Comparison of reinjection thallium 201 and resting technetium 99m sestamibi tomographic images for the quantification of infarct size after acute myocardial infarction.
Both thallium 201 and technetium 99m sestamibi have been used to quantitate infarct size at rest. Exercise 201Tl scintigraphy has been shown to have powerful prognostic information after myocardial infarction. A single study using these agents that could provide data on infarct size and prognosis would be of value. The purpose of this study was to compare estimates of infarct size by use of 201Tl and 99mTc sestamibi and to correlate these measurements with left ventricular ejection fraction in patients after acute myocardial infarction. The study group consisted of 20 patients who underwent low-level 201Tl stress studies with reinjection and 99mTc sestamibi resting studies within 4 days. Acute reperfusion was attempted in 18 of 20 patients. For 99mTc sestamibi tomographic imaging, infarct size was quantitated with 60% of maximal counts per slice for five short-axis slices as described in multiple previous studies. The postreinjection delayed 201Tl images acquired 4 hours after stress were quantitated according to the same threshold method. 201Tl patient images were also quantitated with a commercially available polar map program and compared with sex-matched control subjects. Ejection fraction was determined for each patient by radionuclide ventriculography 6 weeks later. Ejection fraction was well preserved for the group: mean 0.53 +/- 0.10. Infarct size with 99mTc sestamibi was 12% +/- 13% of the left ventricle, which was significantly smaller than either method with 201Tl: threshold method, 29% +/- 18% of left ventricle; polar map method, 25% +/- 17% of left ventricle (both 201Tl estimates, p < 0.0001 vs 99mTc sestamibi; 201Tl, 70% threshold vs 201Tl polar map, p = 0.04). There was a significant correlation between infarct size with 99mTc sestamibi and that with 201Tl (r = 0.72 to 0.73; p < 0.001). Infarct size with 99mTc sestamibi, however, provided the closest correlation with ejection fraction (r = 0.81; p < 0.001), with the two 201Tl quantitative methods providing very similar correlations (r = 0.69; p < 0.001). Infarct size with reinjection 201Tl imaging correlates significantly with resting infarct size with 99mTc sestamibi, although it provides significantly larger estimates. Although both approaches can be combined with a same-day exercise protocol, the closer correlation of infarct size with ejection fraction at 6 weeks suggests that resting infarct size with 99mTc sestamibi may be slightly more accurate.


A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme.
Combining bevacizumab with irinotecan is a new chemotherapy regimen for patients with recurrent glioblastoma multiforme (GBM). Recent phase II trials suggest that this combined chemotherapy is beneficial to patients, but the subsequent adverse events may lead to treatment discontinuation. No comparison has yet demonstrated conclusively that the combined chemotherapy is more beneficial than single-agent chemotherapy. Thus, a meta-analysis was conducted to assess the efficacy and safety of bevacizumab compared to bevacizumab combined with irinotecan for the treatment of recurrent GBM. A total of 480 patients were included in the study, with 183 patients (38.1%) in the bevacizumab group and 297 patients (61.9%) in the bevacizumab plus irinotecan group. The median overall survival was 8.63 months (95% confidence interval [CI], 8.54-8.72 months) and 8.91 months (95% CI, 8.69-9.13 months), respectively. The mean objective response rate (complete response plus partial response rate) was 33.9% (95% CI, 18.1-52.1%) and 45.8% (95% CI, 28.2-66.7%), respectively. The 6-month progression-free survival rates (PFS-6) were 38.8% (95% CI, 18.8-57.0%) and 48.3% (95% CI, 25.4-54.3%), respectively. The rate of discontinuation was 5.5% and 20.0%, respectively. Compared with patients treated with bevacizumab only, those in the bevacizumab plus irinotecan group had higher PFS-6 (p=0.046), objective response (p=0.013) and rate of discontinuation (p=0.000) but there was no statistically significant difference in overall survival between the groups (p=0.487). Thus, although the combination of bevacizumab and irinotecan may increase the rate of discontinuation, it provided no obvious improvement in overall survival in patients with recurrent GBM. Therefore, the benefits of drug combination are outweighed by the treatment discontinuity and quality of life effects of drug toxicity and should be considered on an individual patient basis only.


[Glucocorticosteroids in the treatment of acute neurosensory hearing loss. The current state of the problem. Part 2].
Modern literature data are presented on the choice of a drug for hormonal therapy in acute neurosensory hearing loss of various origins, the doses used for systemic therapy, the features and methods of intratympanic administration of glucocorticosteroids, and the evaluation of the effectiveness of treatment with this group of drugs.


Design and Construction of a Cost-Effective Spinning Disk System for Live Imaging of Inner Ear Tissue.
Confocal imaging of fluorescent probes offers a powerful, non-invasive tool which enables data collection from vast population of cells at high spatial and temporal resolution. Spinning disk confocal microscopy parallelizes the imaging process permitting the study of dynamic events in populations of living cells on the millisecond time scale. Several spinning disk microscopy solutions are commercially available, however these are often poorly configurable and relatively expensive. This chapter describes a procedure to assemble a cost-effective homemade spinning disk system for fluorescence microscopy, which is highly flexible and easily configurable. We finally illustrate a reliable protocol to obtain high-quality Ca(2+) and voltage imaging data from cochlear preparations.


Learning disabilities in a population-based group of children with hydrocephalus.
To assess cognitive functions in a population-based group of children with hydrocephalus and to analyse differences between children with and without myelomeningocoele (MMC); with hydrocephalus already present at birth and those who developed it later; children born at full term and those born preterm. Of 103 children with hydrocephalus born in the western-Swedish region in 1989-1993, 73 were assessed using the Wechsler Intelligence Scales or the Griffith Developmental Scales. One-third of the children were normally gifted (IQ >85), another 30% had a low average IQ of 70-84 and 37% had learning disabilities with an IQ of <70. The median IQ was 75, verbal IQ 90 and performance IQ 76 (p<0.001). An IQ of <70 was found in 19 of 45 (42%) children without MMC and in 8 of 28 (29%) of those with MMC. Children born preterm had a lower IQ of 68 than those born at full term with an IQ of 76, while children with hydrocephalus present at birth but without MMC had a lower IQ of 60 than the others with an IQ of 77. Children with cerebral palsy and/or epilepsy (n=22) had a lower IQ of 66 than the IQ of 78 in those without these impairments (p<0.01). Cognitive functions in children with hydrocephalus need to be carefully assessed before school age to ensure adequate support and education. Even the one-third near normally gifted children with an IQ of 70-85 require special attention, due to the profile of relatively well-preserved verbal functions but greatly impaired perceptual and non-verbal abilities.


Dynamic stereotypes of African, Latinx, and White Americans.
Two studies examined how young adults from historically advantaged (Study 1) and disadvantaged (Studies 1 and 2) racial groups perceived agentic and communal traits of their group over time. Consistent with previous research on dynamic stereotypes of gender, disadvantaged groups were expected to perceive significant gains in agentic traits from the past to the present. This tendency was expected to increase with ethnic identification. In Study 1, White American (n = 226) and African and Latinx American (n = 60) students at a predominantly White private college in the Midwestern United States participated in an online survey. In Study 2, African American (n = 137) and Latinx American (n = 167) young adults were recruited primarily via an online platform (www.prolific.co) to complete an online survey. In both studies, African and Latinx Americans attributed significantly lower levels of agency to past ingroup members than to present members. Although ethnic identification was not correlated with the difference between present and past agencies, it was more strongly correlated with present agency than with past agency for both groups. These patterns were not observed among White Americans. Similar to women, African and Latinx Americans perceived significant gains in agentic traits of their group members from the past to the present. These perceptions may serve the needs of historically disadvantaged groups for a positive social identity by affirming how far the ingroup has come. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Relationship of growth temperature and thermotropic lipid phase changes in cytoplasmic and outer membranes from Escherichia coli K12.
Purified cytoplasmic and outer membranes isolated from cells of wild type Escherichia coli grown at 12, 20, 37 and 43 degrees C were labelled with the fatty acid spin probe 5-doxyl stearate. Electron spin resonance spectroscopy revealed broad thermotropic phase changes. The inherent viscosity of both membranes was found to increase as a function of elevated growth temperature. The lipid order to disorder transition in the outer membrane but not the cytoplasmic membrane was dramatically affected by the temperature of growth. As a result, the cytoplasmic membrane presumably existed in a gel + liquid crystalline state during cellular growth at 12 and 20 degrees C, but in a liquid crystalline state when cells were grown at 37 and 43 degrees C. In contrast, the outer membrane apparently existed in a gel + liquid crystalline state at all incubation temperatures. Data presented here indicate that the temperature range over which the cell can maintain the outer membrane phospholipids in a mixed (presumedly gel + liquid crystalline) state correlates with the temperature range over which growth occurs.


