Comparison of gene sets for expression profiling: prediction of metastasis from low-malignant breast cancer.
In the low-risk group of breast cancer patients, a subgroup experiences metastatic recurrence of the disease. The aim of this study was to examine the performance of gene sets, developed mainly from high-risk tumors, in a group of low-malignant tumors. Twenty-six tumors from low-risk patients and 34 low-malignant T2 tumors from patients with slightly higher risk have been examined by genome-wide gene expression analysis. Nine prognostic gene sets were tested in this data set. A 32-gene profile (HUMAC32) that accurately predicts metastasis has previously been developed from this data set. In the present study, six of the eight other gene sets have prognostic power in the low-malignant patient group, whereas two have no prognostic value. Despite a relatively small overlap between gene sets, there is high concordance of classification of samples. This, together with analysis of functional gene groups, indicates that the same pathways may be represented by several of the gene sets. However, the results suggest that low-risk patients may be classified more accurately with gene signatures developed especially for this patient group. Several gene sets, mainly developed in high-risk cancers, predict metastasis from low-malignant cancer.


Concordance between self-reported maltreatment and court records of abuse or neglect among high-risk youths.
We examined the concordance between measures of self-reported maltreatment and court records of abuse or neglect in a sample of detained youths. Data were collected by the Northwestern Juvenile Project and include interviews from 1829 youths aged 10-18 years. Participants were newly detained youths in the Cook County Juvenile Temporary Detention Center in Illinois between 1995 and 1998. Self-reported cases of child maltreatment were compared with court records of abuse or neglect in the Cook County judicial system. We found that among detained youths, 16.6% of those who reported any maltreatment, 22.2% of those who reported the highest level of maltreatment, and 25.1% of those who reported that they required medical treatment as a result of maltreatment had a court record of abuse or neglect. Among those with any self-reported maltreatment, girls (vs boys) and African Americans (vs Whites) were more likely to have a court record (adjusted odds ratio [AOR]=2.18; 95% confidence interval [CI]=1.53, 3.09; and AOR=2.12; 95% CI=1.23, 3.63, respectively). Official records seriously underestimate the prevalence of maltreatment, which indicates that multiple data sources are needed to document the true prevalence of maltreatment.


On the influence of additive and multiplicative noise on holes in dissipative systems.
We investigate the influence of noise on deterministically stable holes in the cubic-quintic complex Ginzburg-Landau equation. Inspired by experimental possibilities, we specifically study two types of noise: additive noise delta-correlated in space and spatially homogeneous multiplicative noise on the formation of π-holes and 2π-holes. Our results include the following main features. For large enough additive noise, we always find a transition to the noisy version of the spatially homogeneous finite amplitude solution, while for sufficiently large multiplicative noise, a collapse occurs to the zero amplitude solution. The latter type of behavior, while unexpected deterministically, can be traced back to a characteristic feature of multiplicative noise; the zero solution acts as the analogue of an absorbing boundary: once trapped at zero, the system cannot escape. For 2π-holes, which exist deterministically over a fairly small range of values of subcriticality, one can induce a transition to a π-hole (for additive noise) or to a noise-sustained pulse (for multiplicative noise). This observation opens the possibility of noise-induced switching back and forth from and to 2π-holes.


Acidic preconditioning inhibits Na+/H+ and Na+/Ca2+ exchanger interaction via PKCepsilon in guinea-pig ventricular myocytes.
An interaction between the Na(+)/Ca(2+) exchanger (NCX) and the Na(+)/H(+) exchanger (NHE) induces reperfusion injury. We investigated the effect of brief repetitive acidosis as acidic preconditioning on NCX and NHE interaction during recovery from acidosis. NCX current with the reversal potential was measured in guinea-pig ventricular myocytes using the whole-cell voltage clamp. The cells were exposed to 5 min of acidosis preceded by two episodes of brief acidosis as acidic preconditioning. Acidosis inhibited NCX current and upon recovery shifted its reversal potential in the negative direction. The shift was prevented by cariporide, but was augmented by a high concentration of phorbol 13-myristate acetate (PMA). Acidic preconditioning prevented the shift, but not in the presence of a selective PKCepsilon inhibitor. A low concentration of PMA, which activates PKCepsilon selectively, prevented the shift, but together with PKCepsilon inhibitor (epsilonV1-2) restored the shift during recovery. 5-Hydroxydecanoate inhibited the effects of acidic preconditioning and those of both low and high concentrations of PMA. The negative shift of NCX reversal potential during recovery from acidosis may be due to [Na(+)](i) accumulation by the NHE. Acidic preconditioning prevented the shift most likely by activating PKCepsilon, which in turn inhibited the NHE. The NHE-NCX interaction may be one of the important end-effectors of preconditioning.


A Novel Unidirectional Porous β-tricalcium Phosphate Bone Substitute in Orthopedic Surgery: A Technical Note and Case Illustrations.
Bone grafting is frequently performed in orthopedic surgeries. Artificial bone is a common grafting material. We have developed an absorbable material for bone regeneration with a unique structure: unidirectional porous β-tricalcium phosphate (AffinosⓇ; Kuraray Co., Ltd., Tokyo, Japan). The most distinctive feature of this material is the ease with which blood can rapidly reach its depths by capillary action due to the unidirectional porous structure. It is also characterized by the presence of micropores, which are known to be beneficial for osteoconductivity both on the surface and inside the material. Favorable artificial bone absorption and regeneration with natural bone were observed in cases of clinical bone graft applications in the spine, extremities, benign bone tumor, trauma, and donor sites. Affinos is useful as a novel absorbable material for bone regeneration in various orthopedic surgeries.


Awake craniotomy: A qualitative review and future challenges.
Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need effective communication skills and knowledge of selecting the right anesthetic drugs to ensure adequate analgesia, akinesia, along with patient satisfaction with the anesthetic conduct throughout the procedure. The challenge of providing adequate anesthetic care to an awake patient for intracranial surgery requires more than routine vigilance about anesthetic management.


What makes cast shadows hard to see?
Visual search is slowed for cast shadows lit from above, as compared to the same search items inverted and so not interpreted as shadows (R. A. Rensink & P. Cavanagh, 2004). The underlying mechanisms for such impaired shadow processing are still not understood. Here we investigated the processing levels at which this shadow-related slowing might operate, by examining its interaction with a range of different phenomena including eye movements, perceptual learning, and stimulus presentation context. The data demonstrated that the shadow mechanism affects the number of saccades during the search rather than the duration until first saccade onset and can be overridden by prolonged training, which then transfers from one type of shadow stimulus to another. Shadow-related slowing did not differ for peripheral and central search items but was reduced when participants searched unilateral displays as compared to bilateral ones. Together our findings suggest that difficulties with perceiving shadows are due to visual processes linked to object recognition, rather than to shadow-specific identification and suppression mechanisms in low-level sensory visual areas. Findings are discussed in the context of the need for the visual system to distinguish between illumination and material.


Radiological assessment of elongated styloid process and ossified stylohyoid ligament.
In this study a radiological assessment of elongated styloid processes and ossified stylohyoid ligaments was performed on 900 panoramic radiographs of 900 patients. The styloid process(s) were found to be longer than 30 mm in 12 cases; in 8 of these cases elongation was bilateral, and in 4 cases it was unilateral, making a total of 20 elongated processes out of a possible 1800--an incidence of 1.1%. The mean length of the elongated processes was 48.15 mm. Symptoms were present in one case of bilateral elongation.


Structure and gelation properties of casein micelles doped with curcumin under acidic conditions.
In this study, the ability of micellar casein (MC) to interact with curcumin during acidification and to produce acid gel was investigated. Steady-state fluorescence spectroscopy of curcumin variation and fluorescence quenching of caseins upon binding with curcumin molecules were evidenced. Increasing the temperature from 20 to 35 °C enhanced MC-curcumin interactions as reflected by the increase in the binding constant from 0.6 ± 0.3 × 10(4) to 6.6 ± 0.6 × 10(4) M(-1). From changes in entropy, enthalpy and Gibbs free energy, hydrophobic interactions were proposed as major binding forces. Static fluorescence MC quenching was demonstrated for the MC-curcumin complex during acidification. From pH 7.4 to pH 5.0, the binding site numbers varied in the range from 1.25 ± 0.05 to 1.49 ± 0.05 and the binding constant kb varied from 3.9 ± 0.4 × 10(4) to 7.5 ± 0.7 × 10(4) M(-1). Small angle X-ray scattering profiles demonstrated that the MC internal structure was unchanged upon curcumin binding. The ζ-potential value of curcumin-doped MC indicated that curcumin did not modify the global charge of MC particles. Acid gelation studied by oscillation rheology and static multiple light scattering at 20 and 35 °C led to a similar behavior for native and curcumin-doped MC suspensions. For the first time, it was demonstrated that the colloidal and functional properties of MC were unchanged when doped with curcumin during acidification.


