pig testes by standard chromatographic procedures. The molecular weight of reduced acrogranin was determined to be 67,000 by analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunization of female rabbits with purified acrogranin produced an antiserum that recognized a single protein with Mr = 67,000 in an acid extract of guinea pig testes. By indirect immunofluorescence, acrogranin was found only in the acrosome of mature sperm. In haploid spermatids, acrogranin was localized in the developing acrosome and, weakly, in the cytoplasm. Acrogranin was also detected in the cytoplasm and juxtanuclear region in putative proacrosomal granules of meiotic cells (pachytene spermatocytes). Detergent extracts from different purified germ cell populations contained only the Mr = 67,000 form of acrogranin, but sperm extracts had four lower Mr immunoreactive forms not present in the testicular extracts. By two-dimensional gel electrophoresis, acrogranin was found to be an acidic glycoprotein. Analysis of glycosylated and trifluoromethanesulfonic acid-deglycosylated acrogranin indicated that the antibody recognized polypeptide determinants. After highly enriched germ cell populations were labeled overnight with [35S]methionine and extracted with detergent, anti-acrogranin immunoprecipitated a single protein of Mr = 67,000. The synthesis of acrogranin by pachytene spermatocytes and round spermatids was similar, but the synthesis of the glycoprotein by condensing spermatids was markedly reduced. These studies demonstrate that acrosome biogenesis, as determined by the synthesis of a specific acrosomal component, begins during meiosis and continues through the early stages of spermiogenesis.


Directly observed treatment short course (DOTS) appears to have reduced the self-care role of the-pulmonary tuberculosis patient: evidence from a correlational study between personal health beliefs (PHB) and self-care practices (SCP).
To examine the relationship between personal health beliefs and self-care practices among 69 PTB patients aged 25 to 65 years at a tuberculosis clinic in Zimbabwe, in order to determine the role patients can play in self-care. Analysis of collected demographic data, personal health beliefs (PH B) and self-care practices (SCP) of PTB patients. Gwanda Provincial Hospital (GPH) Tuberculosis Clinic. PTB patients in the (GPH) register who were taking treatment. Key components of the study included administration of an interview schedule to 69 PTB patients on treatment, and the analysis and comparison of personal health beliefs and self-care practices. Scores of personal health beliefs, self-care practices, perceived self-efficacy, perceived threats, and cost-benefit analysis. Sixty- nine PTB patients with a median age of 38, screened during the month of March, 2009, showed a weak positive Pearson's correlational coefficient of (R2=0.177), indicating that personal health beliefs may have some influence on self-care practices. The regression analysis showed an association of 3.1%, thus health beliefs are responsible for self-care undertaken by 3.1 in a 100 PTB patients. Directly Observed Treatment Short Course (DOTS) seems to have reduced the self-care practice of PTS patients. It seems the PTB patient has a potential role to play in the management of his own treatment.


Anti-cancer activity of C. cainito leaves explained using its compounds docked with p53.
Extensive research on the mutant P53 protein has identified its pivotal role in anti-apoptosis mechanisms, drug resistance, and cancer progression in OSCC. The mass spectrum revealed the pharmacologically significant bioactive compounds reported for the first time in C cainito. Molecular docking investigation has identified four potential new P53 inhibitors compared with the standard P53 inhibitors. Hence, this analysis reinforces the likelihood of anti-cancer activities in C. cainito leaves.


Dynamic renal scintigraphy in children with vesicoureteral reflux and suspected coexisting ureteropelvic junction obstruction.
We evaluated whether findings on voiding cystourethrography suggesting ureteropelvic junction (UPJ) obstruction coexists with vesicoureteral reflux (VUR) are associated with parameters on dynamic renal scintigraphy that support significant obstruction. We reviewed records of 44 patients referred for scintigraphy after voiding cystourethrography performed at age 1 day to 9.4 years (mean 7 months, median 1.7 months) showed VUR and findings suggestive of UPJ obstruction (blockage of contrast material at the UPJ, contrast dilution in the renal pelvis, slow renal pelvic drainage). Results were correlated with Society for Fetal Urology hydronephrosis grade and ureteral morphology. Halftime was in the obstructive range (20 minutes or greater) for 7 of 47 kidneys (15%). The prevalence of a post-furosemide pelvicaliceal drainage halftime in the obstructive range increased with hydronephrosis grade (0% grade 1, 17% grade 2, 50% grade 3 to 4, p = 0.002) but did not vary with ureteral morphology (p = 0.08). In 12 of 38 cases (31%) where suspected UPJ obstruction was unilateral and a contralateral kidney was present differential uptake of the affected kidney was less than 45%. The prevalence of differential uptake less than 45% was higher in patients with than without ureteral dilatation (48% vs 12%, p = 0.02) but did not vary with hydronephrosis grade (p = 0.93). In children with VUR and suspected coexisting UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present but is unlikely to do so if neither is observed.


Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia.
The response of Philadelphia chromosome (Ph(+)) acute lymphoblastic leukemia (ALL) to treatment by BCR-ABL tyrosine kinase inhibitors (TKIs) has been disappointing, often resulting in short remissions typified by rapid outgrowth of drug-resistant clones. Therefore, new treatments are needed to improve outcomes for Ph(+) ALL patients. In a mouse model of Ph(+) B-lineage ALL, MCL-1 expression is dysregulated by the BCR-ABL oncofusion protein, and TKI treatment results in loss of MCL-1 expression prior to the induction of apoptosis, suggesting that MCL-1 may be an essential prosurvival molecule. To test this hypothesis, we developed a mouse model in which conditional allele(s) of Mcl-1 can be deleted either during leukemia transformation or later after the establishment of leukemia. We report that endogenous MCL-1's antiapoptotic activity promotes survival during BCR-ABL transformation and in established BCR-ABL(+) leukemia. This requirement for MCL-1 can be overcome by overexpression of other antiapoptotic molecules. We further demonstrate that strategies to inhibit MCL-1 expression potentiate the proapoptotic action of BCL-2 inhibitors in both mouse and human BCR-ABL(+) leukemia cell lines. Thus, strategies focused on antagonizing MCL-1 function and expression would be predicted to be effective therapeutic strategies.


The COVID-19 third wave in Myanmar following the military coup.
Background: COVID-19 seriously hit Myanmar between June and August 2021, a few months after the military coup, though the first and second waves in 2020 were managed effectively by the government. People in Myanmar experienced serious consequences of the COVID-19 pandemic precipitated by the disorganized health system under the military junta. This study aimed to analyse the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar. Methods: An online survey was conducted using a Google form. People with the symptoms of COVID-19 and those who died from COVID-19 between June and August 2021 were eligible to participate. The Google form was extracted into an Excel datasheet and analysed using Stata v16.1. Results: Among the 29,171 participants, 76.7% were over 30 years old and 56.4% were female. A majority of participants were from highly populated regions: Yangon (17,220; 59%) (Business capital), Mandalay (3,740; 12.8%) and Sagaing (1,546; 5.3%). Participants sought health care from telegram/other online services (34%), home care by health care providers (22%), private clinics (13%) and public hospitals run under the military junta (5%). Overall, 15% of participants died, of which, 72% occurred at home and 17% at public hospitals. Significantly higher proportions of deaths were seen among participants over 60 years than other age groups and males (p<0.001). Death proportions at different weeks from June to August 2021 ranged from 12.4% to 17.3%, much higher than the military junta's reports. Overall, 25% of participants received oxygen therapy. Conclusions: Death proportions in different weeks were consistently over 12%. The majority of participants received tele/online and home treatment services. Most deaths occurred at home. Findings indicated the high COVID-19 case fatality rates with limited access to public hospital care during the third wave. The data from this study suggest that the outcomes were adversely impacted by the military coup.


The value of digital subtraction angiography in peripheral vascular diseases.
The iliac and subclavian arteries and their distal branches were studied by digital subtraction angiography (DSA) in 79 patients and the results compared with conventional angiograms for 35 patients. Techniques, results, advantages and disadvantages are described. DSA (both intravenous and intra-arterial) looks very promising in the diagnosis of peripheral vascular disease.