Preparation of thin-sections of painting fragments: classical and innovative strategies.
For more than a century, the analyses of painting fragments have been carried out mainly through the preparation of thick resin-embedded cross-sections. Taking into account the development of innovative micro-analytical imaging techniques, alternatives to this standard preparation method are considered. Consequently, dedicated efforts are required to develop preparation protocols limiting the risks of chemical interferences (solubilisation, reduction/oxidation or other reactions) which modify the sample during its preparation, as well as the risks of analytical interferences (overlap of detected signals coming from the sample and from materials used in the preparation). This study focuses particularly on the preparation of thin-sections (1-20 μm) for single or combined fourier transform infrared (FTIR) spectroscopy and X-ray 2D micro-analysis. A few strategies specially developed for the μFTIR analysis of painting cross-sections have already been reported and their potential extrapolation to the preparation of thin-sections is discussed. In addition, we propose two new specific methods: (i) the first is based on a free-embedding approach, ensuring a complete chemical and analytical neutrality. It is illustrated through application on polymeric design objects corpus; (ii) the second is based on a barrier coating approach which strengthens the sample and avoids the penetration of the resin into the sample. The barrier coating investigated is a silver chloride salt, an infrared transparent material, which remains malleable and soft after pellet compression, enabling microtoming. This last method was successfully applied to the preparation of a fragment from a gilded Chinese sculpture (15th C.) and was used to unravel a unique complex stratigraphy when combining μFTIR and μXRF.


Recombinase-independent chromosomal rearrangements between dispersed inverted repeats in Saccharomyces cerevisiae meiosis.
DNA double-strand break (DSB) repair by homologous recombination (HR) uses a DNA template with similar sequence to restore genetic identity. Allelic DNA repair templates can be found on the sister chromatid or homologous chromosome. During meiotic recombination, DSBs preferentially repair from the homologous chromosome, with a proportion of HR events generating crossovers. Nevertheless, regions of similar DNA sequence exist throughout the genome, providing potential DNA repair templates. When DSB repair occurs at these non-allelic loci (termed ectopic recombination), chromosomal duplications, deletions and rearrangements can arise. Here, we characterize in detail ectopic recombination arising between a dispersed pair of inverted repeats in wild-type Saccharomyces cerevisiae at both a local and a chromosomal scale-the latter identified via gross chromosomal acentric and dicentric chromosome rearrangements. Mutation of the DNA damage checkpoint clamp loader Rad24 and the RecQ helicase Sgs1 causes an increase in ectopic recombination. Unexpectedly, additional mutation of the RecA orthologues Rad51 and Dmc1 alters-but does not abolish-the type of ectopic recombinants generated, revealing a novel class of inverted chromosomal rearrangement driven by the single-strand annealing pathway. These data provide important insights into the role of key DNA repair proteins in regulating DNA repair pathway and template choice during meiosis.


Native mass spectrometry identifies an alternative DNA-binding pathway for BirA from Staphylococcus aureus.
An adequate supply of biotin is vital for the survival and pathogenesis of Staphylococcus aureus. The key protein responsible for maintaining biotin homeostasis in bacteria is the biotin retention protein A (BirA, also known as biotin protein ligase). BirA is a bi-functional protein that serves both as a ligase to catalyse the biotinylation of important metabolic enzymes, as well as a transcriptional repressor that regulates biotin biosynthesis, biotin transport and fatty acid elongation. The mechanism of BirA regulated transcription has been extensively characterized in Escherichia coli, but less so in other bacteria. Biotin-induced homodimerization of E. coli BirA (EcBirA) is a necessary prerequisite for stable DNA binding and transcriptional repression. Here, we employ a combination of native mass spectrometry, in vivo gene expression assays, site-directed mutagenesis and electrophoretic mobility shift assays to elucidate the DNA binding pathway for S. aureus BirA (SaBirA). We identify a mechanism that differs from that of EcBirA, wherein SaBirA is competent to bind DNA as a monomer both in the presence and absence of biotin and/or MgATP, allowing homodimerization on the DNA. Bioinformatic analysis demonstrated the SaBirA sequence used here is highly conserved amongst other S. aureus strains, implying this DNA-binding mechanism is widely employed.


Ultra High-Speed Radio Frequency Switch Based on Photonics.
Microwave switches, or Radio Frequency (RF) switches have been intensively used in microwave systems for signal routing. Compared with the fast development of microwave and wireless systems, RF switches have been underdeveloped particularly in terms of switching speed and operating bandwidth. In this paper, we propose a photonics based RF switch that is capable of switching at tens of picoseconds speed, which is hundreds of times faster than any existing RF switch technologies. The high-speed switching property is achieved with the use of a rapidly tunable microwave photonic filter with tens of gigahertz frequency tuning speed, where the tuning mechanism is based on the ultra-fast electro-optics Pockels effect. The RF switch has a wide operation bandwidth of 12 GHz and can go up to 40 GHz, depending on the bandwidth of the modulator used in the scheme. The proposed RF switch can either work as an ON/OFF switch or a two-channel switch, tens of picoseconds switching speed is experimentally observed for both type of switches.


Model-Based Estimation of the Attributable Risk: A Loglinear Approach.
This paper considers model-based methods for estimation of the adjusted attributable risk (AR) in both case-control and cohort studies. An earlier review discussed approaches for both types of studies, using the standard logistic regression model for case-control studies, and for cohort studies proposing the equivalent Poisson model in order to account for the additional variability in estimating the distribution of exposures and covariates from the data. In this paper we revisit case-control studies, arguing for the equivalent Poisson model in this case as well. Using the delta method with the Poisson model, we provide general expressions for the asymptotic variance of the AR for both types of studies. This includes the generalized AR, which extends the original idea of attributable risk to the case where the exposure is not completely eliminated. These variance expressions can be easily programmed in any statistical package that includes Poisson regression and has capabilities for simple matrix algebra. In addition, we discuss computation of standard errors and confidence limits using bootstrap resampling. For cohort studies, use of the bootstrap allows binary regression models with link functions other than the logit.


Drinking in the injury event: a comparison of Mexican-American male ER patients in the United States and in Mexico.
Probability samples of 66 Mexican-American injured male emergency room (ER) patients in Santa Clara County, CA, and 457 injured male ER patients in Pachuca, Mexico are compared on a number of drinking-in-the-event variables. While those in Pachuca were more likely to be positive on the breathalyzer than those in Santa Clara, they were less likely to attribute a causal association of their drinking with the event. Site (Santa Clara) was found to be a significant (positive) predictor of drinking prior to injury.


Reduced interhemispheric inhibition in mild cognitive impairment.
In mild cognitive impairment (MCI), the corpus callosum is known to be affected structurally. We evaluated callosal function by interhemispheric inhibition (IHI) using transcranial magnetic stimulation (TMS) in MCI patients. We investigated 12 amnestic MCI patients and 16 healthy age-matched control subjects. The IHI was studied with a paired-pulse TMS technique. The conditioning TMS was given over the right primary motor cortex (M1) and the test TMS over the left M1. Motor evoked potentials were recorded from the relaxed first dorsal interosseous muscle. We also studied other motor cortical circuit functions; short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Both the amount of IHI and SAI were significantly reduced in MCI patients as compared with control subjects, whereas SICI or ICF did not differ between them. The degree of IHI significantly correlated with neither the mini-mental state examination score nor the degree of SAI. Our results suggest that transcallosal connection between bilateral M1 is primarily involved in MCI, regardless of SAI dysfunction.


Purification, cloning and functional differences of a third fructan 1-exohydrolase (1-FEHw3) from wheat (Triticum aestivum).
A third fructan exohydrolase isoform (1-FEHw3) was purified from wheat stems by a combination of ammonium sulfate precipitation, ConA affinity and ion-exchange chromatography. Homogeneity of the preparation was indicated by the presence of a single band (70 kDa) after SDS-PAGE. The enzyme hydrolyzed mainly beta2-1 linkages in fructans and was inhibited by sucrose. A cDNA could be obtained after reverse transcriptase polymerase chain reaction (RT-PCR)-based strategies and screening of a cDNA library. Functionality tests of the cDNA performed after heterologous expression in the yeast Pichia pastoris showed that the encoded protein has essentially the same characteristics as the native enzyme. Homology with previously described 1-FEH isoforms from wheat was high (97% identity), and the enzyme showed minor differences to the previously published enzymes. The relative abundance of 1-FEH transcripts in different tissues was investigated by using quantitative RT-PCR.


Effect of clofibrate on in vivo triglyceride production and clearance in genetically hyperlipemic rats.
Seventeen hyperlipemic and 17 normolipemic littermate Zucker rats were treated with clofibrate or normal saline to determine the effect of this drug upon hepatic triglyceride (TG) production and peripheral TG disposal. Peripheral Intralipid clearance was not different in hyperlipemic rats relative to control animals. Hyperlipemic animals demonstrated abnormally elevated TG production in the fasted state which was not corrected with clofibrate administration. Following treatment, peripheral Intralipid clearance was increased 100% in hyperlipemic rats, but unchanged in normolipemic animals. These observations provide further evidence that the predominant lipid reducing action of clofibrate is manifested only in the hyperlipemic state, and predominantly upon peripheral lipid disposal.