Polyadenylated RNA of Volvox: isolation and partial characterization.
Polyadenylated RNA from Volvox carteri has been isolated and partially characterized. Electrophoretic profiles of total cellular poly(A)-associated RNA of Volvox spheroids indicate a hetero-disperse distribution of size classes with the range extending from an apparent sedimentation value of approximately 10S to greater than 38S. The radioactive labelling kinetics of this material are typical for rapidly-turning-over RNA. The profiles of poly(A) RNA from different cell types show marked differences in average migration rate. Terminally-differentiated somatic cells contain a greater proportion of material of higher molecular weight than either gonidia (germ cells) or cleaving embryos. The poly(A) segments associated with cellular RNA, obtained by selective RNase digestion are heterogeneous in size as determined by gel electrophoresis with the largest tracts estimated to be 75-80 nucleotides long. Gonidia and embryos display the greatest degree of size heterogeneity, while somatic cells show predominantly the largest classes of poly(A) tract. It is apparent that gross changes in poly(A) RNA metabolism accompany development and cellular differentiation in Volvox.


Expression of core clock genes in colorectal tumour cells compared with normal mucosa: a systematic review of clinical trials.
Experimental studies have shown that some circadian core clock genes may act as tumour suppressors and have an important role in the response to oncological treatment. This study investigated the evidence regarding modified expression of core clock genes in colorectal cancer and its correlation to clinicopathological features and survival. A systematic review was conducted without meta-analysis according to the PRISMA guidelines on 24 March 2014 using PubMed and EMBASE. Eligibility criteria were: study design, original research article, English language, human subjects and gene expression of colorectal cancer cells compared with healthy mucosa cells from specimens analysed by real-time or quantitative real-time polymer chain reaction. The expression of the core clock genes Period, Cryptochrome, Bmal1 and Clock in colorectal tumours were compared with healthy mucosa and correlated with clinicopathological features and survival. Seventy-four articles were identified and 11 studies were included. Overall, gene expression of Period was significantly decreased in colorectal cancer cells compared with healthy mucosa cells. This tendency was also seen in the gene expression of Clock. Other core clock genes did not appear to be differentially expressed. Decreased Period gene expression was correlated to some clinicopathological features. The Period genes seemed to be modified in colorectal tumour cells compared with normal mucosa. Core clock genes might be possible future biomarkers in colorectal cancer.


Prevalence of Hymenolepis nana and H. diminuta from Brown Rats (Rattus norvegicus) in Heilongjiang Province, China.
Hymenolepis nana and Hymenolepis diminuta are globally widespread zoonotic cestodes. Rodents are the main reservoir host of these cestodes. Brown rats (Rattus norvegicus) are the best known and most common rats, and usually live wherever humans live, especially in less than desirable hygiene conditions. Due to the little information of the 2 hymenolepidid species in brown rats in China, the aim of this study was to understand the prevalence and genetic characterization of H. nana and H. diminuta in brown rats in Heilongjiang Province, China. Total 114 fecal samples were collected from brown rats in Heilongjiang Province. All the samples were subjected to morphological examinations by microscopy and genetic analysis by PCR amplification of the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene and the internal transcribed spacer 2 (ITS2) region of the nuclear ribosomal RNA gene. In total, 6.1% (7/114) and 14.9% (17/114) of samples were positive for H. nana and H. diminuta, respectively. Among them, 7 and 3 H. nana isolates were successfully amplified and sequenced at the COX1 and ITS2 loci, respectively. No nucleotide variations were found among H. nana isolates at either of the 2 loci. Seventeen H. diminuta isolates produced 2 different COX1 sequences while 7 ITS2 sequences obtained were identical to each other. The present results of H. nana and H. diminuta infections in brown rats implied the risk of zoonotic transmission of hymenolepiasis in China. These molecular data will be helpful to deeply study intra-specific variations within Hymenolepis cestodes in the future.


Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.
Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.


Lymphoproliferative and serological responses to herpes simplex virus during primary infection, recrudescence, and re-infection in a murine model.
Mice were infected epidermally with herpes simplex virus type 1 (HSV-1) after mild tape stripping. Some were re-infected by the same route several weeks later; recrudescences were induced in others by UV-irradiation before the primary infection followed by re-irradiation and tape stripping at a later date. Clinical symptoms were noted; serological responses to HSV and lymphoproliferative and phenotypic analysis of local lymph node cells were measured throughout. Experience of a primary lesion did not prevent lesions developing again on re-infection although morbidity and mortality were decreased. Recrudescent lesions were less severe than primary or secondary lesions, never zosteriform and healed rapidly. Antibodies to HSV were not found to play a major role in preventing development of lesions. The lymphoproliferative response on primary infection was maximal just after the lesions were most severe and then waned. There was a second, although not accelerated, lymphoproliferative response on re-infection with a persisting high level for at least one month. On recrudescence, limiting dilution culture analysis of lymphoproliferation demonstrated a recruitment within two days of HSV-1 specific lymphocytes to lymph nodes draining sites of lesions, which may limit their severity and duration.


The role of Rho kinase (Rock) in re-epithelialization of adult zebrafish skin wounds.
Complete re-epithelialization of full-thickness skin wounds in adult mammals takes days to complete and relies on numerous signaling cues and multiple overlapping cellular processes that take place both within the epidermis itself and in other participating tissues. We have previously shown that re-epithelialization of full-thickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing allowing for the dissection of specific processes that occur in, or have a direct effect on, re-epithelializing keratinocytes. Recently, we have shown that, in addition to lamellipodial crawling at the leading edge, re-epithelialization of zebrafish partial- and full-thickness wounds requires long-range epithelial rearrangements including radial intercalations, flattening and directed elongation and that each of these processes involves Rho kinase (Rock) signaling. Our studies demonstrate how these coordinated signaling events allow for the rapid collective cell migration observed in adult zebrafish wound healing. Here we discuss the particular contribution of Rock to each of these processes.


Mediational Effects on Motivation to Quit Smoking After Exposure to a Cigarette Pictorial Warning Label Among Young Adults.
Young adults are vulnerable to cigarette package marketing. Pictorial warning labels are recommended for tobacco control. Research should address questions raised in legal challenges including causal mechanisms. Evidence is mixed and understudied among young adults (e.g., discrete emotions and risk perceptions). This study investigated mediators of pictorial warning label effects on motivation to quit smoking among young adult smokers. This study analyzed data from a randomized trial with a 4 week exposure to a cigarette pictorial warning among young adult smokers (N = 229) aged 18-30 with assessments at baseline, immediately post-intervention, and 3 months. Mediation analyses used latent change scores to test the effects post-intervention on fear, anger, and risk perceptions. We also examined whether post-intervention measures predicted change in motivation to quit smoking at 3 months. The first model assessed aggregate risk perceptions and the second model assessed discrete risk perceptions (deliberative, affective). Pictorial warning label exposure led to increases in fear which led to increased motivation to quit smoking for the first (B = 0.12, 95% CI = 0.04, 0.26) and second (B = 0.12, 95% CI = 0.03, 0.25) model. Exposure modestly increased motivation to quit by way of fear and affective risk perceptions (B = 0.01, 95% CI = 0.00, 0.04). Exposure had a direct relationship on increased motivation to quit as well. Findings demonstrate factors contributing to change in motivation to quit smoking among young adult smokers after pictorial warning label exposure. Affective processes are mediators of pictorial warning label effects.


Evaluation of a novel technique in airway clearance therapy - Specific Cough Technique (SCT) in cystic fibrosis: A pilot study of a series of N-of-1 randomised controlled trials.
The aim of this pilot study was to evaluate the efficacy, safety and participants' perception of a novel technique in airway clearance therapy - specific cough technique in cystic fibrosis. We conducted randomised controlled individual trials (N-of-1 randomised controlled trials) in six adults. Each trial included 8 weeks of treatment with two interventions each week, one with specific cough technique and one with forced expiration technique. The efficacy was investigated by a blinded assessor measuring wet weight of sputum (g) after each session. Perceived usefulness and preference was self-reported at the end of study. Additional measurements included oxygen saturation and heart rate before and after each session and lung function (week 2). Three of six participants produced significantly higher mean sputum weight when using specific cough technique, differences being 21%, 38% and 23%, respectively. In three of the six participants, mean sputum weight was lower after forced expiration technique than after specific cough technique in each of the eight treatment pairs. Participant-reported outcomes were completed in all participants. Specific cough technique was reported to be easier to use in daily treatments and more normalising in everyday life. Specific cough technique was well tolerated and accepted by the participants with cystic fibrosis. Specific cough technique was non-inferior to forced expiration technique in terms of sputum production, thus specific cough technique appears to represent a promising alternative for clearing sputum in airway clearance therapy.


Successful delivery of subretinal aflibercept (new surgical technique) for the treatment of submacular hemorrhage in idiopathic polypoidal choroidal vasculopathy.
Submacular hemorrhage (SMH) is often a result of trauma, wet age-related macular degeneration or IPCV and frequently leads to blindness secondary to extreme toxicity of hemoglobin products on photoreceptors. We describe a new technique of subretinal aflibercept injection during pars plana vitrectomy for the treatment of SMH in idiopathic polypoidal choroidal vasculopathy (IPCV). A 55-old male presented with sudden loss of vision (HM) secondary to massive subretinal hemorrhage associated with IPCV. Subretinal injection of aflibercept with a 25 g/42 g cannula coupled to the viscous fluid control unit of a standard vitrectomy system was performed during parsplana vitrectomy. Controlled injection of aflibercept intra-operatively has resulted in a resolution of SMH (confirmed with OCT and ICG). Visual acuity improved from HM to 20/20. This combined approach delivered anti-VEGF agent to target tissue in controlled fashion with the assistance of VFC system (similar to gene therapy) and restored full vision with resolution of SMH.