Effects of Herb-Partitioned Moxibustion on Autophagy and Immune Activity in the Colon Tissue of Rats with Crohn's Disease.
To investigate the mechanism of action of herb-partitioned moxibustion on CD from the perspective of autophagy and immunity. The expression of microtubule-associated protein LC3II and SQSTM1/p62 in the colon tissues was detected by immunohistochemistry. Western blot was used to detect the expression of autophagic and immune-related proteins in the colon, such as LC3II, SQSTM1/p62, Beclin1, ATG16L1, NOD2, IRGM, IL-1β, IL-17, and TNF-β. mRNA levels of immune factors, such as IL-1β, IL-17, and TNF-β, and autophagy signaling molecules, such as PI3KC, AKT1, LKB1, and mTOR, were detected by RT-qPCR. Herb-partitioned moxibustion reduced the protein levels of ATG16L1, NOD2, IRGM, LC3II, and Beclin1 (P < 0.01) and both the protein and mRNA levels of IL-1β, IL-17, and TNF-β in CD rats (P < 0.01 or P < 0.05), and it also increased the expression of SQSTM1/p62 protein (P < 0.01). The modulatory effects of herb-partitioned moxibustion on ATG16L1, NOD2, IRGM, LC3II, TNF-β, and IL-17 protein and IL-1β protein and mRNA were better than those of mesalazine (P < 0.01 or P < 0.05). Herb-partitioned moxibustion also reduced colon PI3KC, AKT1, and LKB1 mRNA expressions in CD rats (P < 0.01 or P < 0.05) and increased mTOR protein expression (P < 0.05). And the modulatory effect of herb-partitioned moxibustion on AKT1 mRNA was better than that of mesalazine (P < 0.05). Herb-partitioned moxibustion may inhibit excessively activated autophagy and modulate the expression of immune-related factors by regulating the LKB1-mTOR-PI3KC signal transduction networks, thereby alleviating intestinal inflammation in CD rats.


Effect of intracoronary tirofiban on platelet alpha-granule membrane protein and myocardial perfusion level during emergency percutaneous coronary intervention.
This study aimed to investigate the effect of intracoronary application of tirofiban on platelet alpha-granule membrane protein (GMP-140) and myocardial perfusion levels during emergency percutaneous coronary intervention (PCI). A total of 70 patients who accepted emergency PCI treatment were randomly divided into tirofiban and control groups. We determined GMP-140 and troponin I (cTnI) levels before and 12 h after surgery, as well as N-terminal pro-brain natriuretic peptide levels 1 and 7 days after surgery in the two groups. The results showed that GMP-140 and cTnI levels were significantly (P < 0.01) lower in the tirofiban group than in the control group 12 h after operation (17.99 ± 1.01 vs 24.56 ± 1.96 μg/L and 50.96 ± 2.20 vs 58.69 ± 2.34 ng/mL, respectively). The D-value of the N-terminal pro-brain natriuretic peptide levels between 1 and 7 days after operation was significantly higher in the tirofiban group than in the control group (894.19 ± 90.91 vs 829.50 ± 84.18 pg/mL; P < 0.01). The intracoronary application of tirofiban during emergency PCI clearly reduced the GMP-140 level, inhibited the activation function of platelets, improved myocardial perfusion, and helped recover cardiac function in patients.


Prevalence of antibodies to Neospora caninum, Sarcocystis neurona, and Toxoplasma gondii in wild horses from central Wyoming.
Sarcocystis neurona, Neospora caninum, N. hughesi, and Toxoplasma gondii are 4 related coccidians considered to be associated with encephalomyelitis in horses. The source of infection for N. hughesi is unknown, whereas opossums, dogs, and cats are the definitive hosts for S. neurona, N. caninum, and T. gondii, respectively. Seroprevalence of these coccidians in 276 wild horses from central Wyoming outside the known range of the opossum (Didelphis virginiana) was determined. Antibodies to T. gondii were found only in 1 of 276 horses tested with the modified agglutination test using 1:25, 1:50, and 1:500 dilutions. Antibodies to N. caninum were found in 86 (31.1%) of the 276 horses tested with the Neospora agglutination test--the titers were 1:25 in 38 horses, 1:50 in 15, 1:100 in 9, 1:200 in 8, 1:400 in 4, 1:800 in 2, 1:1,600 in 2, 1:3,200 in 2, and 1:12,800 in 1. Antibodies to S. neurona were assessed with the serum immunoblot; of 276 horses tested, 18 had antibodies considered specific for S. neurona. Antibodies to S. neurona also were assessed with the S. neurona direct agglutination test (SAT). Thirty-nine of 265 horses tested had SAT antibodies--in titers of 1:50 in 26 horses and 1:100 in 13. The presence of S. neurona antibodies in horses in central Wyoming suggests that either there is cross-reactivity between S. neurona and some other infection or a definitive host other than opossum is the source of infection. In a retrospective study, S. neurona antibodies were not found by immunoblot in the sera of 243 horses from western Canada outside the range of D. virginiana.