Reduction in the endogenous arginine decarboxylase transcript levels in rice leads to depletion of the putrescine and spermidine pools with no concomitant changes in the expression of downstream genes in the polyamine biosynthetic pathway.
We investigated whether down-regulation of arginine decarboxylase (ADC) activity and concomitant changes in polyamine levels result in changes in the expression of downstream genes in the polyamine pathway. We generated transgenic rice (Oryza sativa L.) plants in which the rice adc gene was down-regulated by expression of its antisense oat (Avena sativa L.) ortholog. Plants expressed the oat mRNA adc transcript at different levels. The endogenous transcript was down-regulated in five out of eight plant lineages we studied in detail. Reduction in the steady-state rice adc mRNA levels resulted in a concomitant decrease in ADC activity. The putrescine and spermidine pool was significantly reduced in plants with lower ADC activity. Expression of the rice ornithine decarboxylase (odc), S-adenosylmethionine decarboxylase (samdc) and spermidine synthase (spd syn) transcripts was not affected. We demonstrate that even though levels of the key metabolites in the pathway were compromised, this did not influence steady-state transcription levels of the other genes involved in the pathway. Our results provide an insight into the different regulatory mechanisms that control gene expression in the polyamine biosynthetic pathway in plants by demonstrating that the endogenous pathway is uncoupled from manipulations that modulate polyamine levels by expression of orthologous transgenes.


Preliminary evaluation of the Polish tissue adhesive "Chirurcoll/Polfa" in urology.
During the past two years, from June 7, 1974 to August 9, 1976, the authors used the Polish tissue adhesive "Chirurcoll/Polfa" in 60 operated patients. The operations were performed on the solitary kidney, on the kidneys of staghorn calculi, in fixation of a floating kidney and, fixation and elevation of the bladder in women with urinary stress incontinence. In all cases the postoperative course was smooth and the results of operation were satisfactory. None of the patients were re-operated and histological examinations were not performed.


Combined use of iliac artery angioplasty and infrainguinal revascularization for treatment of multilevel atherosclerotic disease.
The purpose of this report is to review our recent experience with the combined use of iliac artery angioplasty and infrainguinal surgical revascularization for the treatment of multilevel atherosclerotic disease. A retrospective review of all patients with multilevel atherosclerotic disease who were treated with both iliac artery angioplasty and infrainguinal bypass surgery during a 4-year period was performed. The medical records and preoperative arteriograms of all patients were reviewed for demographic information, radiologic findings, and postoperative follow-up data. Ninety-three limbs in 87 patients were studied. There were 57 male and 30 female patients with an average age of 67.2 years (range: 38-90). We concluded that the combined use of iliac artery angioplasty and infrainguinal surgical revascularization is an effective and durable means of treating multilevel atherosclerotic disease.


Minimal intervention dentistry II: part 4. Minimal intervention techniques of preparation and adhesive restorations. The contribution of the sono-abrasive techniques.
The concept of minimal intervention in oral medicine is based on advances in biological sciences applied to the dental organ. Many cultural barriers, economic as well as technical, have thwarted the application of micro-invasive conservative techniques by the general practitioner. Emerging technologies do not remove all obstacles but promote the integration of less invasive techniques in daily practice. Sono-abrasion is a technique for the selective preparation of enamel and dentine offering excellent efficacy, quality and safety. The authors describe the therapeutic principles, the choice of instrumentation and its mode of action and discuss its interest in adhesive restorative dentistry. The illustrated clinical situations focus on the preservation and optimisation of tissue bonding for both initial lesions and advanced lesions.


Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.
EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.


One gene, multiple ecological strategies: A biofilm regulator is a capacitor for sustainable diversity.
Many bacteria cycle between sessile and motile forms in which they must sense and respond to internal and external signals to coordinate appropriate physiology. Maintaining fitness requires genetic networks that have been honed in variable environments to integrate these signals. The identity of the major regulators and how their control mechanisms evolved remain largely unknown in most organisms. During four different evolution experiments with the opportunist betaproteobacterium Burkholderia cenocepacia in a biofilm model, mutations were most frequently selected in the conserved gene rpfR RpfR uniquely integrates two major signaling systems-quorum sensing and the motile-sessile switch mediated by cyclic-di-GMP-by two domains that sense, respond to, and control the synthesis of the autoinducer cis-2-dodecenoic acid (BDSF). The BDSF response in turn regulates the activity of diguanylate cyclase and phosphodiesterase domains acting on cyclic-di-GMP. Parallel adaptive substitutions evolved in each of these domains to produce unique life history strategies by regulating cyclic-di-GMP levels, global transcriptional responses, biofilm production, and polysaccharide composition. These phenotypes translated into distinct ecology and biofilm structures that enabled mutants to coexist and produce more biomass than expected from their constituents grown alone. This study shows that when bacterial populations are selected in environments challenging the limits of their plasticity, the evolved mutations not only alter genes at the nexus of signaling networks but also reveal the scope of their regulatory functions.


Catalytic asymmetric hydroxylation of oxindoles by molecular oxygen using a phase-transfer catalyst.
The highly enantioselective catalytic hydroxylation of 3-substituted oxindoles was achieved by using a phase-transfer catalyst with molecular oxygen as an oxidant. The product then was converted to an optically active compound 8, which was a synthetic precursor of alkaloid CPC-1.


Oxidation reactions catalyzed by manganese peroxidase isoenzymes from Ceriporiopsis subvermispora.
A total of 11 manganese peroxidase isoenzymes (MnP1-MnP11) with isoelectric points (pIs) in the range of 4.58-3.20 were isolated from liquid- and solid-state cultures of the basidiomycete Ceriporiopsis subvermispora. In the presence of hydrogen peroxide, these isoenzymes showed different requirements for Mn(II) in the oxidation of vanillylacetone, o-dianisidine, p-anisidine and ABTS, whereas oxidation of guaiacol by any isoenzyme did not take place when this metal was omitted. Km values for o-dianisidine and p-anisidine in the absence of Mn(II) are in the range of 0.5-1.0 mM and 4.5-42.0 mM, respectively. Oxalate and citrate, but not tartrate, accelerate the oxidation of o-dianisidine, both in the presence and in the absence of Mn(II). MnPs from this fungus are able to oxidize kojic acid without externally added hydrogen peroxide, indicating that they can also act as oxidases. In this reaction, however, the requirement for Mn(II) is absolute.


Developmental abnormalities and mental retardation: diagnostic strategy.
Intellectual disability formerly called mental retardation (MR) is defined as having an IQ score below 70; the term "developmental delay" (DD) is preferred for young children. A detailed clinical history including a three-generation pedigreee and physical examination are the fundamental steps in achieving an etiological diagnosis in MR. Physical examination should be performed with special emphasis on dysmorphological and neurological exam. Genetic studies have priority in the laboratory investigation of a child with MR. Routine karyotyping is recommended regardless of the degree of MR. Fragile X studies are strongly recommended in both females and males with unexplained MR, especially in patients with a positive family history and typical physical and behavioral features. FISH analysis of subtelomeric regions should be reserved for selected patients. Inborn errors of metabolism are seldom seen as the causes of isolated MR but should be considered in the differential diagnosis of patients with MR/DD in populations where the rate of consanguineous marriages is high. Neuroimaging studies should be performed on an indication basis such as abnormal brain size or neurological findings. It is essential to diagnose the underlying etiology of MR for recognition of treatable disorders, determining prognosis, family counseling, and providing prenatal diagnosis when possible.


High prevalence of neurovascular instability in neurodegenerative dementias.
Orthostatic hypotension and carotid sinus hypersensitivity were assessed in patients meeting clinical criteria for dementia with Lewy bodies (DLB; n=30) and AD (n=35). Cardioinhibitory carotid sinus hypersensitivity (CI) was the most common sign (AD patients, 28%; DLB patients, 41%). Preliminary data from a secondary analysis excluding patients with hypertension or EKG evidence of ischemia suggested that CI may be significantly more common in DLB. Larger studies are needed to evaluate the implications for treatment and to explore the underlying mechanisms.


Gonioscopy-Assisted Transluminal Trabeculotomy Following Failed iStent Surgery.
We describe 4 cases of eyes initially treated with phacoemulsification and iStent trabecular microbypass (Glaukos Corporation). These patients subsequently required further surgery and were successfully treated with the removal of the iStent device followed by gonioscopy-assisted transluminal trabeculotomy (GATT), using the iTrack catheter (Ellex Medical Lasers Ltd). Three of the cases had prior first-generation iStent (G1), and 1 had prior second-generation iStent (G2). This case series demonstrates that in selected cases, a further angle procedure in the form of a GATT can show efficacy and durability in the medium term. Our patients had controlled intraocular pressures (IOPs) at 1-year post-GATT: 2 on IOP-lowering therapy and 2 without any IOP-lowering medications. Three patients had transient hyphema and 2 with high IOP in the immediate postoperative period. No patients experienced a decrease in best-corrected visual acuity postoperatively. To the best of our knowledge, there is no prior literature describing this surgical strategy. This series demonstrates that GATT could potentially be an effective procedure in the case of a failed initial iStent microtrabecular bypass.


Diastereomers of thymidine 3'-O-(methanephosphonothioate): synthesis, absolute configuration and reaction with 3'-methoxyacetylthymidine under conditions of triester approach to oligonucleotide synthesis.
Diastereomers of the title compound were obtained and absolute configuration was assigned by means of stereochemical correlation. Their reaction with 3'-O-methoxyacetylthymidine in the presence of triisopropylbenzenesulphonyl (4-nitro) triazole is neither chemo- nor stereo-selective and leads to diastereomeric pairs of dithymidyl (3',5')methanephosphonate and -methanephosphonothioate. Obtained results are discussed in terms of mechanism of activation of phosphodiesters under conditions known as "phosphotriester approach to oligonucleotide synthesis".