Measurement and prediction of the rates of spontaneous transfer of phospholipids between plasma lipoproteins.
The purpose of this report is to develop a correlation between the hydrophobicity of a phospholipid as measured by reversed-phase high-performance liquid chromatography and its rate of spontaneous transfer and to use this correlation to predict the rate of transfer of any homologous lipid from any lipoprotein. We have studied the mechanism of transfer of a series of fluorescent or radiolabeled phospholipids among natural and reassembled serum lipoproteins. Fluorescent phosphatidylcholines included those with 9-(1-pyrenyl)nonanoic acid in the sn-2 position and lauric, myristic, palmitic, stearic, oleic or linoleic acid at sn-1. The radioactive phosphatidylcholines contained [3H]oleic acid in the sn-2 position and lauric, myristic, or palmitic acid at sn-1. The kinetics of transfer of the pyrene-labeled lipid were followed by changes in the excimer fluorescence, and that of the radioactive lipids by separation of the donor (lipid-apolipoprotein recombinant) from the acceptor (single bilayer vesicles) on a column of Sephacryl S-200. The retention time of each lipid was measured by high-performance hydrophobic chromatography through a Waters radially compressed C18 column eluted with 75% isopropanol and 25% triethylammonium phosphate (0.15 M). A linear relationship was observed between the rate-constant of transfer and the retention time which suggest that the rate of desorption of phosphatidylcholines from lipoproteins and vesicles is controlled predominately by the hydrophobic effect. For a homologous series of lipids, the rate of transfer can be predicted from retention times obtained from hydrophobic chromatography. The kinetics of transfer of 1-lauroyl-2-[9-(1-pyrenyl)nonanoyl] phosphatidylcholine between isolated human serum lipoproteins exhibits a linear correlation between the transfer half-time and the size of the donor lipoproteins. As a consequence, transfer from very-low-density lipoprotein is 10-times slower than that observed from high-density lipoproteins. The observed correlations between phospholipid transfer rates and both the Stokes radius of the donor and the retention time of the phospholipid on a hydrophobic column permit one to calculate the rate of transfer of homologous molecules between lipid-protein complexes. The results predict that the spontaneous transfer of phospholipids between plasma lipoproteins would be too slow to be a physiologically important phenomena.


Photolabile precursors of inositol phosphates. Preparation and properties of 1-(2-nitrophenyl)ethyl esters of myo-inositol 1,4,5-trisphosphate.
1-(2-Nitrophenyl)ethyl esters of D-myo-inositol 1,4,5-trisphosphate (InsP3) have been synthesized and shown to have suitable properties for use as photolabile precursors of InsP3. Synthesis was accomplished by treatment of InsP3 with 1-(2-nitrophenyl)diazoethane in a CHCl3/water mixture. This resulted in esterification of each of the three phosphate residues in InsP3, the 1-phosphate being more reactive than the 4- or 5-phosphate. Singly esterified P-1, P-4, and P-5 esters, termed P-1, P-4, and P-5 caged InsP3, were isolated from the reaction mixture by anion-exchange HPLC and characterized by 500-MHz 1H NMR spectroscopy. Each of these caged InsP3 esters exists as a pair of diastereoisomers and was identified by examining the effects of pH and nitrophenyl ring current shielding on the chemical shifts of nonexchangeable inositol protons. 1H NMR spectra of InsP3 were analyzed for comparison. On photolysis the compounds released InsP3 with rate constants of 175 (P-1), 225 (P-4), and 280 s-1 (P-5) as determined by monitoring the aci-nitro decay reaction at pH 7.1, 0.2 M ionic strength, 21 degrees C. Quantum yields determined by steady-state near-UV photolysis were 0.65 +/- 0.08 for each compound. P-4 and P-5 caged InsP3 were the most promising biologically inactive InsP3 precursors since at concentrations up to 50 microM they did not release Ca2+ from smooth muscle sarcoplasmic reticulum (SR) and were not metabolized by vascular smooth muscle InsP3 5-phosphatase or bovine brain InsP3 3-kinase.(ABSTRACT TRUNCATED AT 250 WORDS)


Orbital Myositis: A Comprehensive Review and Reclassification.
Orbital myositis occurs in typical and atypical forms. This review summarizes and updates the current state of knowledge of all forms of inflammation affecting extraocular muscle, excluding thyroid-associated orbitopathy. A comprehensive literature review of orbital myositis was performed. Orbital myositis typically occurs in an idiopathic acute form, with painful diplopia due to inflammation in 1 or more extraocular muscles of young adult females, which usually responds to a course of oral corticosteroids. Atypical forms include idiopathic chronic or recurrent orbital myositis, and myositis related to systemic autoimmune, inflammatory, and infective conditions. The commonest associated autoimmune condition is inflammatory bowel disease. Immunoglobulin G4-related ophthalmic disease often affects extraocular muscle. Drug reactions and rarely paraneoplastic disease may also cause extraocular muscle inflammation. Orbital myositis occurs in a typical acute steroid responsive form, but atypical forms related to specific autoimmune and inflammatory conditions are increasingly recognized. Orbital myositis has many similarities to uveitis and would benefit from a systematic approach to nomenclature, diagnosis, and treatment.


Preparation and shape-control of Bi2S3 nanocrystals.
Stable Bi2S3 colloidal nanocrystals with sphere or rod shape were synthesized through a "hot injection" method using organic molecules and macromolecules as ligands. The morphology of Bi2S3 nanocrystals is highly dependent on the experimental parameters, including the reaction temperature, reaction time, reactant ratio and ligands. Especially, adjusting the properties of ligands can lead to an obvious shape evolution of Bi2S3 nanocrystals. When polyvinylpyrrolidone is added as ligands before the reaction, a stable nanodot colloid is formed. While using polyvinylpyrrolidone and thioglycolic acid as mixed ligands benefits for the formation of Bi2S3 nanorods. The synthesized Bi2S3 nanorods were used as seeds in the second-step growing process to achieve a stable, shape and size controlled Bi2S3 nanocrystals. The Bi2S3 nanocrystals were characterized by XRD, UV-Vis and TEM.


Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain.
Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the auditory midbrain increases neural discrimination of complex vocalizations.


Expression of macrophage-selective markers in human and rodent adipocytes.
CD14, CD68 and/or mouse F4/80 or human epidermal growth factor module-containing mucin-like receptor 1 (EMR1) are widely used as macrophage-specific markers. Since macrophages infiltrate several tissues during inflammatory processes, CD14, CD68 and EMR1-F4/80 have been employed to discriminate between tissue-containing macrophages, like adipose tissue (AT), and other cells. Using real-time PCR experiments, we show that isolated adipocytes from humans and mice AT express high levels of CD14 and CD68 mRNA, whereas EMR1-F4/80 is mainly present in the macrophage-containing stroma-vascular fraction. Furthermore, fibroblasts-like cells (adipoblasts), preadipocytes and adipocytes from the murine cell lines, 3T3-F442A and BFC-1, express CD14 and CD68 mRNA and protein as determined by fluorescence-activated cell sorter, but not F4/80 which, as expected, is strongly expressed in the macrophage cell line RAW264.7. These results reinforce the view that EMR1-F4/80 is the best macrophage marker to date and show that CD14 and CD68 are not macrophage-specific proteins.


Shorter sleep duration is associated with social impairment and comorbidities in ASD.
Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. To better understand the connection between sleep duration and ASD severity, we analyzed ASD-related symptoms using the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), IQ scores, and parent reports of the average amount of time slept per night that were available in the medical histories of 2,714 children with ASD in the Simons Simplex Collection (SSC). The mean (SD) sleep duration was 555 minutes. Sleep duration and severity of core ASD symptoms were negatively correlated, and sleep duration and IQ scores were positively correlated. Regression results indicated that more severe social impairment, primarily a failure to develop peer relationships, is the core symptom most strongly associated with short sleep duration. Furthermore, increased severity for numerous maladaptive behaviors assessed on the Child Behavior Checklist, as well as reports of attention deficit disorder, depressive disorder, and obsessive compulsive disorder were associated with short sleep duration. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep ≤420 minutes per night (lower 5th percentile) compared to children sleeping ≥660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1221-1238. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Stable, genetically engineered F(ab')(2) fragments of chimeric TNT-3 expressed in mammalian cells.
F(ab')(2) fragments are desirable structural derivatives of monoclonal antibodies (MAbs) because of their pharmacokinetic properties and bivalent binding to antigen. Production of these fragments, however, has proven difficult because of the variable sensitivity of intact antibodies to proteolytic enzymes, which can result in very low yields and unstable product. To circumvent these problems, we attempted to apply genetic engineering methods to generate stable F(ab')(2) fragments in NSO murine myeloma cells using the glutamine synthase expression system. For these studies, the chimeric MAb, chTNT-3, directed against necrotic regions of solid tumors, was used to generate several F(ab')(2) variants, which contained between one and three cysteine residues at the end of the hinge region. In addition, two different affinity tags (his tag, streptactin tag) were used with each variant to determine the best tag for purification procedures. Stability was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by antigen binding studies and the constructs were tested in vivo to measure their pharmacokinetic properties and biodistribution in normal organs and tumor. The results of these studies show that 3 cysteine residues are required to produce stable F(ab')(2) fragments and that either purification tag can be used with this variant to produce suitable reagents for in vivo studies. Those constructs containing one or two cysteines were found to be unstable and broke down to Fab fragments regardless of the purification tag used. These studies demonstrate that stable, clinically useful F(ab')(2) fragments of chTNT-3 can be produced in mammalian cells by genetic engineering methods.


