Determinants of pulmonary perfusion measured by electrical impedance tomography.
Electrical impedance tomography (EIT) is a non-invasive imaging technique for detecting blood volume changes that can visualize pulmonary perfusion. The two studies reported here tested the hypothesis that the size of the pulmonary microvascular bed, rather than stroke volume (SV), determines the EIT signal. In the first study, the impedance changes relating to the maximal pulmonary pulsatile blood volume during systole (Delta Z(sys)) were measured in ten healthy subjects, ten patients diagnosed with chronic obstructive pulmonary disease, who were considered to have a reduced pulmonary vascular bed, and ten heart failure patients with an assumed low cardiac output but with a normal lung parenchyma. Mean Delta Z(sys) (SD) in these groups was 261 (34)x10(-5), 196 (39)x10(-5) ( P<0.001) and 233 (61)x10(-5) arbitrary units (AU) (P=NS), respectively. In the second study, including seven healthy volunteers, Delta Z(sys) was measured at rest and during exercise on a recumbent bicycle while SV was measured by means of magnetic resonance imaging. The Delta Z(sys) at rest was 352 (53)x10(-5 ) and 345 (112)x10(-5 )AU during exercise (P=NS), whereas SV increased from 83 (21) to 105 (34) ml (P<0.05). The EIT signal likely reflects the size of the pulmonary microvascular bed, since neither a low cardiac output nor a change in SV of the heart appear to influence EIT.


The effect of dipeptidyl peptidase-4 inhibition on gastric volume, satiation and enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled crossover study.
The incretin hormone glucagon-like peptide-1 (GLP-1) retards gastric emptying and decreases caloric intake. It is unclear whether increased GLP-1 concentrations achieved by inhibition of the inactivating enzyme dipeptidyl peptidase-4 (DPP-4) alter gastric volumes and satiation in people with type 2 diabetes. In a double-blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50 mg bid) or placebo for 10 days in random order separated by a 2-week washout. On day 7, fasting and postmeal gastric volumes were measured by a (99m)Tc single-photon emission computed tomography (SPECT) method. On day 8, a liquid Ensure meal was consumed at 30 ml/min, and maximum tolerated volume (MTV) and symptoms 30 min later were measured using a visual analogue scale (VAS) to assess effects on satiation. On day 10, subjects ingested water until maximum satiation was achieved. The volume ingested was recorded and symptoms similarly measured using a VAS. Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 +/- 21 vs. 247 +/- 19 ml, P = 0.98) and fed (746 +/- 28 vs. 772 +/- 26 ml, P = 0.54) gastric volumes did not differ when subjects received vildagliptin or placebo. Treatment with vildagliptin did not alter the MTV of Ensure (1657 +/- 308 vs. 1389 +/- 197 ml, P = 0.15) or water compared to placebo (1371 +/- 141 vs. 1172 +/- 156 ml, P = 0.23). Vildagliptin was associated with decreased peptide YY (PYY) concentrations 60 min after initiation of the meal (166 +/- 27 vs. 229 +/- 34 pmol/l, P = 0.01). Vildagliptin does not alter satiation or gastric volume in people with type 2 diabetes despite elevated GLP-1 concentrations. Compensatory changes in enteroendocrine secretion could account for the lack of gastrointestinal symptoms.


Postscription: The Compounding Pharmacy in Brazil: A Pharmacist's Perspective.
This is the first of a series of articles from compounders from around the world who explain their perspective on compounding pharmacy within their country. In this article, the authors have provided a brief synopsis of compounding pharmacy in Brazil.


Electrical response of bat retina to spectral stimulation: comparison of four microhiropteran species.
Electrical responses of the retinas of 4 species of microchiropteran bats stimulated by spectrally restricted light flashes were found to diverge systematically from the rhodopsin absorption spectrum. The divergence was progressively greater across the 4 species. The results appeared explainable by assuming a second photoreceptor class and photopigment which was present in progressively greater numbers in the retinas of Eptesicus fuscus, Desmodus rotundus, Artibeus jamaicensis and Carollia perspicillata.