Craniofacial anomalies and mothers' psychological functioning: The mediating role of social support.
To examine the psychological and psychosocial service needs of mothers of children with craniofacial anomalies (CFAs). Mothers (n = 55) of children from newborn to 6 years with CFA completed self-report measures of psychological distress, quality of life and perceived social support. Mothers' psychological distress levels were significantly higher than those in a normative population. Mothers reported lower quality of life than the normative sample. Social support mediated the relationship between quality of life and psychological distress. While most mothers reported a willingness to receive formal psychological support for issues relating to their child's CFA, few had been offered such services. Mothers of children with CFAs may experience increased psychological distress in comparison with the general population. Increased social support may reduce the risk of psychological distress, thus enhancing quality of life among such mothers. The majority of mothers of children with CFAs in Australia may not be routinely offered psychological support services in spite of their elevated psychological risk.


Pre- and/or postsurgical administration of estradiol benzoate increases skin flap viability in female rats.
It has been shown that estrogens have a protective effect with regard to tissue ischemia. Therefore, in this macroscopic and histological investigation, the effect of estradiol benzoate on skin flap viability was studied in sham-operated and ovariectomized Sprague-Dawley rats. Three months prior to flap surgery a group of rats underwent ovariectomy, while the remaining animals underwent a sham operation. Subsequently, all rats had a 2 × 8-cm skin flap created on the dorsum. Rats were randomly divided into estradiol- or saline-treated groups. Treatment started either on the day of flap excision or 3 days prior to the surgery. Our results showed that administration of estradiol benzoate prior to and after flap surgery significantly decreases skin flap necrosis in both sham-operated and ovariectomized rats, with the highest survival rate in animals where treatment started 3 days prior to flap surgery. In conclusion, the observed protective effect of estradiol on skin flap viability could potentially be applied to plastic and reconstructive surgery in postmenopausal women. Nevertheless, further research is needed to explain the exact underlying mechanism and to find the optimal treatment protocol for human clinical practice.


Genetic amniocentesis in seventy twin pregnancies.
Genetic amniocenteses were performed in 70 twin pregnancies over an 11-year period. Both sacs were successfully sampled in 49 of 62 patients (79%). The success rate was decreased (68%) with two placentas (anterior and posterior) and was improved with gestational age greater than or equal to 17 weeks (88%) and with ultrasound visualization of the septum (86%). Of three spontaneous abortions, two were attributed to amniocentesis (chorioamnionitis). When twin pregnancy is diagnosed in a patient with an indication for genetic amniocentesis, a careful reevaluation and discussion of risk factors with the couple are recommended.


Combined standard and novel immunosuppressive substances affect B-lymphocyte function.
A considerable fraction of renal transplanted patients is susceptible to humoral rejection. Today well-established therapy regimens are available to control antibody-mediated rejection in the short term. Nevertheless, donor-specific antibodies persist and graft function deteriorates over time. This might be due to insufficient maintenance immunosuppression - which always consists of two to three drugs with different mechanisms of action. Since T- and B-cell functions always depend on each other in the alloimmune response it is of interest to analyze the effects of combined standard and new immunosuppressive substances with T-cell inhibitory properties on B-cell function. The effectiveness of complementary administrations of sotrastaurin, mycophenolic acid and everolimus on the activation and function of human primary B-lymphocytes was tested. Everolimus and mycophenolic acid alone and in combination proved to be highly effective in suppressing B-cell activation, whereas the proteinkinase C inhibitor sotrastaurin had an unexpected and reverse impact on various B-cell functions when applied in combination with the mammalian target of rapamycin and the inosine monophosphate dehydrogenase inhibitor.


Apolipoprotein C-II synthesis as studied in explants of rat liver in culture.
Adult male Sprague-Dawley rats (200-250 g) were used to study apolipoprotein C-II synthesis and secretion. Liver slices were prepared and incubated in RPMI 1629-medium (tissue amount and incubation time studies) and in Minimum Essential Medium (Eagle) with Earle's salts (hormone experiments). Incubation was performed in scintillation vials in a 95% O2-5% CO2 atmosphere, at 37 degrees C from 1 to 21 hr (2 and 4 hr with hormones). The hormones used and their amounts per millilitre medium were: oestradiol-17 beta 0.1 microgram, progesterone 3.0 micrograms and dexamethasone 1.5 micrograms. Apolipoprotein C-II was determined by specific double immunoprecipitation technique and TCA-insoluble protein fraction represented total protein. Optimal tissue amount was 100 mg/vial and the results show that liver slices quickly secrete the newly synthesized apo C-II (also total protein) into the surrounding medium. There were only minor differences between apo C-II values with the hormones used. The portion of apo C-II synthesis from total protein synthesis was 0.47-1.50%. After 4 hr incubation the [3H]leucine incorporation was almost equal for controls and hormone treated slices.


The biological function of tumor-derived extracellular vesicles on metabolism.
Multiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism. Video Abstract.


Sustained bundle branch reentry in a patient with hypertrophic cardiomyopathy and nondilated left ventricle.
Ventricular tachycardia is a well-known complication in patients with hypertrophic cardiomyopathy. We report the case of a patient with hypertrophic cardiomyopathy with easily inducible monomorphic ventricular tachycardia. Electrophysiology study demonstrated that bundle branch reentry was the mechanism of the tachycardia. The tachycardia was rendered non-inducible by radiofrequency ablation of the right bundle branch.


Up-regulation of ciliary neurotrophic factor receptor expression by GABAA receptors in undifferentiated neural progenitors of fetal mouse brain.
In this study, we evaluated the role of the GABA(A) receptor (GABA(A)R), expressed by undifferentiated neural progenitors isolated from fetal mouse neocortex, in the mechanisms relevant to self-replication and differentiation toward neuronal and astroglial lineages. Round spheres were formed with clusters of proliferating cells within 2-4 days during culture with epidermal growth factor (EGF), whereas the size of these clusters was drastically increased in proportion to increasing durations up to 10 days. Sustained exposure to the GABA(A)R agonist muscimol at 100 microM led to significant increases in the size of neurospheres cultured for 6-10 days, with increased proliferative activity and unchanged lactate dehydrogenase release in a manner sensitive to the GABA(A)R antagonist bicuculline. Muscimol also significantly increased the incorporation of 5-bromo-2'-deoxyuridine in neurospheres in a bicuculline-sensitive manner, whereas both high potassium and nifedipine significantly decreased the neurosphere area with increased numbers of apoptotic cells. Prior activation of GABA(A)R significantly promoted the subsequent expression of an astroglial marker protein in cells differentiated by ciliary neurotrophic factor (CNTF) toward an astroglial lineage after the removal of EGF, with a concomitant decrease in neuronal marker protein expression. In neurospheres with GABA(A)R activation, a significant and predominant increase was seen in mRNA expression of CNTF receptors. These results suggest that prior tonic activation of GABA(A)R may preferentially promote the differentiation by CNTF of neural progenitor cells toward an astroglial lineage through selective up-regulation of CNTF receptor expression in the developing mouse brain.


Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system.
Four different brain regions (parieto-temporal cortex, caudate-putamen, substantia nigra, and thalamus) were examined in rats aged 5, 10, 15, 20, 25, 30, and 35 months. The following enzyme activities related to the antioxidant system were measured: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione peroxidase, glutathione reductase, and superoxide dismutase (as total). Specific enzyme activities vary markedly with age, according to the various regions studied, indicating nonhomogenous vulnerability of different brain regions to aging. In general, both superoxide dismutase and glutathione reductase tended to decline during the last half of life, while glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase tended to increase slightly with age. In rats of 10, 20, or 30 months, chronic treatment for two months with a vasodilator (papaverine) or a calcium-blocker (nicardipine) indicated that the antioxidant enzyme activities are partially influenced according to the exogenous agent used, the brain region tested, and the age of the animals.


Second-Line Chemotherapy in Gastric Cancer: a Retrospective Study.
Second-line chemotherapy is recommended for patients who have disease progression after first-line chemotherapy and have a good performance status. The aim of our study is thus to determine which chemotherapy regimen is more appropriate for second-line gastric cancer treatment. Patients were included if they met the following inclusion criteria: metastatic gastric adenocarcinoma pathology; no previous treatment for local gastric cancer (surgery, chemotherapy, or radiotherapy); received first-line chemotherapy for metastatic gastric cancer and had the disease progress afterward; had adequate organ functions for second-line chemotherapy; had an Eastern Cooperative Oncology Group (ECOG) score 0-2; and were HER-2 negative. The patients were examined in three groups according to the second-line chemotherapy regimen they received. These three groups were compared in terms of overall and progression-free survival. The three groups were statistically similar in overall survival, which was the primary endpoint of the study; the median overall survival was 5 months in the FOLFIRI group (n = 79), 6.5 months in the platinum-based group (n = 55), and 5.6 months in the taxane-based group (n = 40) (p = 0.554). There was no statistical difference between the groups' progression-free survival either; the median progression-free survival time was 3.43 months in the FOLFIRI group, 4 months in the platinum-based group, and 2.77 months in the taxane-based group (p = 0.546). There was no statistically significant difference between the three irinotecan-based, platinum-based, and taxane-based treatments. According to our study's results, the chemotherapy given in second-line treatment should be decided on an individual basis according to toxicity and cost.