Zoonotic pathogens from feral swine that pose a significant threat to public health.
The natural fecundity of suids, great ability to adapt to new habitats and desire for local hunting opportunities leading to translocation of feral pigs to regions where they are not yet established have all been instrumental in the home range expansion of feral swine. Feral swine populations in the United States continue to expand, wreaking havoc on agricultural lands, further compromising threatened and endangered species, and posing a microbiological threat to humans, domestic livestock and companion animals. This manuscript thoroughly reviews zoonotic diseases of concern including brucellosis, bovine tuberculosis, leptospirosis, enteric pathogens, both Salmonella spp. and shiga toxin-producing Escherichia coli, and hepatitis E. These pathogens are not a comprehensive list of microbes that are capable of infecting both humans and feral swine, but rather have been selected as they are known to infect US feral swine, direct transmission between wild suids and humans has previously been documented, or they have been shown to be readily transmitted during processing or consumption of feral swine pork. Humans that interact directly or indirectly with feral swine are at much higher risk for the development of a number of zoonotic pathogens. Numerous case reports document transmission events from feral swine and wild boar to humans, and the resulting diseases may be mild and self-limiting, chronic or fatal. Individuals that interact with feral swine should take preventative measures to minimize the risk of disease transmission and all meat should be thoroughly cooked. Additionally, public health campaigns to increase knowledge of the risks associated with feral swine are imperative.


Synthesis-Controlled Polymorphism and Anion Solubility in the Sodium-Ion Conductor Na3InCl6-xBrx (0 ≤ x ≤ 2).
Motivated by the significant transport property improvement of the anion-substituted lithium metal halides, a series of anion mixed solid solutions of Na3InCl6-xBrx (0 ≤ x ≤ 2) are successfully synthesized by ball milling and subsequent annealing. By milling, the Na3InCl6-xBrx solid solution series crystallizes in a monoclinic P21/n phase, while the subsequently annealed Na3InCl6-xBrx series transforms into a trigonal P3̅1c phase. Through annealing and changes of the structure type, greater anion solubility can be achieved. The halide substitution slightly improves the ionic conductivity in the Na3InCl6-xBrx series, indicating that mixed halide compositions and their structural changes affect the ionic transport albeit less strongly than in the lithium analogues such as Li3YCl6-xBrx and Li3InCl6-xBrx.


Alcohol use among physicians in a medical school in Nepal.
The objective of the study was to know about the use of alcohol among physicians and factors that were related to it. This was a cross sectional study conducted among the physicians in a medical school of eastern Nepal. A semi structured questionnaire was used to collect information. There were 55 subjects in the study. Half of them were between 35-45 years age group and one fourth among them were female. There were more than 88% physicians consuming alcohol for more than 10 years. One third used to preferred whisky as their favorites drink. Use of alcohol among them was due to peer pressure and to become a social human being. Most of them drink alcohol occasionally with an average amount 30-60 ml in a sitting and usually in the evening. Most of the time, they use alcohol either in parties or at home. Alcohol use in Nepal is very much prevalent. The use of alcohol is socially accepted in many communities. Uses of alcohol by physicians have direct effect on their health as well as the health of many people because they are role model for many people. They are also in direct contact with the patients. Steps to council the physicians may reduce the consumption of alcohol.


Prostaglandin biosynthesis and catabolism in the developing fetal sheep brain.
The biosynthesis of prostaglandins E2 and F2alpha as well as the catabolism of [9beta- 3H1]prostaglandin F2alpha by homogenates of whole brain from fetal and neonatal lambs was investigated. The biosynthetic measurements utilized the mass spectrometric deuterium isotope dilution-dual ion monitoring technique (Samulsson, B., Hamberg, M., and Sweeley, C.C. (1970) Anal. Biochem. 38, 301-304; Wolfe, L.S., and Pace-Asciak, C. (1972) in Prostaglandins in Fertility Control (Bergström, S., Green, K., and Samuelsson, B., eds) Vol. 2. pp. 201-207, WHO, Karolinska Institutet, Stockholm), whereas the activity of the catabolizing system was measured by the radiolabel dilution-thin layer chromatographic technique reported previously (Pace-Asciak, C. (1975) J. Biol. Chem. 250, 2795-2800). The structures of all products were confirmed by mass spectrometry. Early fetal brain (gestational age 30 to 32 days) contained the highest activity of NAD-dependent prostaglandin 15-hydroxy dehydrogenase which varied inversely with age of the fetus, dropping to almost undetectable levels by neonatal Day 4. Both prostaglandins E2 and F2alpha, were formed by brain from all ages tested and the total prostaglandins formed rose gradually with age. Thus, the period of maximal prostaglandin catabolism which we term the "critical prostaglandin period" appears in the fetal lamb brain around 30 days gestational age or earlier. These findins together with others previously reported by us in other tissues, support the concept that prostaglandin catabolism might play an important role in protecting the developing organ from possible adverse effects of locally formed or circulating prostaglandins. These adverse effects on the developing brain might relate to the known vasoconstrictor properties of the prostaglandins, as well as to their known effects on the induction of cell differentiation.


Study Protocol on Ecological Momentary Assessment of Health-Related Quality of Life Using a Smartphone Application.
Health-Related Quality of Life (HRQoL) is a construct of increasing importance in modern healthcare, and has typically been assessed using retrospective instruments. While such measures have been shown to have predictive utility for clinical outcomes, several cognitive biases associated with human recall and current mood state may undermine their validity and reliability. Retrospective tools can be further criticized for their lack of ecology, as individuals are usually assessed in less natural settings such as hospitals and health centers, and may be obliged to spend time and money traveling to receive assessment. Ecological momentary assessment (EMA) is an alternative, as mobile assessment using mobile health (mHealth) technology has the potential to minimize biases and overcome many of these limitations. Employing an EMA methodology, we will use a smartphone application to collect data on real-time HRQoL, with an adapted version of the widely used WHOQOL-BREF questionnaire. We aim to recruit a total of 450 healthy participants. Participants will be prompted by the application to report their real-time HRQoL over 2 weeks together with information on mood and current activities. At the end of 2 weeks, they will complete a retrospective assessment of their HRQoL and they will provide information about their sleep quality and perceived stress. The psychometric properties of real-time HRQoL will be assessed, including analysis of the factorial structure, reliability and validity of the measure, and compared with retrospective HRQoL responses for the same 2-week testing period. Further, we aim to identify factors associated with real-time HRQoL (e.g., mood, activities), the feasibility of the application, and within- and between-person variability in real-time HRQoL. We expect real-time HRQoL to have adequate validity and reliability, and positive responses on the feasibility of using a smartphone application for routine HRQoL assessment. The direct comparison of real-time and retrospective measures in this study will provide important novel insight into the efficacy of mHealth applications for HRQoL assessment. If shown to be valid, reliable and feasible for the collection of HRQoL data, mHealth applications may have future potential for facilitating clinical assessment, patient-physician communication, and monitoring individual HRQoL over course of treatment.


Convergence of miR-143 overexpression, oxidative stress and cell death in HCT116 human colon cancer cells.
MicroRNAs (miRNAs) regulate a wide variety of biological processes, including tumourigenesis. Altered miRNA expression is associated with deregulation of signalling pathways, which in turn cause abnormal cell growth and de-differentiation, contributing to cancer. miR-143 and miR-145 are anti-tumourigenic and influence the sensitivity of tumour cells to chemotherapy and targeted therapy. Comparative proteomic analysis was performed in HCT116 human colon cancer cells stably transduced with miR-143 or miR-145. Immunoblotting analysis validated the proteomic data in stable and transient miRNA overexpression conditions in human colon cancer cells. We show that approximately 100 proteins are differentially expressed in HCT116 human colon cancer cells stably transduced with miR-143 or miR-145 compared to Empty control cells. Further, Gene Ontology and pathway enrichment analysis indicated that proteins involved in specific cell signalling pathways such as cell death, response to oxidative stress, and protein folding might be modulated by these miRNAs. In particular, antioxidant enzyme superoxide dismutase 1 (SOD1) was downregulated by stable expression of either miR-143 or miR-145. Further, SOD1 gain-of-function experiments rescued cells from miR-143-induced oxidative stress. Moreover, miR-143 overexpression increased oxaliplatin-induced apoptosis associated with reactive oxygen species generation, which was abrogated by genetic and pharmacological inhibition of oxidative stress. Overall, miR-143 might circumvent resistance of colon cancer cells to oxaliplatin via increased oxidative stress in HCT116 human colon cancer cells.


[Determination of plasma lactoferrin by the "double sandwich" immunoenzymatic method in heterogeneous phase].
For the determination of lactoferrin in human plasma we describe a double-sandwich immunoenzymatic assay in 3 steps using tubes as the solid phase. The analytical performances are acceptable. Within-run and between-run CVs are respectively 4% and 13%, the lower limit of detection is 8 micrograms/l. Sensitivity and specificity are good. The influence on lactoferrin concentration of time elapsing from blood sampling to separation of plasma from cells was studied in order to define the optimal conditions of storage and centrifugation. The range of concentration obtained on 22 healthy adults lies between 59 and 345 micrograms/l.