Trypan blue capsule staining to visualize the capsulorhexis in cataract surgery.
A capsulorhexis may be difficult to perform in the absence of a red fundus reflex. Using 0.1 mL of trypan blue 0.1% to stain the anterior capsule in 30 patients with a mature cataract enabled us to visualize the capsulorhexis during phacoemulsification. No adverse reactions were observed up to 12 months after surgery. Trypan blue staining of the anterior capsule appears to be a safe technique to facilitate the performance of a capsulorhexis in the absence of a red fundus reflex.


Antimicrobial peptide P18 inhibits inflammatory responses by LPS- but not by IFN-gamma-stimulated macrophages.
Antimicrobial peptide P18 markedly inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, whereas magainin 2 did not inhibit these activities. P18 dose-dependently reduced nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophage cells, with complete inhibition at 20 microg P18 ml(-1). In contrast, P18 had no effect on NO production and the expression of iNOS mRNA and iNOS protein by interferon-gamma (IFN-gamma)-stimulated RAW264.7 cells, suggesting P18 selectively inhibits LPS-stimulated inflammatory responses in macrophages. An LAL assay showed that P18 has strong LPS-neutralizing activity, indicating that P18 inhibits the inflammatory responses in LPS-stimulated macrophages by direct binding to LPS. Collectively, our results indicate that P18 has promising therapeutic potential as a novel anti-inflammatory as well as antimicrobial agent.


Deciphering "the language of nature": A transformer-based language model for deleterious mutations in proteins.
Various machine-learning models, including deep neural network models, have already been developed to predict deleteriousness of missense (non-synonymous) mutations. Potential improvements to the current state of the art, however, may still benefit from a fresh look at the biological problem using more sophisticated self-adaptive machine-learning approaches. Recent advances in the field of natural language processing show that transformer models-a type of deep neural network-to be particularly powerful at modeling sequence information with context dependence. In this study, we introduce MutFormer, a transformer-based model for the prediction of deleterious missense mutations, which uses reference and mutated protein sequences from the human genome as the primary features. MutFormer takes advantage of a combination of self-attention layers and convolutional layers to learn both long-range and short-range dependencies between amino acid mutations in a protein sequence. We first pre-trained MutFormer on reference protein sequences and mutated protein sequences resulting from common genetic variants observed in human populations. We next examined different fine-tuning methods to successfully apply the model to deleteriousness prediction of missense mutations. Finally, we evaluated MutFormer's performance on multiple testing datasets. We found that MutFormer showed similar or improved performance over a variety of existing tools, including those that used conventional machine-learning approaches. In conclusion, MutFormer considers sequence features that are not explored in previous studies and can complement existing computational predictions or empirically generated functional scores to improve our understanding of disease variants.


Longitudinal study of 2 patients with cyclic thrombocytopenia, STAT3 and MPL mutations.
Cyclic thrombocytopenia (CTP) is a rare disease of periodic platelet count oscillations. The pathogenesis of CTP remains elusive. To study the underlying pathophysiology and genetic and cellular associations with CTP, we applied systems biology approaches to 2 patients with stable platelet cycling and reciprocal thrombopoietin (TPO) cycling at multiple time points through 2 cycles. Blood transcriptome analysis revealed cycling of platelet-specific genes, which are in parallel with and precede platelet count oscillation, indicating that cyclical platelet production leads platelet count cycling in both patients. Additionally, neutrophil and erythrocyte-specific genes also showed fluctuations correlating with platelet count changes, consistent with TPO effects on hematopoietic progenitors. Moreover, we found novel genetic associations with CTP. One patient had a novel germline heterozygous loss-of-function (LOF) thrombopoietin receptor (MPL) c.1210G>A mutation, and both had pathogenic somatic gain-of-function (GOF) variants in signal transducer and activator of transcription 3 (STAT3). In addition, both patients had clonal T-cell populations that remained stable throughout platelet count cycles. These mutations and clonal T cells may potentially involve in the pathogenic baseline in these patients, rendering exaggerated persistent thrombopoiesis oscillations of their intrinsic rhythm upon homeostatic perturbations. This work provides new insights into the pathophysiology of CTP and possible therapies.