Fucoidan from New Zealand Undaria pinnatifida: monthly variations and determination of antioxidant activities.
The content and composition of fucoidans extracted from Undaria pinnatifida from mussel farms at the Marlborough Sounds, New Zealand were investigated using CaCl2 extraction. Crude fucoidan (F0) was subsequently extracted on a monthly basis from U. pinnatifida harvested from July to October 2011 from mussel farms in the Marlborough Sounds, New Zealand. Fucoidan yield varied between the frond and sporophyll parts of the algae, with the sporophyll consistently the highest content. The yield from the sporophyll increased significantly from July (25.4-26.3%) to September (57.3-69.9%). Sulphate content in the extracted fucoidan increased more than twice within the same period, while fucose content remained constant. F0 was further purified by ion-exchange chromatography to yield three fractions, F1, F2 and F3. All three fucoidan fractions contained fucose as the primary sugar component followed by galactose, with xylose, glucose and mannose as minor constituents. All fractions exhibited strong antioxidant activities using the DPPH scavenging and CUPRAC assays. This study showed that sporophyll maturation of U. pinnatifida in New Zealand influenced fucoidan content and composition. Sporophyll fucoidan could potentially be a good resource for natural antioxidants.


Assessment of lemon juice adulteration by targeted screening using LC-UV-MS and untargeted screening using UHPLC-QTOF/MS with machine learning.
The aim of this work was to develop an approach combining LC-MS-based metabolomics and machine learning to distinguish between and predict authentic and adulterated lemon juices. A targeted screening of six major flavonoids was first conducted using ultraviolet ion trap MS. To improve the prediction accuracy, an untargeted methodology was carried out using UHPLC-QTOF/MS. Based on the acquired metabolic profiles, both PCA and PLS-DA were conducted. Results exhibited a cluster pattern and a separation potential between authentic and adulterated samples. Five machine learning models were then developed to further analyze the data. The model of support vector machine achieved the highest prediction power, with accuracy up to 96.7 ± 7.5% for the cross-validation set and 100% for the testing set. In addition, 79 characteristic m/z were tentatively identified. This work demonstrated that untargeted screening coupled with machine learning models can be a powerful tool to facilitate detection of lemon juice adulteration.


Memes and the evolution of religion: We need memetics, too.
In their analysis, Norenzayan et al. completely ignore memetics, which, unlike other theories, treats memes as replicators and looks to memetic as well as genetic advantage. Now that memes are evolving ever faster, genetic advantage is less relevant. So when religious and secular values are at odds, we need a memetic analysis to understand what is going on.


Unusual presentation and treatment of spontaneous celiac artery dissection.
The management options of an isolated celiac artery dissection include medical, open surgical, and endovascular techniques. Which strategy is chosen depends on the severity of the dissection, collateral circulation to the liver, the patient's hemodynamic status, and the surgeon's expertise. We describe an unusual case of celiac artery dissection involving splenic and hepatic arteries complicated by hemorrhage. The patient was successfully treated by coil embolization of the splenic and gastric branches. Hepatic arterial blood flow was preserved with a stent graft extending from the origin of the gastroduodenal artery to the orifice of the celiac artery.


Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner.
Peripheral immune markers have been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, whether dysregulation of peripheral immunity is a risk factor for ALS or a consequence of motor neuron degeneration has not yet been clarified. We aimed to identify longitudinal associations between prediagnostic peripheral immunity and the risk of incident ALS. A total of 345,000 individuals from the UK Biobank between 2006 and 2010 were included at the baseline. The counts of peripheral immune markers (neutrophils, lymphocytes, monocytes, platelets, and CRP) and its derived metrics (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and systemic immune-inflammation index [SII]) were analyzed in relation to the following incident ALS by Cox proportional hazard models. Subgroup and interaction analyses were performed to explore the covariates of these relationships further. After adjusting for all covariates, the multivariate analysis showed that high neutrophil counts and their derived metrics (NLR and SII) were associated with an increased risk of ALS incidence (per SD increment hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.02-1.29 for neutrophils; HR = 1.15, 95% CI = 1.03-1.28 for NLR; and HR = 1.17, 95% CI = 1.05-1.30 for SII). Subgroup and interaction analyses revealed that body mass index (BMI) and age had specific effects on this association. In participants with BMI ≥ 25 or age < 65 years, higher neutrophil counts, and their metrics increased the risk of incident ALS; however, in participants with BMI < 25 or age ≥ 65 years, neutrophils had no effect on incident ALS. Our study provides evidence that increased neutrophil levels and neutrophil-derived metrics (NLR and SII) are associated with an increased risk of developing ALS. ANN NEUROL 2023;94:942-954.


Molecular Mechanisms of Exercise in Brain Disorders: a Focus on the Function of Brain-Derived Neurotrophic Factor-a Narrative Review.
The natural aging process as well as many age-related diseases is associated with impaired metabolic adaptation and declined ability to cope with stress. As major causes of disability and morbidity during the aging process, brain disorders, including psychiatric and neurodegenerative disorders, are likely to increase across the globe in the future decades. This narrative review investigates the link among exercise and brain disorders, aging, and inflammatory biomarkers, along with the function of brain-derived neurotrophic factor. For this study, related manuscript from all databases, Google scholar, Scopus, PubMed, and ISI were assessed. Also, in the search process, the keywords of exercise, neurodegeneration, neurotrophin, mitochondrial dysfunction, and aging were used. Mitochondrial abnormality increases neuronal abnormality and brain disease during the aging process. Stress and inflammatory factors caused by lifestyle and aging also increase brain disorders. Evidences suggest that exercise, as a noninvasive treatment strategy, has antioxidant effects and can reduce neuronal lesions. Brain-derived neurotrophic factor expression following the exercise can reduce brain symptoms; however, careful consideration should be given to a number of factors affecting the results.


Deconfounded and mixed-symmetry versions of the Ponzo illusion figure.
One of the original Ponzo illusion figures, which consists of two converging lines between which two parallel lines of similar length have been inserted orthogonal to the figure's axis of mirror symmetry, was itself mirror-reflected so that the overall shape of the figure became "< >" or "> <", and one line at a time was inserted into each half. The usual illusion - the overestimation of the length of a line that is nearer to a vertex than a farther-away comparison line - occurred. Experiments 1 and 2 used different distances of target and comparison lines to the vertices, but identical distances of these lines from the converging lines, and so, as a tandem, deconfounded the two variables. Experiments 3 and 4 changed the symmetries of the modified Ponzo figure by reducing opposing half-angles of the converging lines or by tilting target and comparison lines concordantly or discordantly. The first measure, which created unequal distances of the endpoints of the target and comparison lines from the converging lines, hardly affected the amount of illusion. The second measure often attenuated the illusion - equally so for concordant and discordant tilts - suggesting that global and local symmetries of the stimuli, and their accordance, were less important than the vertical versus oblique orientation of target and comparison lines. Descriptively, the main cause of the Ponzo illusion seems to be the size of the gap between target and converging lines. The neural substrate of the effect may be interactions between orientation-sensitive and end-inhibited neurons.


Intuitive visualizations of pitch and loudness in speech.
Visualizing acoustic features of speech has proven helpful in speech therapy; however, it is as yet unclear how to create intuitive and fitting visualizations. To better understand the mappings from speech sound aspects to visual space, a large web-based experiment (n = 249) was performed to evaluate spatial parameters that may optimally represent pitch and loudness of speech. To this end, five novel animated visualizations were developed and presented in pairwise comparisons, together with a static visualization. Pitch and loudness of speech were each mapped onto either the vertical (y-axis) or the size (z-axis) dimension, or combined (with size indicating loudness and vertical position indicating pitch height) and visualized as an animation along the horizontal dimension (x-axis) over time. The results indicated that firstly, there is a general preference towards the use of the y-axis for both pitch and loudness, with pitch ranking higher than loudness in terms of fit. Secondly, the data suggest that representing both pitch and loudness combined in a single visualization is preferred over visualization in only one dimension. Finally, the z-axis, although not preferred, was evaluated as corresponding better to loudness than to pitch. This relation between sound and visual space has not been reported previously for speech sounds, and elaborates earlier findings on musical material. In addition to elucidating more general mappings between auditory and visual modalities, the findings provide us with a method of visualizing speech that may be helpful in clinical applications such as computerized speech therapy, or other feedback-based learning paradigms.


Effect of nitrogen, phosphorous, and their interaction on coral reef algal succession in Glover's Reef, Belize.
Nitrogen and phosphorous fertilizers were used to determine their short-term summer effects on algal colonization, abundance, and species composition in moderate herbivory treatments. Secondary succession of algae on coral skeletons was examined in four treatments: an untreated control, a pure phosphate fertilizer, a pure nitrogen fertilizer, and an equal mix of the two fertilizers. Turf algae cover was the only measure of algae abundance to respond significantly to fertilization. Turf cover was three times higher in treatments with added nitrogen when compared with the pure phosphorus treatment. These turfs were dominated by green and cyanobacteria taxa, namely Enteromorpha prolifera, Lyngbya confervoides, and two species of Cladophora. The phosphate treatment was dominated by encrusting corallines and the cyanobacteria L. confervoides, while the controls had the highest cover of frondose brown algae, namely Padina sanctae-crucis and two species of Dictyota. Results indicate that turf algae were co-limited by nitrogen and phosphorus but enrichment appeared to inhibit brown frondose algae that currently dominate these reefs. Number of species was lowest on the pure phosphorus and nitrogen treatments, highest in the controls and intermediate in the mixed treatments, which suggests that diversity is reduced most by an imbalanced nutrient ratio.