Repeat abortion: is it a problem?
As the number of Canadian women who have had induced abortions increases with each succeeding year, the number at risk--and the actual incidence--of repeat abortion also increases. Some researchers have argued that women who have more than one induced abortion are less well adjusted, others that they are less willing to use contraceptives, perhaps because of anxiety about sexuality. Still others have suggested that repeat abortion is unrelated to the psychology or attitudes of individual women, but rather is an inevitable result of imperfect contraceptives, imperfect contraceptive practice and the availability of legal abortion for the termination of unwanted pregnancies. A group of 580 women seeking abortions were interviewed at the Montreal General Hospital and given a number of psychological tests. About one in five of these women were having repeat abortions. The women having repeat abortions were older, less likely to be married and more tolerant of legal abortion than were women having their first abortions. They also had intercourse more frequently than the first-abortion patients. Women obtaining a repeat abortion were slightly more likely to have been using contraceptives at the time they became pregnant, but they did not differ from first-abortion patients in the types of methods that they used. On no other social or demographic characteristics, measures of psychological adjustment or attitudes about sexuality were there any important differences between the groups. A more complex statistical analysis reveals that the two most important factors differentiating first-abortion and repeat-abortion patients are age and coital frequency--both of which are variables that reflect added exposure to the risk of unintended pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)


Coexistence of polar and nonpolar domains and their photocontrol in the B7 phase of a bent-core liquid crystal containing azo dyes.
Coexisting polar and nonpolar domains have been studied by means of texture observation, x-ray analysis, optical second-harmonic generation (SHG), and SHG microscopy in the B7 phase of a bent-core mesogen doped with azo dyes. The bent-core molecules take a planar orientation and show high birefringence in the polar domain, while they take a homeotropic orientation and show low birefringence in the nonpolar domain. Good correspondence between real and SHG images was observed under a SHG microscope; the bright (high-birefringent) domain is SHG active and the dark (low-birefringent) domain is not SHG active. Photoisomerization of the azo dyes causes layer reorientation from the layer perpendicular to the substrate to that parallel to it.


Analysis of friction in quantitative micro-elastography.
Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique capable of measuring the mechanical properties of tissue on the micro-scale. As QME requires contact between the imaging window and the sample, the presence of friction affects the accuracy of the estimated elasticity. In previous implementations, a lubricant was applied at the contact surfaces, which was assumed to result in negligible friction. However, recently, errors in the estimation of elasticity caused by friction have been reported. This effect has yet to be characterized and is, therefore, not well understood. In this work, we present a systematic analysis of friction in QME using silicone phantoms. We demonstrate that friction, and, therefore, the elasticity accuracy, is influenced by several experimental factors, including the viscosity of the lubricant, the mechanical contrast between the compliant layer and the sample, and the time after the application of a compressive strain. Elasticity errors over an order of magnitude were observed in the absence of appropriate lubrication when compared to uniaxial compression testing. Using an optimized lubrication protocol, we demonstrate accurate elasticity estimation (<10% error) for nonlinear elastic samples with Young's moduli ranging from 3 kPa to 130 kPa. Finally, using a structured phantom, we demonstrate that friction can significantly reduce mechanical contrast in QME. We believe that the framework established in this study will facilitate more robust elasticity estimations in QME, as well as being readily adapted to understand the effects of friction in other contact elastography techniques.


Growth, not digestibility, in chickens receiving reduced-protein diets is independent of non-specific amino-nitrogen sources when the essential-to-total-nitrogen ratio is constant and lower than 50.
1. A 21 d experiment was conducted to investigate whether growth performance and coefficients of amino acids digestibility (cAID) in broilers receiving reduced-protein diets supplemented with different non-essential amino acids (NEAA) were dependent on supplemented NEAA in diets with the same essential-to-total N (eN-to-tN) ratio kept at <50%.2. The experiment used 240 male broiler chicks, allocated to eight treatments with six replicate pens per treatment, and five chicks per replicate. The diets were either adequate in protein diet (PC), reduced protein (NC) diet or the NC diet supplemented with Gly, Gln, Ser, Ala, Gly + Ser or Ala + Ser. Digesta from the distal half of the ileum were collected on d 21. Tissue samples were collected for analysis for gene expression of protein synthesis and degradation (pectoralis major and liver) and peptide and AA transporters (jejunum).3. The treatments had no effects on growth performance. Generally, cAID was greater (P < 0.05) in NC compared to the PC diet. Individual supplementation of the NC diet with Gly, Gln, Ser, Ala or Ala+Ser increased (P < 0.01) cAID of Cys compared to the PC diet. There were no treatment effects on mRNA levels for the AA or peptide transporters in the jejunum. Supplementation of the NC diet with Gln, Ser, Ala, or Gly + Ser produced an upward expression (P < 0.05) of S6 kinase in the liver compared to PC and NC. In addition, there was greater (P < 0.05) expression of TRIM36 in the pectoralis major of broiler chickens receiving the NC diet supplemented with Gly.4. When reduced-protein diets have an eN-to-tN ratio of <50% and the ratio is kept constant in all the diets, growth performance response was independent of the source of non-specific amino-N, but the treatments may influence ileal digestibility of individual AA.


Human trophoblast function during the implantation process.
The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors. Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment. This review is focused on the molecular constituents of the human trophoblast, their actions and interactions, including interrelations with the uterine endometrium.


Protective effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship with oxidant and antioxidant parameters.
Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. A lot of antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study aimed to investigate the antiulcer effects of mirtazapine and to determine its relationship with antioxidant mechanisms. The antiulcer activities of 15, 30, and 60 mg/kg mirtazapine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Mirtazapine decreased the indomethacin-induced ulcers significantly at all doses used. Mirtazapine significantly increased the glutathione (GSH) level, which decreased in the control group given only indomethacin. All doses of mirtazapine significantly decreased the catalase (CAT) level in stomach tissue compared to the control. Additionally, all doses of mirtazapine reversed the decrease in the superoxide dismutase (SOD) level in the stomach tissue of control rats. And finally, all doses of mirtazapine decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels significantly compared to the control. In conclusion, the activation of enzymatic and non-enzymatic antioxidant mechanisms and the inhibition of some toxic oxidant mechanisms play a role in the antiulcer effect mechanism of mirtazapine. This new indication of mirtazapine will make it the first-choice drug in depressive patients with gastric ulcers.


Coil occlusion of arteriovenous fistula of the vertebral artery in a child.
A 5-year-old boy with congenital fistula between the right vertebral artery and concomitant veins underwent a successful transcatheter fistula occlusion with a Gianturco coil.


Primary structure of the smallest (6.4-kDa) subunit of human and bovine ubiquinol-cytochrome c reductase deduced from cDNA sequences.
Amino acid sequences of the smallest subunit of human and bovine ubiquinol-cytochrome c reductase were deduced from nucleotide sequence of recombinant cDNA clones isolated by screening the corresponding cDNA libraries. Both proteins were composed of 56 amino acids. They were 84% homologous to each other in the coding nucleotide sequences and 88% homologous in the amino acid sequences. Southern blot analysis with human DNA suggested the presence of a single gene coding for the protein. Northern blot of human mRNAs from different tissues confirmed the existence of a single species of transcript among the tissues but the human gene is highly expressed in bioenergetically active tissues like heart and skeletal muscle.


Treated periodontitis and recurrent events after first-time myocardial infarction: A Danish nationwide cohort study.
To investigate the association between previous periodontal treatment and recurrent events after first-time myocardial infarction (MI). From the Danish nationwide registries, patients with first-time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first-time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3-year risk of major adverse cardiovascular events (MACE). A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first-time MI had an adjusted 3-year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92-1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3-year risks of MACE (OR 1.47 [95% CI 1.42-1.52]), cardiovascular death (OR 1.71 [95% CI 1.64-1.78]) and heart failure (OR 1.13 [95% CI 1.07-1.20]) compared with patients presumed periodontally healthy. Patients with treated PD 1 year prior to first-time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first-time MI was an independent risk factor for recurrent events.


A General Approach to Test for Interaction Among Mixtures of Insecticidal Proteins Which Target Different Orders of Insect Pests.
A shift toward transgenic crops which produce combinations of insecticidal proteins has increased the interest (Syngenta Seeds, Inc., Minnetonka, MN) in studying the potential for interactions amongst those proteins. We present a general testing method which accommodates proteins with nonoverlapping spectrums of activity. Our sequential testing approach first investigates groups of the proteins with overlapping activity; e.g., proteins active against Lepidoptera or Coleoptera, respectively. The Colby method is used to test for interactions within each respective group. Subsequently, the mixture of proteins within each group is regarded as a single entity and tests for interactions between the groups (when combined) is conducted using analysis of variance. We illustrate the method using Cry1Ab, Vip3Aa20, and Cry1F (a mixture of proteins active against Lepidoptera), and mCry3A and eCry3.1Ab (a mixture of proteins active against Coleoptera). These insecticidal proteins are produced by Bt11 × MIR162 × TC1507 × MIR604 × 5307 maize. We detected no interactions between Cry1Ab, Vip3Aa20, and Cry1F in tests using larvae of two different lepidopteran species, and possible slight antagonism between mCry3A and eCry3.1Ab with a coleopteran test species. We detected no effect of (eCry3.1Ab + mCry3A) on the potency of (Cry1Ab + Vip3Aa20 + Cry1F) to lepidopteran larvae, and no effect of (Cry1Ab + Vip3Aa20 + Cry1F) on the potency of (mCry3A + eCry3.1Ab) to coleopteran larvae. We discuss implications of these results for characterization of Bt11 × MIR162 × TC1507 × MIR604 × 5307 maize, and the value of the method for characterizing other transgenic crops that produce several insecticidal proteins.


Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?
Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using χ (2) tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription.


Red blood cell storage lesion: causes and potential clinical consequences.
Red blood cells (RBCs) are a specialised organ that enabled the evolution of multicellular organisms by supplying a sufficient quantity of oxygen to cells that cannot obtain oxygen directly from ambient air via diffusion, thereby fueling oxidative phosphorylation for highly efficient energy production. RBCs have evolved to optimally serve this purpose by packing high concentrations of haemoglobin in their cytosol and shedding nuclei and other organelles. During their circulatory lifetimes in humans of approximately 120 days, RBCs are poised to transport oxygen by metabolic/redox enzymes until they accumulate damage and are promptly removed by the reticuloendothelial system. These elaborate evolutionary adaptions, however, are no longer effective when RBCs are removed from the circulation and stored hypothermically in blood banks, where they develop storage-induced damages ("storage lesions") that accumulate over the shelf life of stored RBCs. This review attempts to provide a comprehensive view of the literature on the subject of RBC storage lesions and their purported clinical consequences by incorporating the recent exponential growth in available data obtained from "omics" technologies in addition to that published in more traditional literature. To summarise this vast amount of information, the subject is organised in figures with four panels: i) root causes; ii) RBC storage lesions; iii) physiological effects; and iv) reported outcomes. The driving forces for the development of the storage lesions can be roughly classified into two root causes: i) metabolite accumulation/depletion, the target of various interventions (additive solutions) developed since the inception of blood banking; and ii) oxidative damages, which have been reported for decades but not addressed systemically until recently. Downstream physiological consequences of these storage lesions, derived mainly by in vitro studies, are described, and further potential links to clinical consequences are discussed. Interventions to postpone the onset and mitigate the extent of the storage lesion development are briefly reviewed. In addition, we briefly discuss the results from recent randomised controlled trials on the age of stored blood and clinical outcomes of transfusion.


Classifiers and their Metrics Quantified.
Molecular modeling frequently constructs classification models for the prediction of two-class entities, such as compound bio(in)activity, chemical property (non)existence, protein (non)interaction, and so forth. The models are evaluated using well known metrics such as accuracy or true positive rates. However, these frequently used metrics applied to retrospective and/or artificially generated prediction datasets can potentially overestimate true performance in actual prospective experiments. Here, we systematically consider metric value surface generation as a consequence of data balance, and propose the computation of an inverse cumulative distribution function taken over a metric surface. The proposed distribution analysis can aid in the selection of metrics when formulating study design. In addition to theoretical analyses, a practical example in chemogenomic virtual screening highlights the care required in metric selection and interpretation.


[A CASE OF SOLITARY ADRENAL TUMOR METASTASIZED FROM RECTAL CANCER].
Solitary adrenal metastasis of rectal cancer is comparatively rare condition and it is difficult to be diagnosed because it doesn't have any characteristic symptoms. We report a case of this type of adrenal tumor that could be figured out by tumor markers and the analysis of CT scan image. A 67-year-old man visited our department with the right adrenal tumor. He has a past medical history of rectal cancer and a low anterior resection was performed in 2011. After the surgery, he received adjuvant chemotherapy for 6 months. There has been no finding of recurrence or metastasis after chemotherapy. However, his follow-up abdominal CT in 2013 showed the right adrenal tumor which was 23 mm in diameter. Serum CEA level has also increased to 4.1 ng/ml, but there was no abnormal finding with hormonal study. The tumor size and CEA level gradually increased up to 46 mm in size and 10.4 ng/ml during 6 months. Enhanced CT also showed 39% at rate of absolute percentage wash out, which was not the finding of typical functional adrenal tumor. Based on these findings, we diagnosed that the origin of this adrenal tumor should be solitary metastasis of the rectal cancer. For the treatment of surgical procedure, we performed laparoscopic right adrenalectomy. The pathological finding showed adenocarcinoma, the origin of which was the previous rectal cancer. Six months have passed since the surgery, but CEA level still has remained normal range and neither finding of recurrence nor metastasis has been found.


Respiratory syncytial virus activity--United States, July 2011-January 2013.
Respiratory syncytial virus (RSV) causes lower respiratory infections among infants and young children worldwide. During 1997-2006, an estimated 132,000-172,000 children aged <5 years were hospitalized for RSV infection annually in the United States. In temperate climate zones, RSV generally circulates during the fall, winter, and spring, but the exact timing and duration of RSV seasons vary by region and year. To determine seasonal trends in the circulation of RSV at national and regional levels, data collected by the National Respiratory and Enteric Virus Surveillance System (NREVSS) were analyzed. For 2011-12, the RSV season onset ranged from late October to mid-January and season offset ranged from early March to early May in all 10 U.S. Department of Health and Human Services (HHS) regions, excluding Florida. Florida is reported separately because it has an earlier season onset and longer duration than the rest of the country. For data reported as of January 7, 2013, RSV onset for the 2012-13 season occurred in all but one of the HHS regions by December 15, 2012. Seasonal patterns remained consistent with previous years and demonstrated the usual differences in RSV circulation among HHS regions. Health-care providers and public health officials can use information on RSV circulation to guide diagnostic testing and timing of RSV immunoprophylaxis for children at high risk for severe respiratory infection.


Post-irradiation free radical generation: evidence from the conversion of xanthine dehydrogenase into xanthine oxidase.
The xanthine oxidoreductase (XOR) system which consists of xanthine dehydrogenase (XDH) and xathine oxidase (XO), is one of the major sources of free radicals in biological systems. The XOR system is pre-dominantly present as XDH in normal tissues and converts into the free radical generating XO-form in the damaged tissue. Therefore, the XO-form of the XOR system is expected to be mainly found in radiolytically damaged tissues. In such an event, XO may catalyze the generation of free radicals and potentiate radiation effects in the post-irradiation period. Recent findings on the effect of ionizing radiation on the XOR system in the liver of mice, peroxidative damage and lactate dehydrogenase support this possibility. From these results it has been hypothesized that free radical generating systems could be activated in the radiolytically damaged cell and in turn contribute to the cause and complications of late effects and their persistence in post-irradiation period. This aspect may have great significance in the understanding of radiation-induced damages. It may also have serious implication in various fields like radiation therapy, health physics, carcinogenesis, space travelling radiation exposures and post nuclear accident care. Further, it is suggested that efforts need to be made to search more system(s) which could be activated particularly at lower doses of radiation to generate free radicals in the post-exposure period.


Associations Between Single Nucleotide Polymorphisms of Hypoxia-Related Genes and Capsule Formation in Hepatocellular Carcinoma.
Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated. Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis. A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule. The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.


Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction.
Two general methods for the synthesis of 2-imino-5-carboxy-3,4-dihydropyrimidines were developed using the three-component Biginelli reaction. The first method utilizes pyrazole carboxamidine, a beta-ketoester, and an aldehyde in an initial Biginelli reaction. After Boc protection, these products undergo aminolysis and acidic deprotection to generate 2-imino-5-carboxy-3,4-dihydropyrimidines in a four-step sequence. The second method utilizes a triazone-protected guanidine, a beta-ketoester, and an aldehyde in a Biginelli reaction. Acidic cleavage of the triazone yields 2-imino-5-carboxy-3,4-dihydropyrimidines in a two-step sequence. We also describe the further elaboration of several of these products using a tethered Biginelli reaction to give triazaacenaphthalene structures similar to those found in crambescidin and batzelladine alkaloids.


Integrated bioassays in microfluidic devices: botulinum toxin assays.
A microfluidic assay was developed for screening botulinum neurotoxin serotype A (BoNT-A) by using a fluorescent resonance energy transfer (FRET) assay. Molded silicone microdevices with integral valves, pumps, and reagent reservoirs were designed and fabricated. Electrical and pneumatic control hardware were constructed, and software was written to automate the assay protocol and data acquisition. Detection was accomplished by fluorescence microscopy. The system was validated with a peptide inhibitor, running 2 parallel assays, as a feasibility demonstration. The small footprint of each bioreactor cell (0.5 cm2) and scalable fluidic architecture enabled many parallel assays on a single chip. The chip is programmable to run a dilution series in each lane, generating concentration-response data for multiple inhibitors. The assay results showed good agreement with the corresponding experiments done at a macroscale level. Although the system has been developed for BoNT-A screening, a wide variety of assays can be performed on the microfluidic chip with little or no modification.