A minimally invasive method to evaluate 131I kinetics in blood.
The dose limiting factor for 131I therapy in patients with thyroid cancer is myelotoxicity, thus an accurate determination of radioiodine activity in the red marrow is of paramount importance. The reference method for red marrow dosimetry in radiometabolic therapy is based on the measurement of radioiodine kinetics, particularly the activity/time curve in blood. Such a measurement requires withdrawal of blood samples at various times after 131I administration. This procedure involves some potential risk from the radiation protection point of view, such as possible contamination of personnel with blood and disposal of the radioactive blood samples (and syringes). We present here a minimally invasive method to evaluate radioiodine kinetics in the blood, which only requires one blood sample and a set of measurements on the patient's thigh made with a collimated NaI(Tl) probe. The method has been validated in four patients treated with 131I for thyroid cancer.


The optimal pallidal target in deep brain stimulation for dystonia: a study using a functional atlas based on nonlinear image registration.
Deep brain stimulation (DBS) of the globus pallidus internus is established as efficacious for dystonia, yet the optimal target within this structure is not well defined. Published evidence suggests that spatial normalization provides a better estimate of DBS lead location than traditional methods based on standard stereotactic coordinates. We retrospectively reviewed our pallidal implanted dystonia population. Patient imaging scans were morphed into an MRI atlas using a nonlinear image registration algorithm. Active contact locations were projected onto the atlas and clusters analyzed for the degree of variance in two groups: (1) good and poor responders and (2) cervical (CD) and generalized dystonia (GD). The average active contact location between CD and GD good responders was distinct but not significantly different. The mean active contact for CD poor responders was significantly different from CD responders and GD poor responders in the dorsoventral direction. A normalized imaging space is arguably more accurate in visualizing postoperative leads. Despite some separation between groups, this data suggests there was not an optimal pallidal target for common dystonia patients. Degrees of variance overlapped due to a large degree of individual target variation. Patient selection may ultimately be the key to maximizing patient outcomes.


DNA damage induced by the environmental carcinogen butadiene: identification of a diepoxybutane-adenine adduct and its detection by 32P-postlabelling.
To date only a few studies have been undertaken on DNA adducts formed by epoxybutene (EB) and diepoxybutane (DEB), the two active metabolites of 1,3-butadiene. Our interests have focused on further investigating DNA alkylation by the two epoxides, especially in relation to the development of a method for human biomonitoring. Here, following the reaction of deoxyadenosine monophosphate and poly(dA-dT)(dA-dT) with DEB and subsequent HPLC, we have identified an adenine adduct. MS analyses indicate the structure of an adenine adducted by DEB at the N6 position. A HPLC/32P-postlabelling method was developed for its measurement in DNA samples and the adduct was detected in calf thymus DNA and DNA from Chinese hamster ovary cells exposed to DEB. The 100% labelling efficiency during postlabelling, the amount of the adduct and its elution before the normal nucleotides during HPLC suggest it could be a suitable indicator of BUT exposure.


Fixed Drug Eruption Late in the Course of Capecitabine Therapy.
A fixed drug eruption (FDE) is a toxic skin effect thought to be caused by delayed cell-mediated hypersensitivity to a pharmaceutical agent. We report herein the first known patient with capecitabine-induced FDE that appeared relatively late in the course of adjuvant therapy for rectal cancer. The temporal association with capecitabine use and prompt disappearance after capecitabine discontinuation make this relationship probable. Knowledge about this dermatologic skin effect seen with oral fluoropyrimidines should avoid unnecessary diagnostic workup and provide the necessary patient reassurance.