Time: the back-door of perception.
Fifty years ago the neurologist MacDonald Critchley observed that parietal cortex damage impaired temporal as well as spatial experience. Whereas the physiological understanding of space has since advanced, the same cannot be said of time. However, in a novel study, recording from single neurons in the macaque, Leon and Shadlen show that a region of the parietal cortex appears to encode time. The area in which these neurons reside also contains spatially selective neurons and overlaps with the area recently reported to contain number neurons.


Anesthetic considerations for high order cesarean sections: a prospective cohort study.
In a previous retrospective study we demonstrated that perioperative complications occurred in a minority of high order repeat cesarean sections (HOR-C/S). In this prospective study we compared the incidence of complications in patients who have had four or more cesarean sections to those that had three or less. This was a prospective, observational cohort study of parturients undergoing C/S at a single tertiary care hospital over a 1 year period. We compared the incidence of conversion from regional to general anesthesia, duration of surgery and incidence of major blood loss in HOR-C/S to control. We studied a total of 831 parturients, 129 underwent HOR-C/S. The incidence of conversion from regional to general anesthesia was similar in both groups (RR = 0.97, 95% CI 0.2, 4.3). The median duration of surgery was 40 min (range 10-145 min) in the HOR-C/S group and 30 min (range 10-150 min) in the control group (p < 0.001). The incidence of prolonged surgery was increased in the HOR-C/S group (RR = 3.6, 95% CI 2.4, 5.4). The incidence of intraoperative blood transfusion was higher in the HOR-C/S group (RR = 3.4, 95% CI 1.1, 10.2). Patients who have HOR-C/S are more likely to have prolonged surgery and require blood transfusion than controls. However, in our population, this was not associated with an increased incidence of conversion from regional to general anesthesia. Provided causes of severe hemorrhage such as abnormal placentation have been ruled out, HOR-C/S is not an absolute contraindication to regional block.


Thallium exposure induces changes in B and T cell generation in mice.
Thallium (Tl) is a high-priority toxic metal that poses a severe threat to human health. The toxicity characteristics induced by Tl have been partially discussed. However, the immunotoxic effects of Tl exposure have remained largely unexplored. Our findings demonstrated that 50 ppm of Tl exposure for one week induced severe weight loss in mice, which was accompanied by appetite suppression. Moreover, although Tl exposure did not induce significant pathological damage to skeletal muscle and bone, Tl inhibited the expression of B cell development-related genes in the bone marrow. Additionally, Tl exposure increased B cell apoptosis and reduced its generation in the bone marrow. Analysis of B cells in the blood indicated that the percentage of B-2 cells decreased significantly, whereas B-2 cell proportions in the spleen did not. The percentage of CD4+ T cells in the thymus increased significantly, and the proportion of CD8+ T cells did not. Furthermore, although the proportion of the total CD4+ and CD8+ T cells was not significantly altered in the blood and spleen, Tl exposure promoted the migration of naïve CD4+ T cells and recent thymic emigrants (RTEs) from the thymus to the spleen. These results suggest that Tl exposure can affect B and T cell generation and migration, which provides new evidence for Tl-induced immunotoxicity.


[Effect of xinmaitong capsule on damage of lipid peroxidation in coronary heart disease patients with myocardial ischemia].
To assess the effect of Xinmaitong Capsule (XMTC) in treating coronary heart disease(CHD). The superoxide dismutase(SOD) and malonyldialdehyde(MDA) levels, ST of electrocardiogram and clinical symptoms of 25 CHD patients with myocardial ischemia were observed before and after treatment with XMTC and 15 patients with Composite Danshen Tablet (CDT) were studied as controls. The SOD level was significantly lower than that of normal (P < 0.001), and MDA significantly increased (P < 0.001). After treatment with XMTC, the SOD levels and ST of ECG were significantly increased (P < 0.001). In the control group, the SOD levels and ST of ECG were unchanged (P > 0.05), MDA and scores of clinical symptoms were decreased (P < 0.05, P < 0.001), but the levels of them were markedly higher than those in the XMTC group (P < 0.01). Lipid peroxidation injury is closely related with the myocardial ischemia and Syndrome Differentiation of TCM, XMTC with function of supplementing Qi and activating blood circulation could resist lipid peroxidation injury.


The variance of the index (R) of aggregation of Clark and Evans.
The exact formula for the variance of the Index (R) of aggregation of Clark and Evans is derived. Due to the fact that R is a dimensionless number, its variance is independent of population density, being only a function of the sample size and so can be manipulated.


Association of reduced zinc status with poor glycemic control in individuals with type 2 diabetes mellitus.
This study evaluated the relationship between the zinc-related nutritional status and glycemic and insulinemic markers in individuals with type 2 diabetes mellitus (T2DM). A total of 82 individuals with T2DM aged between 29 and 59 years were evaluated. The concentration of zinc in the plasma, erythrocytes, and urine was determined by the flame atomic absorption spectrometry method. Dietary intake was assessed using a 3-day 24-h recall. In addition, concentrations of serum glucose, glycated hemoglobin percentage, total cholesterol and fractions, triglycerides, and serum insulin were determined. The insulin resistance index (HOMA-IR) and β-cell function (HOMA- β) were calculated. The markers of zinc status (plasma: 83.3±11.9μg/dL, erythrocytes: 30.1±4.6μg/g Hb, urine: 899.1±622.4μg Zn/24h, and dietary: 9.9±0.8mg/day) were classified in tertiles and compared to insulinemic and glycemic markers. The results showed that lower zinc concentrations in plasma and erythrocytes, as well as its high urinary excretion, were associated with higher percentages of glycated hemoglobin, reflecting a worse glycemic control in individuals with T2DM (p<0.05). Furthermore, there was a significant inverse correlation between plasma zinc levels and glycated hemoglobin percentage (r=-0.325, p=0.003), and a positive correlation between urinary zinc excretion and glycemia (r=0.269, p=0.016), glycated hemoglobin percentage (r=0.318, p=0.004) and HOMA-IR (r=0.289, p=0.009). According to our study results, conclude that T2DM individuals with reduced zinc status exhibited poor glycemic control.


Association Between Endothelial Progenitor Cells and Treatment Response in Non-Squamous Non-small Cell Lung Cancer Treated with Bevacizumab.
To investigate the association between the number of circulating endothelial progenitor cells (EPCs) in non-squamous non-small cell lung cancer (NSCLC) and disease outcome, in combination chemotherapy with and without bevacizumab. We retrospectively identified 25 non-squamous NSCLC cases, and divided them into high-EPC and low-EPC groups. Within each group, we compared disease outcomes, with or without the administration of bevacizumab. In the high-EPC group, chemotherapy with bevacizumab produced a significantly higher tumor reduction rate and objective response rate, with significantly longer progression-free survival, compared to chemotherapy without bevacizumab (p<0.001, p=0.010, and p<0.001, respectively). However, in the low-EPC group, there were no significant differences in disease outcomes in groups with versus those without bevacizumab. The number of EPCs may be a useful biomarker to guide decision-making in the use of bevacizumab in non-squamous NSCLC.


Differential expression of Rous Sarcoma virus-specific transformation parameters in enucleated cells.
Chicken embryo fibroblasts transformed with the Ta and ts68 mutants of Rous Sarcoma virus (RSV) were enucleated and studied for their capacity to express reversibly the transformed phenotype in response to temperature changes. After shift to the permissive temperature (35 degrees C), the cytoplasts acquired a transformed morphology and displayed characteristic ruffles and microvilli at their surface. As detected by immunofluorescence, they also lost their actin filament cables and exhibited characteristic changes in the pattern of cell surface structures containing LETS protein. Expression of all these transformation parameters was reversible after shiftback to the nonpermissive temperature (41 degrees C). These results indicate that a whole set of changes characteristic for the transformed phenotype can be expressed independently of the cell nucleus. In contrast, ts mutant-infected cytoplasts were no longer able to respond to temperature shifts with changes in their hexose transport rate. Cytoplasts prepared from cells grown at 41 degrees C retained their low rate of hexose uptake after shift to 35 degrees C, whereas cytoplasts from cells grown at 35 degrees C exhibited a high rate of hexose transport even after 10 hr of shift to 41 degrees C. These results are in accordance with the hypothesis that the product of the src gene of RSV represents a multifunctional protein which acts independently on nuclear and extranuclear sites.


β-carotene regulates cancer stemness in colon cancer in vivo and in vitro.
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. CD133+CD44+ HCT116 and CD133+CD44+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133+CD44+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133+CD44+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.