Fitting of 2D WAXD data: Mesophases in polymer fibers.
This data article presents fitting results of wide-angle x-ray diffraction (WAXD) patterns of melt-spun polymer fibers from amorphous materials (polycarbonate (PC), cyclo-olefin polymer (COP), copolyamide (coPA), polyethylene terephthalate glycol (PETG)) and semi-crystalline materials (polyethylene terephthalate (PET), poly-3-hydroxybutyrate(P3HB)). The data was fit using the fitting algorithms, previously described in the publication by Perret and Hufenus 'Insights into strain-induced solid mesophases in melt-spun polymer fibers' [1]. Fitting results of WAXD data and details about azimuthal, equatorial, meridional or off-axis profiles are presented in sections 1.1-1.2. SAXS patterns of fibers, melt-spun from amorphous materials, are shown in section 1.3. Fiber production parameters are given in section 2.1, and a description of the WAXD measurements and fitting details, e.g., the chosen fitting parameters, are given in section 2.2.


Recent progress of self-immobilizing and self-precipitating molecular fluorescent probes for higher-spatial-resolution imaging.
Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells and tissues and may play a significant role in clinical diagnosis and treatment such as biomarker detection, fluorescence imaging-guided surgery, and photothermal/photodynamic therapy. In situ imaging of biomarkers depends on the spatial resolution of molecular probes. Nevertheless, the majority of currently available molecular fluorescent probes suffer from the drawback of diffusing from the target region. This leads to a rapid attenuation of the fluorescent signal over time and a reduction in spatial resolution. Consequently, the diffused fluorescent signal cannot accurately reflect the in situ information of the target. Self-immobilizing and self-precipitating molecular fluorescent probes can be used to overcome this problem. These probes ensure that the fluorescent signal remains at the location where the signal is generated for a long time. In this review, we introduce the development history of the two types of probes and classify them in detail according to different design strategies. In addition, we compare their advantages and disadvantages, summarize some representative studies conducted in recent years, and propose prospects for this field.


Thermo-tolerant phosphate-solubilizing microbes for multi-functional biofertilizer preparation.
In order to prepare the multi-functional biofertilizer, thermo-tolerant phosphate-solubilizing microbes including bacteria, actinomycetes, and fungi were isolated from different compost plants and biofertilizers. Except Streptomycesthermophilus J57 which lacked pectinase, all isolates possessed amylase, CMCase, chitinase, pectinase, protease, lipase, and nitrogenase activities. All isolates could solubilize calcium phosphate and Israel rock phosphate; various isolates could solubilize aluminum phosphate, iron phosphate, and hydroxyapatite. During composting, biofertilizers inoculated with the tested microbes had a significantly higher temperature, ash content, pH, total nitrogen, soluble phosphorus content, and germination rate than non-inoculated biofertilizer; total organic carbon and carbon-to-nitrogen ratio showed the opposite pattern. Adding these microbes can shorten the period of maturity, improve the quality, increase the soluble phosphorus content, and enhance the populations of phosphate-solubilizing and proteolytic microbes in biofertilizers. Therefore, inoculating thermo-tolerant phosphate-solubilizing microbes into agricultural and animal wastes represents a practical strategy for preparing multi-functional biofertilizer.