Understanding the Reactivity of CO3·- and NO2· Radicals toward S-Containing and Aromatic Amino Acids.
The reactivity of CO3·- and NO2· radicals toward six amino acid side chains namely, cysteine (Cys), methionine (Met), phenylalanine (Phe), tyrosine (Tyr), histidine (His), and tryptophan (Trp), has been explored using state-of-art density functional theory (DFT) and transition state theory (TST). Three reaction mechanisms, namely hydrogen atom abstraction (HAT), radical adduct formation (RAF), and single electron transfer (SET), have been considered for detailed study. While CO3·- radical is highly reactive toward majority of amino acids, the reactivity of NO2· radical is limited. The CO3·- radical creates oxidative damage to amino acid residues predominantly via HAT mechanism with moderate to high rate constant. Kinetic data suggest that tryptophan and tyrosine moiety possess the highest reactivity while the phenylalanine furnishes slow reaction. On the other hand, NO2· radical cannot produce direct damage toward most of the amino acids except tryptophan and histidine. The NO2· radical reacts exclusively by SET mechanism with 6.01 × 106 M-1 s-1 and 4.69 × 102 M-1 s-1 rate constant for Trp and His, respectively. Therefore, the CO3·- radical may cause severe damage to amino acid side chains during oxidative stress conditions, whereas the NO2· radical is mostly inert. Moreover, the reaction of CO3·- and NO2· radicals with amino acid radical intermediates generate variety of oxidation and nitro products which explain the formation of different experimentally characterized biomarkers during oxidative stress.


New strategies for massive transfusion in the bleeding trauma patient.
Trauma continues to be the leading cause of death among those younger than 40 years. A major cause of death within the first 24 hours is hemorrhage. Many of these patients present with severe coagulopathy and require massive transfusion. Earlier control of coagulopathy has been shown to improve survival. To address coagulopathy sooner, changes in the way we identify and resuscitate the exsanguinating trauma patient have evolved. These changes include early identification of at-risk patients and early, aggressive transfusion of plasma and platelets. This article reviews the key massive transfusion triggers and resuscitation strategy of damage control resuscitation.


Effect of using a Planecta™ port with a three-way stopcock on the natural frequency of blood pressure transducer kits.
Blood pressure transducer kits are equipped with two types of Planecta™ ports-the flat-type Planecta™ port (FTP) and the Planecta™ port with a three-way stopcock (PTS). We reported that FTP application decreased the natural frequency of the kits. However, Planecta™ is an invaluable tool as it prevents infection, ensures technical simplicity, and excludes air. Hence, an ideal Planecta™ port that does not decrease the frequency characteristics is required. As a first step in this direction, we aimed to assess the influence of PTSs on the natural frequency of blood transducer kits. A DTXplus transducer kit (DT4812J; Argon Medical Devices, TX, USA) was used along with ≥1 PTSs (JMS, Hiroshima, Japan), and the frequency characteristics were assessed. The natural frequency and damping coefficient of each kit were obtained by using frequency characteristics analysis software, and these parameters were evaluated by plotting them on Gardner's chart. Regardless of whether one or two PTSs were inserted, the natural frequency of the kits only slightly decreased (from 42.5 to 41.1 Hz, when 2 PTSs were used). Thus, the frequency characteristics of the kits with PTSs were adequate for pressure monitoring. The insertion of ≥2 FTPs in pressure transducer kits should be avoided, as they markedly decrease the natural frequency and lead to underdamping. However, the effect of PTS insertion in pressure transducer kits on the frequency characteristics is minimal. Thus, we found that the use of PTS markedly improved the frequency characteristics as compared to the use of FTP.


Improved method for the purification of biologically active transcobalamin II.
Transcobalamin II (TC II) was purified about 300,000-fold from Cohn fraction III using a modification of the procedure described by Allen and Majerus (J. Biol. Chem. 247, 7709-7717 (1972)). The simplified method incorporated isoelectric precipitation of the TC II into the purification scheme which permitted the elimination of two column chromatographic steps originally reported by the above workers. The final preparation had 26.7 mug of vitamin B12 (B12) bound per mg of protein and an A280/A361 ratio of 2.05, both of which are in good agreement with the reported values. The purified TC II was biologically active with respect to its ability to facilitate penetration of B12 into HeLa cells in tissue culture.