[Effect of clarithromycin treatment of natural killer cell activity in patients with advanced non-small cell lung cancer].
The treatment of a 14-membered ring macrolide, clarithromycin (CAM), prolongs the survival time of patients with unresectable nonsmall cell lung cancer, and improves the host factor. As we previously reported, one of the underlying mechanisms is that the treatment of CAM increases the bioactivity of interleukin-12 (IL-12). In the present study, we administered CAM to murine lung cancer treatment models with Lewis lung carcinoma and to 18 patients with unresectable non-small lung cancer whose anticancer treatment had been terminated. The timing of CAM administration was examined and the time course of NK activity was measured. In the murine lung cancer treatment models, administration of CAM 7 days after anticancer chemotherapy more strongly inhibited the tumor growth and more rapidly and significantly increased NK activity, compared to the concomitant use of CAM with an anticancer chemotherapy. In humans, the NK activity which had decreased after anticancer treatment, tended to be increased after one month of treatment with CAM (p = 0.06). One month of treatment with CAM significantly increased the NK activity (p < 0.05) of the following subjects: patients with stage III in the clinical stages, patients with squamous cell carcinoma, patients who had received radiotherapy alone as pretreatment therapy, and patients whose pretreatment therapy effect was partial response (PR). We conjectured that increasing NK activity was one of the underlying mechanisms of the macrobiotic effect of CAM. CAM was especially effective for patients in the early clinical stages and patients who responded well to pretreatment therapy. Murine lung cancer models showed that non-concomitant use of CAM with anticancer chemotherapy was more effective.


Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells.
To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-buthionine-SR-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in approx. 95% depletion of GSH in the cells. The depletion of GSH did not influence the rate of cell growth, the amount of cell protein or the chromosome structure during culture for at least 24 h. Cells depleted or not depleted of GSH were challenged with (1-5).10(-5) M CdCl2 for 2 h and subsequent cell growth was evaluated. The cytotoxicity of cadmium was enhanced with increasing duration of BSO pretreatment and was correlated with the decrease of cell GSH, indicating that GSH constitutes a cellular defense against toxicity by cadmium. Inducibility of MTs by zinc was investigated in cultured V79 cells. Incubation of the cells with 1.10(-4) M zinc acetate did not result in accumulation of MTs over the control values for up to 2 h. Thereafter, however, the synthesis of MTs increased with increasing duration of zinc treatment and an approx. 9-fold increase in the amount of MTs was observed 10 h after addition of zinc. Depletion of cell GSH by BSO did not much influence the increased accumulation of MTs by zinc. In contrast, zinc at the same concentration did not influence the level of cell glutathione up to 12 h. The cytotoxicity of cadmium was markedly reduced in the cells pretreated with zinc and the protective effect of zinc was dependent upon duration of pretreatment, being parallel with the increased accumulation of MTs. Protection of cells from cadmium toxicity by zinc pretreatment was as or a little more effective in the cells depleted of GSH as in those not depleted. Thus, glutathione appears to be an intrinsic protector against cadmium toxicity, while MTs serve as an induced cellular defense that is mobilized against heavy metal stress, but takes more than 2 h to accumulate in significant amounts. Accordingly, it is suggested that GSH and MTs have cooperative protective roles against cadmium toxicity, as an initial defense for the former and a second-stage defense for the latter.


Noradrenaline reversal in canine subcutaneous adipose tissue.
Although adrenaline reversal is a well known phenomenon, fewer investigations have demonstrated reversal of the vascular response to noradrenaline (NA). The present studies compared subcutaneous adipose tissue vascular responses to intra-arterial NA with those of sympathetic nerve stimulation. Both NA and electrical stimulation produced vasoconstriction in adipose tissue which was reversed to beta-adrenergically mediated vasodilation following local alpha-adrenergic block.


Evaluation of bacterial growth inhibition by mercaptopropionic acid in metallo-β-lactamase detection on multidrug-resistant Acinetobacter baumannii.
Metallo-β-lactamase (MBL) has been reported all over the world. The inhibitory effect of mercaptopropionic acid (MPA) on bacterial growth was evaluated by comparison between disk diffusion and broth dilution methodology with determination of the minimum inhibitory concentration (MIC) for multidrug-resistant Acinetobacter baumanni strains. MPA significantly inhibited growth of the strains. The use of MPA can affect the results in phenotypic methods of MBL detection.


Population pharmacokinetic analysis of rebamipide in healthy Korean subjects with the characterization of atypical complex absorption kinetics.
In this study, the population pharmacokinetic (PK) analysis of rebamipide (Reba) in healthy male Korean subjects was analyzed using the nonlinear mixed effects modeling method. The possible effects of physiological covariates and the multidrug resistance (MDR1) gene 3435C>T polymorphism on PK parameters were also investigated. Data were collected from a bioequivalence study, in which 26 subjects who participated in the study were administered a single oral dose of 100 mg Reba; only data from the reference formulation were used. Reba showed a relatively large inter-individual variability (from 2.6- to 3.3-fold) in the PK parameters with double peaks or the concentration plateau after the peak concentration in its serum concentration-time profiles. The population PKs of Reba was best described by a one-compartment model with three fraction absorption processes followed a single Weibull-type function and two first-order kinetics, and lag times. The study suggests that the efflux transporter MDR1 3435C>T allele affects the substantial inter-individual variability in the absorption of Reba according to genetic polymorphism. A significant difference was found in the absorption rate ka 1 among the MDR1 3435C>T genotype groups (P < 0.05) (CT group, 79.8% increase; and TT group, 115% increase). The use of combined MDR1 3435C>T and body mass index as covariates for ka 1 exerted a more significant effect (P < 0.05). In addition, body surface area significantly affected the apparent total clearance (P < 0.05).


Genetic Factors Contribute to Risk for Neonatal Respiratory Distress Syndrome among Moderately Preterm, Late Preterm, and Term Infants.
To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African- and European-descent. We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n = 225) and compared the concordance of RDS between monozygotic and dizygotic twins. Using mixed-effects logistic regression, we identified covariates that increased disease risk. We performed additive genetic, common environmental, and residual effects modeling to estimate genetic variance and used the ratio of genetic variance to total variance to estimate genetic contribution to RDS disease risk. Monozygotic twins were more concordant for RDS than dizygotic twins (P = .0040). Estimated gestational age, European-descent, male sex, delivery by cesarean, and 5-minute Apgar score each independently increased risk for RDS. After adjusting for these covariates, genetic effects accounted for 58% (P = .0002) of the RDS disease risk variance for all twin pairs. In addition to environmental factors, genetic factors may contribute to RDS risk among moderately preterm, late preterm, and term infants. Discovery of risk alleles may be important for prediction and management of RDS risk.


Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats.
We have recently shown that chronic THC administration in adolescent female rats induces subtle but lasting alterations in the emotional circuit ending in depressive-like behaviour at adulthood. Here we describe other relevant depressive-like symptoms present in these animals. Adult female rats pretreated with THC display passive coping strategy towards acute stressful situations as demonstrated by their behaviours in the first session of the forced swim test, develop a profound anhedonic state as demonstrated by the reduced consumption of palatable food and present a decrease in social functioning. Besides the emotional symptoms, adolescent exposure to THC induced a significant deficit in object recognition memory. Since it has been reported that deficits in adult hippocampal neurogenesis may underlie the cognitive dysfunction seen in depression, we then survey cell proliferation in the dentate gyrus of the hippocampus. Adolescent THC exposure significantly reduced the number of BrdU-positive cells in THC-treated rats as well as hippocampal volume. We suggest that this complex depressive-like phenotype is triggered by a long-lasting decrease in CB1 receptor functionality in specific brain regions. To test whether an increase in the endocannabinoid signalling could ameliorate the depressive phenotype, adult female rats pre-exposed to THC were injected with URB597 (0.3mg/kg ip) and then tested in behavioural assays. URB597 was able to reverse most depressive-like symptoms induced by adolescent THC exposure such as the passive coping strategy observed in THC exposed animals in the forced swim test as well as anhedonia and the reduced social activity. These results support a role for the endocannabinoid system in the neurobiology of depression and suggest the use of URB597 as a new therapeutic tool with antidepressant properties.


Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study.
1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pmoles) and systemic (1 mg kg(-1), i.v.) administrations of 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a selective I-imidazoline receptor ligand, increased the firing rate of LC cells (maximal increase: 22+/-5%, P<0.001 and 16+/-7%, P<0.001 respectively). Chronic pretreatment with the irreversible monoamine oxidase inhibitor clorgyline (3 mg kg(-1), i.p., every 12 h for 14 days) abolished this effect. 3. In rat midpontine brain slices containing the LC, bath application (1 mM) of the imidazolines 2-BFI, 2-(4,5-dihydroimidaz-2-yl)-quinoline (BU224), idazoxan, efaroxan, phentolamine and (2-2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline (RX821002) reversibly stimulated LC cells. The maximal effect was approximately 90% except for RX821002 and efaroxan which induced smaller maximal effects (approximately 58% and approximately 35% respectively). Simultaneous application of idazoxan and 2BFI did not lead to additive effects. 4. Bath application of the alpha2-adrenoceptor antagonists, yohimbine (1 - 10 microM) and N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) (10 microM), failed to modify LC activity. The irreversible blockade of alpha2-adrenoceptors with EEDQ (10 microM) did not alter the effect of idazoxan or that of efaroxan. Previous application of clorgyline (10 microM) did not modify the excitatory effect of 2-BFI or efaroxan. 5. Changes in the pH of the bathing solution (6.84-7.84) did not influence the effect caused by idazoxan. Bath application of 2-BFI (1 mM) reversed the inhibition induced by diazoxide (300 microM), an ATP-sensitive K+ channel opener, whereas application of glibenclamide (3 microM), an ATP-sensitive K+ channel blocker, partially blocked the effect of 2-BFI. 6. This study shows that imidazoline compounds stimulate the firing rate of LC neurons. This effect is not mediated by alpha2-adrenoceptors nor by I1 or I2-imidazoline receptors but involves a different subtype of imidazoline receptor. Our results indicate that this receptor is located extracellularly and modulates ATP-sensitive K+ channels.