Ribosomes terminated in vitro are in a tight association with non-phosphorylated elongation factor 2 (eEF-2) and GDP.
A proportion of the ribosome population in the eukaryotic cell is present in the form of single 80-S ribosomes. These are not involved in translation and are tightly associated with eukaryotic elongation factor 2 (eEF-2). The factor dissociates from ribosomes when it is ADP-ribosylated. Attempts at reconstitution of such complexes from ribosomal subunits and eEF-2 were not successful. We have shown that monomeric ribosomes in a tight complex with eEF-2 can be obtained in vitro as terminated ribosomes in a reconstituted translation system containing isolated polyribosomes, elongation factors and pH5 enzymes (all from rabbit reticulocytes). Incubation of the system with radioactive GTP demonstrated that terminated ribosomes contain GDP. ADP-ribosylation of eEF-2 bound to terminated ribosomes by diphtheria toxin leads to dissociation of both eEF-2 and GDP to the same extent. Thus the presence of GDP in terminated ribosomes is eEF-2 dependent. Ribosomes terminated in vitro as well as native single ribosomes contain the non-phosphorylated form of eEF-2. We assume that tight association of terminated ribosomes with the non-phosphorylated form of eEF-2 excludes both the ribosome and active eEF-2 from the translational cycle and thus, maintains the optimal proportion of translating ribosomes and free eEF-2 in the cell.


Role of HSP70 in motoneuron survival after excitotoxic stress in a rat spinal cord injury model in vitro.
The outcome for gait recovery from paralysis due to spinal lesion remains uncertain even when damage is limited. One critical factor is the survival of motoneurons, which are very vulnerable cells. To clarify the early pathophysiological mechanisms of spinal damage, an in vitro injury model of the rat spinal cord caused by moderate excitotoxicity was used. With this preparation we investigated whether motoneuron survival was dependent on the expression of the neuroprotective protein HSP70. In the present study excitotoxicity evoked by kainate induced delayed (24 h) loss (35%) of motoneurons, which became pyknotic with translocation of the cell death biomarker apoptosis-inducing factor (AIF) to the nucleus. This process was concomitant with suppression of locomotor network electrical activity. Surviving cells showed strong expression of HSP70 without nuclear AIF. The HSP70 inhibitor VER155008 per se induced neurotoxicity similar to that of kainate, while the HSP90 inhibitor geldanamycin did not damage spinal tissue. Electrophysiological recording following kainate or VER155008 indicated depression of motoneuron field potentials, with decreased excitability and impaired synaptic transmission. When these two drugs were applied together, more intense neurotoxicity emerged. Our data indicate that HSP70 was one important contributor to motoneuron survival and suggest that enhancing HSP70 activity is a potential future strategy for neuroprotecting these cells.


Loss of CABLES1, a cyclin-dependent kinase-interacting protein that inhibits cell cycle progression, results in germline expansion at the expense of oocyte quality in adult female mice.
Recent studies have shown that cell cycle inhibitors encoded by the Ink4a gene locus constrain the self-renewing activity of adult stem cells of the hematopoietic and nervous systems. Here we report that knockout (KO) of the Cables1 [cyclin-dependent kinase (CDK)-5 and ABL enzyme substrate 1] cell cycle-regulatory gene in mice has minimal to no effect on hematopoietic stem cell (HSC) dynamics. However, female Cables1-null mice exhibit a significant expansion of germ cell (oocyte) numbers throughout adulthood. This is accompanied by a dramatic elevation in the number of atretic immature oocytes within the ovaries and an increase in the incidence of degenerating oocytes retrieved following superovulation of CABLES1-deficient females. These outcomes are not observed in mice lacking p16INK4a alone or both p16INK4a and p19ARF. These data support recent reports that adult female mice can generate new oocytes and follicles but the enhancement of postnatal oogenesis by Cables1 KO appears offset by a reduction in oocyte quality, as reflected by increased elimination of these additional germ cells via apoptosis. This work also reveals cell lineage specificity with respect to the role that specific CDK-interacting proteins play in restraining the activity of adult germline versus somatic stem cells.


Recanalization of Acute Common Carotid Artery Occlusion: 2-Dimensional Operative Video.
While revascularization of the acutely or chronically occluded internal carotid artery has become commonplace with modern endovascular techniques, revascularization of an acutely occluded common carotid artery (CCA) is a controversial procedure with unique challenges. These challenges can be related to the lack of observable markers for identifying vessels during navigation or for identifying the exact location and extent of occlusion within the CCA, in addition to wide-ranging treatment risks. In this video, we illustrate the controversial revascularization of a 68-yr-old woman with an acute CCA occlusion who presented with fluctuating neurological symptoms. We believed treatment to be indicated by the lack of adequate collaterals on the intracranial CTA, and fluctuating symptoms in the absence of an intracranial major vessel occlusion, suggesting that the CCA occlusion was exerting important hemodynamic effects and at risk of causing a major stroke without revascularization, despite a low initial NIH stroke score. Though acute recanalization of patients with low NIH stroke score with stent-angioplasty is a controversial procedure, we believed it to be necessary in the case of our patient and believe it will likely be the focus of the next wave of large clinical trials dedicated to acute stroke.


Diffuse sclerosing variant of papillary carcinoma of the thyroid. Report of three cases.
Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.


Predissociation and dissociative ionization of Rydberg states of Xe2 and the photodissociation of Xe2+.
The Rydberg states of Xe(2) in the region between 76,000 and 84,000 cm(-1) were studied by using a combination of two-photon excitation and velocity map ion imaging. The electronic states in this region are based on the Xe((1)S(0))+Xe 6p and 5d dissociation limits, and the large number of states leads to numerous curve crossings and distorted potentials. These Rydberg states can decay by predissociation or fluorescence or can be photoionized, dissociatively photoionized, or photodissociated by the absorption of a single additional photon. Furthermore, the molecular ion can be photodissociated as well. While numerous other techniques have been applied to this problem, velocity map ion imaging provides a high resolution approach to determine the operative processes. When combined with existing data obtained by other methods, the present experiments allow a more complete understanding of the assignment and behavior of these states.


Crosstalk Between MAPK/ERK and PI3K/AKT Signal Pathways During Brain Ischemia/Reperfusion.
The epidermal growth factor receptor (EGFR) is linked to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Raf/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling pathways. During brain ischemia/reperfusion, EGFR could be transactivated, which stimulates these intracellular signaling cascades that either protect cells or potentiate cell injury. In the present study, we investigated the activation of EGFR, PI3K/AKT, and Raf/MAPK/ERK1/2 during ischemia or reperfusion of the brain using the middle cerebral artery occlusion model. We found that EGFR was phosphorylated and transactivated during both ischemia and reperfusion periods. During ischemia, the activity of PI3K/AKT pathway was significantly increased, as judged from the strong phosphorylation of AKT; this activation was suppressed by the inhibitors of EGFR and Zn-dependent metalloproteinase. Ischemia, however, did not induce ERK1/2 phosphorylation, which was dependent on reperfusion. Coimmunoprecipitation of Son of sevenless 1 (SOS1) with EGFR showed increased association between the receptor and SOS1 in ischemia, indicating the inhibitory node downstream of SOS1. The inhibitory phosphorylation site of Raf-1 at Ser259, but not its stimulatory phosphorylation site at Ser338, was phosphorylated during ischemia. Furthermore, ischemia prompted the interaction between Raf-1 and AKT, while both the inhibitors of PI3K and AKT not only abolished AKT phosphorylation but also restored ERK1/2 phosphorylation. All these findings suggest that Raf/MAPK/ERK1/2 signal pathway is inhibited by AKT via direct phosphorylation and inhibition at Raf-1 node during ischemia. During reperfusion, we observed a significant increase of ERK1/2 phosphorylation but no change in AKT phosphorylation. Inhibitors of reactive oxygen species and phosphatase and tensin homolog restored AKT phosphorylation but abolished ERK1/2 phosphorylation, suggesting that the reactive oxygen species-dependent increase in phosphatase and tensin homolog activity in reperfusion period relieves ERK1/2 from inhibition of AKT.


Substitution of cane molasses for corn grain at two levels of degradable protein. I. Lactating cow performance, nutrition model predictions, and potential basis for butterfat and intake responses.
Little data is presently available on our ability to predict the combined effect of modifying diets with feeds rich in sugars or starch (ST) and rumen-degradable protein (RDP) on the performance of high-producing dairy cows. The objective of this study was to compare responses of 59 lactating Holstein cows to substitution of cane molasses (Mol) for dry corn grain (CG) at 3 levels of Mol and 2 levels of RDP (+RDP or -RDP) in a randomized complete block design with a 3 × 2 factorial arrangement of treatments. Also, lactation responses predicted by 2 nutritional models were compared with observed responses, with Mol composition entered so that nonnutritive materials in Mol were not counted as potentially digestible carbohydrate. We hypothesized that dry matter (DM) intake and milk fat percentage responses would increase with increasing Mol and would potentially be greater with +RDP. For evaluation of the nutritional models, we adopted the null hypothesis that observed and predicted lactation performance would not differ. Cows were individually fed a common diet during a 2-wk covariate period followed by 8 wk on experimental diets. Diets were formulated to be isonitrogenous and provide similar amounts of ST and water-soluble carbohydrates. Experimental diets contained, on a DM basis, 35% corn silage, 20% alfalfa silage, and 16.6% crude protein. The 0, 5.25, and 10.5% Mol diets respectively contained 19.0, 14.5, and 10.0% CG; 28, 25, and 22% ST; and 5.5, 8.5, and 11.5% water-soluble carbohydrates. At 10 wk on study, cows averaged 45.5 kg of energy-corrected milk (ECM). The DM intake (DMI), and yields of milk, milk protein, and ECM, and milk N/intake N declined linearly with increasing Mol. Differences among diets were not detected for milk fat yield and ECM/DMI. No RDP or interaction effects were detected for these measures. That milk production efficiency did not differ across diets suggests that DMI was a primary driver of performance. The similar ECM/DMI and maintenance of milk fat yield would not have been predicted based on Mol and CG composition but may relate to differences in fermentation rates and products. As explanation for these results, we hypothesize that more rapid ruminal evolution of volatile fatty acids post-ingestion with Mol compared with CG may have provided masses of acetate and butyrate in excess of existing energy and synthetic needs that were shunted to milk fat production, and of propionate that depressed intake. The 2001 Dairy National Research Council model and the Cornell Net Carbohydrate and Protein System 6.55 in Nutritional Dynamic System Professional (2021) estimates of metabolizable protein-allowable ECM underestimated actual ECM for +RDP diets by 4.5 and 2.3 kg, respectively, and came close or overestimated for -RDP diets by 0.25 and 5.0 kg, respectively. Prediction discrepancies suggest issues with valuation of dietary protein based on degradability. Improved understanding of factors mediating these results would likely enhance our ability to predict animal responses.