Long-term outcomes of laparoscopic sleeve gastrectomy as a primary bariatric procedure.
Laparoscopic sleeve gastrectomy (LSG) has been established as a reliable bariatric procedure, but questions have emerged regarding its long-term results. Our aim is to report the long-term outcomes of LSG as a primary bariatric procedure. Retrospective analysis of patients submitted to LSG between 2005 and 2007 in our institution. Long-term outcomes at 5 years were analyzed in terms of body mass index (BMI), excess weight loss (EWL) and co-morbidities resolution. Surgical success was defined as %EWL>50%. Also, we compared long-term results according to preoperative BMI, using Mann-Whitney test. A total of 161 LSG were analyzed, and 114 patients (70.8%) were women. The median age was 36 years old (range 16-65), median preoperative BMI was 34.9 kg/m(2) (interquartile range [IQR], 33.3-37.5). A total of 112 patients (70%) completed 5 years of follow-up. At the fifth year, median BMI and %EWL was 28.5 kg/m(2) (IQR: 25.8-31.9) and 62.9% (IQR: 45.3-89.6), respectively, with a surgical success of 73.2% of followed patients. According to preoperative BMI, surgical success was achieved in 80% of patients with BMI<35 kg/m(2), 75% of BMI 35-40 kg/m(2), and 52.6% of BMI>40 kg/m(2), with significant lower %EWL in patients with BMI>40 kg/m(2) (P = .001 and .004). Dyslipidemia and insulin resistance resolution was 80.7% and 84.7%, respectively. A total of 26.7% of patients reported new-onset gastroesophageal reflux symptoms at 5 years. LSG as a primary procedure is a reliable surgery. We observed positive long-term outcomes of %EWL and co-morbidities resolution. In our series, best results are seen in patients with preoperative BMI<40 kg/m(2).


Abortion, value and the sanctity of life.
In Life's Dominion Dworkin argues that the debate about abortion is habitually misconstrued. Substantial areas of agreement are overlooked, while areas of disagreement are, mistakenly, seen as central. If we uncover a truer picture, then hope of a certain accord may no longer seem vain. I dispute many of these claims. Dworkin argues that both sides in the debate are united in believing that life is sacred, or intrinsically valuable. I disagree. I maintain that only in a very attenuated sense of intrinsic value will this be agreed upon. I consider how an account of such value might be further fleshed out, but suggest, if this is done on any plausible lines, agreement will fall away. Dworkin argues, also, that the issue of personhood, does not, contrary to widespread belief, keep the parties apart. Again I disagree. We need to distinguish the question of whether there is in fact dispute over this issue from that of whether there is, in truth, good reason for dispute. And I argue that, rightly or wrongly, the issue of personhood remains central. Dworkin suggests that the purported proximity between the two sides offers some hope of an eventual reconciliation. At least, they will agree to differ, accepting that in this area freedom of choice is paramount. I am sceptical. Even this measure of reconciliation depends upon conservatives giving up positions which, I argue, they will continue to maintain. There is a further point. Dworkin appears to be, in many ways, cautiously optimistic. I appear, in contrast, to be pessimistic. I argue, however, that only so long as we do disagree over matters of substance is there much hope that our differences might be resolved.


Which Factors Modulate Letter Position Coding in Pre-literate Children?
One of the central landmarks of learning to read is the emergence of orthographic processing (i.e., the encoding of letter identity and letter order): it constitutes the necessary link between the low-level stages of visual processing and the higher-level processing of words. Regarding the processing of letter position, many experiments have shown worse performance in various tasks for the transposed-letter pair judge-JUDGE than for the orthographic control jupte-JUDGE. Importantly, 4-y.o. pre-literate children also show letter transposition effects in a same-different task: TZ-ZT is more error-prone than TZ-PH. Here, we examined whether this effect with pre-literate children is related to the cognitive and linguistic skills required to learn to read. Specifically, we examined the relation of the transposed-letter in a same-different task with the scores of these children in phonological, alphabetic and metalinguistic awareness, linguistic skills, and basic cognitive processes. To that end, we used a standardized battery to assess the abilities related with early reading acquisition. Results showed that the size of the transposed-letter effect in pre-literate children was strongly associated with the sub-test on basic cognitive processes (i.e., memory and perception) but not with the other sub-tests. Importantly, identifying children who may need a pre-literacy intervention is crucial to minimize eventual reading difficulties. We discuss how this marker can be used as a tool to anticipate reading difficulties in beginning readers.