Early and late components of Epstein-Barr virus-associated membrane antigen in superinfected Daudi cells and their reactivity with sera from nasopharyngeal carcinoma patients.
Investigations were carried out on newly synthesized MA, VCA and EA in Daudi cells superinfected with the P3HR-1 strain of EBV and treated with trypsin to remove previously adsorbed MA-positive material from the cell surface. Synthesis of MA, VCA and EA was completely blocked by puromycin. A marked reduction in the frequency of MA-positive cells was observed in the infected cell cultures in the presence of either Ara-C or PA, but a fraction of the MA-positive cells was insensitive to the inhibitors. Differential absorption of an EBV antibody-positive human serum with Ara-C-treated or -untreated infected cells revealed two antigenically different components of MA: early (Ara-C-insensitive) and late (Ara-C-sensitive) MA. Three of five sera from patients with NPC, but none of five sera from normal adults, showed an apparent 'prozone' phenomenon in their reactivity against late but not early MA.


Evolution from a non-Fermi liquid Kondo lattice to intermediate valence behaviour in CeRhSn(1-x)In(x).
We present investigations of the magnetic and electric transport properties, specific heat, and electronic structure of the intermetallic and strongly correlated system of CeRhSn(1-x)In(x) compounds. The main goal of this paper is to determine the hybridization energy between the f electron and conduction electron states, V(cf), and its influence on the ground state properties of the system. The complementary experimental data are discussed on the basis of the Anderson model for a periodic Kondo lattice. CeRhSn is known as a non-Fermi liquid, while CeRhIn is a valence fluctuating system. We discuss the ground state properties of CeRhSn(1-x)In(x) and compare the results with those obtained for the doped Ce-based Kondo insulators.


The reactivity of galactose oxidase with snail galactans, galactosides and D-galactose-composed oligosaccharides.
The enzymic oxidation of snail galactans, of their first and second Smith degradation products and of some structurally related polysaccharides was studied. Lymnaea stagnalis galactan after one cycle of Smith degradation reacted best and native Helix pomatia galactan was almost inactive. Investigations on the structural requirements for oligosaccharides to bind to galactose oxidase showed that the branched tetrasaccharide, Gal-beta-1----6-[Gal-beta-1----3]-Gal-beta-1----1 L-Gro, in the terminal nonreducing position was the most complementary structure in the native galactan to associate with the enzyme. All nitrophenyl alpha-galactosides reacted better, and the ortho-form was 10-times more potent compared with this tetrasaccharide, indicative of the involvement of a hydrophobic region in binding. However, the beta-linked isomers were only equally or less reactive than galactose. The enzymic oxidation determined colorimetrically by transferring the peroxide formed to o-dianisidine ceased at a maximum typical for each substrate and independent of the reaction time. When the absolute turn-over rates for ortho- and para-nitrophenyl alpha-galactoside and for the beta-isomer were determined by HPLC, it could be demonstrated that the oxidation had not finished at the maximum of the colour reaction, but proceeded until the substrate was consumed. The initial speed of the colour reaction paralleled the absolute oxidation rate.


The Comprehensive Complication Index. Proposed modification to improve estimates of perioperative morbidity after radical cystectomy. A pilot study.
The aim of this article was to compare the 30-day morbidity after radical cystectomy comparing the prevalent Clavien-Dindo Classification (CDC) and the novel Comprehensive Complication Index (CCI). Additionally, we evaluated the correlation between particular clinical features and the severity of perioperative morbidity. A total of 42 patients were included into the study (33 men and 9 women) who underwent open radical cystectomy (RC) with bilateral lymphadenectomy for bladder cancer. The selection of complications was based on groundbreaking research on morbidity after RC. The assessment of perioperative complications was performed using the CDC and then the CCI. The CCI was found to be a significant upgrade in capturing cumulative morbidity in comparison to the CDC when used as the only evaluational tool. Using only the CDC may underestimate the severity of perioperative complications. Unfavorable clinical features e.g. older age, chronic kidney disease (CKD), persistent nodal (pN+) disease, prior abdominal and pelvic surgeries as well as smoking are of significant importance for the increase of the severity of perioperative complications.