Li[B(OCH2CF3)4]: synthesis, characterization and electrochemical application as a conducting salt for LiSB batteries.
A new Li salt with views to success in electrolytes is synthesized in excellent yields from lithium borohydride with excess 2,2,2-trifluorethanol (HOTfe) in toluene and at least two equivalents of 1,2-dimethoxyethane (DME). The salt Li[B(OTfe)4 ] is obtained in multigram scale without impurities, as long as DME is present during the reaction. It is characterized by heteronuclear magnetic resonance and vibrational spectroscopy (IR and Raman), has high thermal stability (Tdecomposition >271 °C, DSC) and shows long-term stability in water. The concentration-dependent electrical conductivity of Li[B(OTfe)4 ] is measured in water, acetone, EC/DMC, EC/DMC/DME, ethyl acetate and THF at RT In DME (0.8 mol L(-1) ) it is 3.9 mS cm(-1) , which is satisfactory for the use in lithium-sulfur batteries (LiSB). Cyclic voltammetry confirms the electrochemical stability of Li[B(OTfe)4 ] in a potential range of 0 to 4.8 V vs. Li/Li(+) . The performance of Li[B(OTfe)4 ] as conducting salt in a 0.2 mol L(-1) solution in 1:1 wt % DME/DOL is investigated in LiSB test cells. After the 40th cycle, 86 % of the capacity remains, with a coulombic efficiency of around 97 % for each cycle. This indicates a considerable performance improvement for LiSB, if compared to the standard Li[NTf2 ]/DOL/DME electrolyte system.


[Comparative study of the effect of famotidine and cimetidine on antipyrine pharmacokinetics in the human].
In a randomized order the pharmacokinetics of antipyrine were studied following a 5 days treatment period with placebo, 1000 mg cimetidine and 40 mg famotidine daily, respectively in 7 healthy volunteers. In contrast to cimetidine, famotidine did not significantly affect the disposition of antipyrine in these subjects. Famotidine like the other guanidino-thiazole containing compound tiotidine appears to be free from this unwanted effect on drug metabolism in the liver.


A qualitative inquiry into consumer beliefs about the causes of mental illness.
This paper examines consumer or service user beliefs about the causes of mental illness. It presents a qualitative, participatory action research study involving semi-structured in-depth interviews with 16 people who had been diagnosed with a mental illness and attended a community mental health centre in metropolitan South Australia. Inductive thematic analysis was undertaken, with a range of beliefs about the possible cause of mental illness identified. Findings are organized within two key areas: social or environmental factors and physical or biological factors. The social or environmental category included varied situations, clustered under the subcategories of: stress during childhood, events in adulthood and religious beliefs. Physical or biological factors included beliefs that mental illness was inherited, caused by brain malfunction or chemical imbalance. Of note, one-third of consumer participants who discussed possible causes of mental illness identified multiple potential causes. Implications for service delivery, specifically related to therapeutic trust and engagement, are also considered.


Enzymatic oxidation of ethanol in the gaseous phase.
The enzymatic conversion of gaseous substrates represents a novel concept in bioprocessing. A critical parameter in such systems is the water activity, A(w) The present article reports the effect of A(w) on the catalytic performance of alcohol oxidase acting on ethanol vapors. Enzyme activity in the gas-phase reaction increases several orders of magnitude, whereas the thermostability decreases drastically when A(w) is increased from 0.11 to 0.97. The enzyme is active on gaseous substrates even at hydration levels below the monolayer coverage. Enhanced thermostability at lower hydrations results in an increase in the optimum temperature of the gas-phase reaction catalyzed by alcohol oxidase. The apparent activation energy decreases as A(w) increases, approaching the value obtained for the enzyme in aqueous solution. The formation of a pread-sorbed ethanol phase on the surface of the support is not a prerequisite for the reaction, suggesting that the reaction occurs by direct interaction of the gaseous substrate with the enzyme. The gas-phase reaction follows Michaelis-Menten kinetics, with a K(m) value almost 100 times lower than that in aqueous solution. Based on vapor-liquid equilibrium data and observed K(m) values, it is postulated that during the gas-phase reaction the ethanol on the enzyme establishes an equilibrium with the ethanol vapor similar to that between ethanol in water and ethanol in the gas phase.


Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti cancer drug delivery.
Interpenetrating polymeric network nanogels (IPN-NGs) composed of natural gelatin biological protein macromolecules and poly(acrylamidoglycolic acid) were produced by simple free radical emulsion polymerization. The developed IPN-NGs were characterized by Fourier-transform infra-red spectroscopy to confirm the formation of NGs. The hydrophobic curcumin drug was loaded successfully into these NGs using an in-situ method. The curcumin-encapsulated NGs were well dispersed in aqueous solutions and showed good bioavailability. Curcumin was dispersed molecularly in the IPN-NGs, which was confirmed by differential scanning calorimetry and X-ray diffraction. The NGs exhibited pH sensitive properties according to dynamic light scattering and the zeta size potentials. Transmission electron microscopy revealed the NGs to be spherical, approximately 100nm in size. The encapsulation efficiency of these IPN-NGs drug formulations ranged from 42 to 48%. In addition, the release of curcumin from the NGs was examined in phosphate buffer medium. The cytotoxicity of the IPN-NGs was studied using in vitro cultures of fibroblasts and a colorectal cancer cell line. The results suggest that the newly developed pH sensitive gelatin-poly(acrylamidoglycolic acid)-curcumin NGs can be applied for colorectal cancer drug delivery applications.


Effect of Propranolol Alone and in Combination with Pyrimethamine on Acute Murine Toxoplasmosis.
Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs. In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo. This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n = 3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, pyrimethamine at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus pyrimethamine, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1 × 10(3) tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate. In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with pyrimethamine was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and pyrimethamine (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526 ± 171.4 and 2948 ± 1452.8, respectively, compared with pyrimethamine treatment outcome, which represents 99.9% growth inhibition. Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of pyrimethamine in combination therapies.


Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo.
Astrocytes from familial amyotrophic lateral sclerosis (ALS) patients or transgenic mice are toxic specifically to motor neurons (MNs). It is not known if astrocytes from sporadic ALS (sALS) patients cause MN degeneration in vivo and whether the effect is specific to MNs. By transplanting spinal neural progenitors, derived from sALS and healthy induced pluripotent stem cells (iPSCs), into the cervical spinal cord of adult SCID mice for 9 months, we found that differentiated human astrocytes were present in large areas of the spinal cord, replaced endogenous astrocytes, and contacted neurons to a similar extent. Mice with sALS but not non-ALS cells showed reduced non-MNs numbers followed by MNs in the host spinal cord. The surviving MNs showed reduced inputs from inhibitory neurons and exhibited disorganized neurofilaments and aggregated ubiquitin. Correspondingly, mice with sALS but not non-ALS cells showed declined movement deficits. Thus, sALS iPSC-derived astrocytes cause ALS-like degeneration in both MNs and non-MNs.


NeuSort: an automatic adaptive spike sorting approach with neuromorphic models.
Objective.Spike sorting, a critical step in neural data processing, aims to classify spiking events from single electrode recordings based on different waveforms. This study aims to develop a novel online spike sorter, NeuSort, using neuromorphic models, with the ability to adaptively adjust to changes in neural signals, including waveform deformations and the appearance of new neurons.Approach.NeuSort leverages a neuromorphic model to emulate template-matching processes. This model incorporates plasticity learning mechanisms inspired by biological neural systems, facilitating real-time adjustments to online parameters.Results.Experimental findings demonstrate NeuSort's ability to track neuron activities amidst waveform deformations and identify new neurons in real-time. NeuSort excels in handling non-stationary neural signals, significantly enhancing its applicability for long-term spike sorting tasks. Moreover, its implementation on neuromorphic chips guarantees ultra-low energy consumption during computation.Significance.NeuSort caters to the demand for real-time spike sorting in brain-machine interfaces through a neuromorphic approach. Its unsupervised, automated spike sorting process makes it a plug-and-play solution for online spike sorting.