Palladium-catalyzed sequential alkylation-alkenylation reactions. Application to the synthesis of 2-substituted-4-benzoxepines and 2,5-disubstituted-4-benzoxepines.
The synthesis of 2-substituted-4-benzoxepines and 2,5-disubstituted-4-benzoxepines from aryl iodides and bromoenoates is described. This methodology is based on a palladium-catalyzed aromatic substitution followed by an intramolecular Heck sequence. Under the reaction conditions (Pd(OAc)(2) (10 mol %), tri-2-furylphosphine (20 mol %), norbornene (2 equiv), Cs(2)CO(3) (2 equiv), CH(3)CN, 85 degrees C), moderate to excellent yields of benzoxepines bearing numerous substituents (Me, F, Cl, etc.) are obtained.


Secular TRends in DiabEtes in India (STRiDE-I): Change in Prevalence in 10 Years Among Urban and Rural Populations in Tamil Nadu.
The objective of the current study was to assess the secular trends in the prevalence of diabetes, prediabetes, and risk factors from two epidemiological surveys done 10 years apart in three adult populations of different geographic and socioeconomic backgrounds in Tamil Nadu, India. This survey was conducted in 2016 using methodology similar to that used in 2006. Persons aged ≥20 years (n = 9,848) were screened for diabetes, prediabetes, and the risk variables. Fasting and 2-h plasma glucose, lipid profile, blood pressure, anthropometry, and socioeconomic and behavioral details were recorded. Comparative analyses of age-standardized prevalence were done. Prevalence ratios (PRs) between 2016 and 2006 of diabetes and also prediabetes were assessed using Poisson regression analyses. Prevalence of diabetes increased from 18.6% (95% CI 16.6-20.5) to 21.9 (20.5-23.3) in the city, 16.4 (14.1-18.6) to 20.3 (18.9-21.6) in the town, and 9.2 (8.0-10.5) to 13.4 (11.9-14.8) in the periurban villages (PUVs) (P < 0.0001 in all). The PR showed a nonsignificant 8% rise in diabetes in the city, while significant increases had occurred in the town (39%) and PUVs (34%). Prevalence of prediabetes also increased. Age, family history of diabetes, and waist circumference were common risk determinants among the populations. Though general obesity and abdominal obesity increased, the latter was associated with the increased prevalence. Prevalence of diabetes and prediabetes increased in all locations; the rise was significant only in the town and PUVs. Abdominal obesity is significantly associated with increased trend even among the villagers. Rural populations may be targeted for future public health measures to combat diabetes.


In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma cells.
OBJECTIVE To assess the in vitro effects of doxorubicin and tetrathiomolybdate (TM) on cells from a canine hemangiosarcoma cell line. SAMPLE Cultured cells from the canine hemangiosarcoma-derived cell line DEN-HSA. PROCEDURES Cells were treated with TM (0 to 1.5μM), doxorubicin (0 to 5μM), or both with or without 24 hours of pretreatment with ascorbic acid (750μM). Degree of cellular cytotoxicity was measured with a colorimetric assay. Long-term growth inhibition was assessed with a 10-day colony-formation assay. Induction of apoptosis was quantitated by fluorometric assessment of caspase-3 and -7 activation. Formation of reactive oxygen species (ROS) was also detected fluorometrically. RESULTS Exposure of cells to the combination of TM and doxorubicin resulted in a greater decrease in proliferation and clonogenic survival rates than exposure to each drug alone. This treatment combination increased ROS formation and apoptosis to a greater extent than did doxorubicin or TM alone. Ascorbic acid inhibited both TM-induced ROS formation and apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the enhancement in cytotoxic effects observed with DEN-HSA cell exposure to the combination of doxorubicin and TM was achieved through an increase in ROS production. These findings provide a rationale for a clinical trial of this treatment combination in dogs with hemangiosarcoma.


Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis.
Systematic data on the efficacy and safety of COVID-19 vaccine in patients on renal replacement therapy (RRT) remains limited. We conducted a meta-analysis on the efficacy and safety of COVID-19 vaccine in patients on RRT. Eligible studies were identified by systematic literature search in four electronic databases. Twenty-seven studies (4,264 patients) were included for meta-analysis. 99% patients received mRNA vaccine. Patients on RRT showed inferior seropositivity after two-dosed COVID-19 vaccine, 44% lower than the general population. Kidney transplant recipients (KTRs) had significantly lower seropositivity than patients on haemodialysis (HD) or peritoneal dialysis (PD) (26.1 vs. 84.3% and 92.4% respectively, p < 0.001 for both). Compared with healthy controls, KTRs, HD and PD patients were 80% (95% CI: 62-99%), 18% (95% CI: 9-27%) and 11% (95% CI: 1-21%) less likely to develop antibodies after vaccination (p < 0.001, <0.001 and 0.39 respectively). In KTRs, every 1% increase in using mycophenolate was associated with 0.92% reduction in seropositivity (95% CI: -1.68, -0.17, p = 0.021) at population level. The overall adverse event rate attributed to vaccination was 2.1%. Most events were mild. Patients on RRT, particularly KTRs, had significantly reduced antibody response after two-dosed COVID-19 vaccination. Vaccination is generally well tolerated. https://www.crd.york.ac.uk/prospero/, identifier: CRD42021261879.


Selecting treatment for high-risk, localized prostate cancer: the case for radiation therapy.
Prostate cancers that clinically appear to be localized may nonetheless respond poorly to curative treatment. Pretreatment prostate-specific antigen (PSA) level, biopsy Gleason score, and percentage of positive biopsies are all at least as important as clinical stage in predicting treatment outcome. A patient with a nonpalpable tumor, stage T1c disease, serum PSA of 12 ng/mL, and a Gleason score of 8 to 10 in 2 of 12 biopsy cores has a relatively poor prognosis. In a high-risk patient such as this one, the recommended treatment strategy involves a combination of brachytherapy and conformal external beam radiotherapy. In studies comparing treatments in patients stratified according to a variety of risk measures, this combination has shown biochemical disease-free survival rates superior to those seen following radical prostatectomy. The role of androgen suppression remains unclear.


Fetal magnesium homeostasis in the sheep.
The fetal plasma magnesium concentration exceeds that of the mother but the difference is small compared to that of ionized calcium concentration. Although not fully independent of changes in maternal magnesaemia, fetal magnesaemia showed a high degree of autonomy during both hypermagnesaemic and hypomagnesaemic changes induced in the ewe. As with calcium, the placental gradient is reversed after fetal thyroparathyroidectomy (TXPTX) with thyroxine replacement. During perfusion in situ of the placenta from such TXPTX fetuses isolated from the fetus itself, a stable positive placental gradient of magnesium concentration could be re-established between the perfusing blood and the maternal circulation. As with calcium, this gradient could be increased by fetal calf parathyroid extract, parathyroid hormone-related protein (PTHrP 1-141), PTHrP (1-84) but not by PTHrP (1-34). It was concluded that a mid-molecule portion of PTHrP can stimulate a putative placental pump which is responsible for the gradients of both calcium ions and magnesium across the ovine placenta.


The poetics of mourning and faith-based intervention in maladaptive grieving processes in Ethiopia.
The paper is an inquiry into the poetics of mourning and faith-based intervention in maladaptive grieving processes in Ethiopia. The paper discusses the ways that loss is signified and analyzes the meanings of ethnocultural and psychospiritual practices employed to deal with maladaptive grief processes and their psychological and emotional after-effects. Hermeneutics provided the methodological framework and informed the analysis. The thesis of the paper is that the poetics of mourning and faith-based social interventions are interactionally based meaning making processes. The paper indicates the limitations of the study and their implications for further inquiry.


Molecular switches and motors on surfaces.
Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.


Experimental simulation of oxygen profiles and their influence on baker's yeast production: I. One-fermentor system.
In production-scale bioreactors microorganisms are exposed to a continually changing environment. This may cause loss of viability, reduction of the yield of biomass or desired metabolites, and an increase in the formation of by-products. In fed-batch production of baker's yeast, profiles may occur in substrate and oxygen concentrations and in pH. This article deals with the influence of a periodically changing oxygen concentration on the growth of baker's yeast in a continuous culture. Also, influences on the production of ethanol, glycerol, acetic acid, and on the composition of the cells were investigated. It was found that relatively fast fluctuations between oxygen-unlimited and oxygen-limited conditions with a frequency of 1 or 2 min had a distinct influence on the biomass and metabolite production. However, RNA, protein, and carbohydrate contents measured in cells exposed to fluctuations differed little from those in cells from an oxygen-unlimited or an oxygen-limited culture. The respiration and fermentation capacities of cells exposed to fluctuations can be larger than the capacities of cells grown under oxygen-unlimited conditions.