CD8+ T cells and immunoregulatory networks in asthma.
It is well established that infection with respiratory viruses can cause acute local inflammation in humans and is a leading cause in the hospitalization of asthmatics. Less well recognized is the potential for viral infections to actually protect against the development of asthma, as are the cellular mechanisms which might underlie such protection. This review outlines the basic immunological pathways involved in atopic asthma and details the currently recognized cellular mechanisms induced by respiratory viral infections which can protect against the development of asthma. Specifically, it appears that virus infection induced memory T cells that remain in tissues, e.g. the lung and airways, can under certain circumstances create a local cytokine milieu which inhibits the development of ensuing allergic immune responses at that site. One key aspect of this immune modulation is the cytokine-dependent communication which occurs between the innate and the adaptive immune systems. The mechanistic principles underlying this form of immunomodulation should be taken into consideration when developing future forms of therapy and rational vaccine design.


Renal function in patients with high serum fluoride concentrations after prolonged sevoflurane anesthesia.
In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia. Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group. The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups. The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.


Effects of temperature and particle concentration on aggregation of nanoplastics in freshwater and seawater.
Microplastics have become a significant environmental problem worldwide. Compared with microplastics, nanoplastics are apparently more abundant and harmful but their environmental processes are less well understood. The fate and ecological impacts of nanoplastics in aquatic environments are largely determined by their aggregation properties, which were investigated here using pure water and artificial seawater prepared in the laboratory, as well as river water and coastal seawater collected from subtropical Hong Kong. The tests were carried out at an environmentally realistic temperature range (15-35 °C) with particle concentrations over four orders of magnitude (0.1-100 mg L-1). Under these experimental conditions, parameters of dynamic light scattering were used to determine the extent of aggregation and colloidal stability of polystyrene nanospheres (nPS), a common test model of nanoplastics. Our results showed that aggregation of nPS was minimal in pure water and river water, but became strong under the ionic strength of artificial seawater and coastal seawater, in which 70 nm nPS could aggregate to > 2000 nm, and this aggregation clearly increased with increase in temperature and particle concentration. The aggregates with increasing size and decreasing colloidal stability were deposited more quickly. Findings from this study imply an increased risk of nanoplastics to marine benthic organisms through the aggregation and deposition processes, particularly in warmer waters.


The double agents in liquid biopsy: promoter and informant biomarkers of early metastases in breast cancer.
Breast cancer continues to be a major global problem with significant mortality associated with advanced stage and metastases at clinical presentation. However, several findings suggest that metastasis is indeed an early occurrence. The standard diagnostic techniques such as invasive core needle biopsy, serological protein marker assays, and non-invasive radiological imaging do not provide information about the presence and molecular profile of small fractions of early metastatic tumor cells which are prematurely dispersed in the circulatory system. These circulating tumor cells (CTCs) diverge from the primary tumors as clusters with a defined secretome comprised of circulating cell-free nucleic acids and small microRNAs (miRNAs). These circulatory biomarkers provide a blueprint of the mutational profile of the tumor burden and tumor associated alterations in the molecular signaling pathways involved in oncogenesis. Amidst the multitude of circulatory biomarkers, miRNAs serve as relatively stable and precise biomarkers in the blood for the early detection of CTCs, and promote step-wise disease progression by executing paracrine signaling that transforms the microenvironment to guide the metastatic CTCs to anchor at a conducive new organ. Random sampling of easily accessible patient blood or its serum/plasma derivatives and other bodily fluids collectively known as liquid biopsy (LB), forms an efficient alternative to tissue biopsies. In this review, we discuss in detail the divergence of early metastases as CTCs and the involvement of miRNAs as detectable blood-based diagnostic biomarkers that warrant a timely screening of cancer, serial monitoring of therapeutic response, and the dynamic molecular adaptations induced by miRNAs on CTCs in guiding primary and second-line systemic therapy.


A systematic review of long-term complications of mechanical tubal occlusion.
To collate the available evidence of the rare but identified late complications of mechanical tubal occlusion. The primary objective is to describe the nature of these longer-term acute presentations. Secondary objectives are: 1) to delineate their aetiology, 2) characterise imaging findings and 3) identify successful management options. Literature search using National Institute of Clinical Excellence Healthcare Databases Advanced Search and terms (complicat* OR torsion OR infect* OR migrat* OR extru*) AND (tubal occlusion OR sterili*). Results reviewed by CM and JH for eligibility. 33 published case reports of long-term complications of mechanical tubal occlusion. 30 demonstrated migration of the device. 16 had infective pathology. Multiple modalities of imaging used with no clear evidence that one was superior. Medical and surgical management was used with removal of device proving definitive treatment. Long-term complications of mechanical tubal occlusion are rare and show a varied clinical course. Clinicians should be mindful of this when evaluating patients in the acute setting, as there is no identified timeline as to when complications may occur. Imaging is almost always essential for diagnosis and the modality should be directed by the clinical presentation. Definitive management is by removal of the occlusive device, but this carries its own risks.


Comparison of artesunate and quinine in the treatment of Sudanese children with severe Plasmodium falciparum malaria.
Sixty-six children presenting to Singa hospital, Sudan with different manifestations of severe Plasmodium falciparum malaria were randomly divided into two well-matched groups (33 in each arm) to receive either intravenous artesunate 2·4 mg/kg at 0, 12, and 24 hours, then daily, or intravenous quinine 20mg/kg initially then 10mg/kg three times a day. There was no significant difference in the fever, parasite clearance, and coma resolution times. Three patients died, one in the artesunate and two in the quinine groups. One patient developed hypoglycaemia following quinine infusion. Thus, artesunate can be used for the treatment of severe falciparum malaria.


X-ray structure of Clostridium perfringens sortase B cysteine transpeptidase.
The pathogenesis and infectivity of Gram-positive bacteria are mediated by many surface proteins that are covalently attached to peptidoglycans of the cell wall. The covalent attachment of these proteins is catalyzed by sortases (Srts), a family of cysteine transpeptidases, which are classified into six classes, A - F, based on their amino acid sequences and biological roles. Clostridium perfringens, one of the pathogenic clostridial species, has a class B sortase (CpSrtB) with 249 amino acid residues. X-ray structures of CpSrtB and its inactive mutant form were determined at 2.2 Å and 1.8 Å resolutions, respectively. CpSrtB adopts a typical sortase-protein fold, and has a unique substrate-binding groove formed by three β-strands and two helices creating the sidewalls of the groove. The position of the catalytic Cys232 of CpSrtB is significantly different from those commonly found in Srts structures. The modeling study of the CpSrtB/peptide complex suggested that the position of Cys232 found in CpSrtB is preferable for the catalytic reaction to occur. Structural comparison with other class B sortases demonstrated that the catalytic site likely converts between two forms. The movement of Cys232 between the two forms may help His136 deprotonate Cys232 to be activated as a thiolate, which may the catalytic Cys-activated mechanism for Srts.


Erythrocyte folate content and serum folic acid and homocysteine levels in preeclamptic primigravidae teenagers living at high altitude.
To measure erythrocyte folate content and serum folic acid and homocysteine (Hcy) levels in preeclamptic primigravidae teenagers living at high altitude. Measured analytes were compared to those found in normal teen controls. Teenagers complicated with preeclampsia displayed significantly lower hematocrit and erythrocyte folic acid levels with higher serum Hcy levels as compared to controls (36.40 ± 4.90 vs. 38.99 ± 2.89 %, 493.80 ± 237.30 vs. 589.90 ± 210.60 ng/mL, and 7.29 ± 2.52 vs. 5.97 ± 1.41 μmol/L, respectively, p < 0.05). There was a non-significant trend for lower serum folic acid levels among preeclampsia teenagers. Serum and erythrocyte folic acid levels positively correlated in preeclampsia teenagers, and levels of both analytes inversely correlated with Hcy levels. This pilot study found that teenagers complicated with preeclampsia living at higher altitude displayed lower erythrocyte folate content in addition to higher serum Hcy levels. More research is warranted to determine the clinical implications of these findings.


Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance.
Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom(®) SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms.


Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox.
1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120-150 min after administration of 500 mg of the antilipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus. 2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 +/- 0.02 versus 0.55 +/- 0.05 mmol/l, P less than 0.001) and blood glycerol (8 +/- 1 versus 56 +/- 8 mumol/l, P less than 0.001) concentrations. The lipid oxidation rate was decreased (0.63 +/- 0.05 versus 1.02 +/- 0.08 mg min-1 kg-1, P less than 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 +/- 0.17 versus 1.22 +/- 0.18 mg min-1 kg-1, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)