Adrenal insufficiency in patients on long-term opioid analgesia.
Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain. Cross-sectional study of chronic pain patients on long-term opioid analgesia. Patients attending tertiary chronic pain clinics at the Western General Hospital, Edinburgh, treated with long-term opioid analgesia (n = 48) with no recent exposure to exogenous glucocorticoids. Four patients (8·3%) had basal morning plasma cortisol concentrations below 100 nmol/l, of whom three failed to achieve a satisfactory cortisol response to exogenous ACTH1-24 stimulation (peak cortisol >430 nmol/l). Basal cortisol was positively associated with age (R = 0·398, P = 0·005) and negatively associated with BMI (R = -0·435, P = 0·002). Suppression of the hypothalamic-pituitary-adrenal axis is present in a clinically significant proportion of chronic pain patients treated with opioid analgesia. Studies of larger populations should be conducted to better define the prevalence and potential clinical consequences of adrenal insufficiency in this context.


Acute effects of short-chain alkylglycerols on blood-brain barrier properties of cultured brain endothelial cells.
The blood-brain barrier (BBB) restricts drug penetration to the brain preventing effective treatment of patients suffering from brain tumours. Intra-arterial injection of short-chain alkylglycerols (AGs) opens the BBB and increases delivery of molecules to rodent brain parenchyma in vivo. The mechanism underlying AG-mediated modification of BBB permeability is still unknown. Here, we have tested the effects of AGs on barrier properties of cultured brain microvascular endothelial cells. The effects of two AGs, 1-O-pentylglycerol and 2-O-hexyldiglycerol were examined using an in vitro BBB model consisting of primary cultures of rat brain endothelial cells, co-cultured with rat cerebral glial cells. Integrity of the paracellular, tight junction-based, permeation route was analysed by functional assays, immunostaining for junctional proteins, freeze-fracture electron microscopy, and analysis of claudin-claudin trans-interactions. AG treatment (5 min) reversibly reduced transendothelial electrical resistance and increased BBB permeability for fluorescein accompanied by changes in cell morphology and immunostaining for claudin-5 and β-catenin. These short-term changes were not accompanied by alterations of inter-endothelial tight junction strand complexity or the trans-interaction of claudin-5. AG-mediated increase in brain endothelial paracellular permeability was short, reversible and did not affect tight junction strand complexity. Redistribution of junctional proteins and alterations in the cell shape indicate the involvement of the cytoskeleton in the action of AGs. These data confirm the results from in vivo studies in rodents characterizing AGs as adjuvants that transiently open the BBB.


Deep learning to automatically evaluate HER2 gene amplification status from fluorescence in situ hybridization images.
Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups.


Messenger RNA phenotyping for semi-quantitative comparison of glucocorticoid receptor transcript levels in the developing embryonic mouse palate.
A specific complex of glucocorticoid and receptor interacts with responsive genes in target tissues of developing palate and controls its morphogenesis. In order to examine developmental changes in glucocorticoid receptor gene expression during embryonic palate formation, variations in transcript levels have been determined using a simple semi-quantitative reverse transcription-polymerase chain reaction (PCR) procedure. Oligo (dT)16 was used as the primer for reverse transcription, and the amount of PCR product for glucocorticoid receptor was normalized against those for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin. We found that either GAPDH or beta-actin were suitable internal standards, and that the mRNA levels of glucocorticoid receptor undergoes a significant decrease of 30% at the developmental stage of embryonic mouse palatal shelf re-orientation. Immunolocalization of the receptor demonstrated a significant change in the distribution pattern of glucocorticoid receptor during the re-orientation stage of secondary palate formation. Our present data suggest that developmental variations in glucocorticoid receptor level control morphogenetic events of secondary palate formation.


MRI demonstration of impairment of the blood-CSF barrier by glucose administration to the thiamin-deficient rat brain.
Contrast-enhanced T1-weighted spin-echo magnetic resonance imaging (MRI) has demonstrated that Gd-diethylenetriaminepentaacetate (Gd-DTPA), which normally does not cross the blood-brain or blood-CSF barriers, does so approximately 40 min after administration of glucose to a vitamin B1 deficient rat. The period of the onset of this blood-CSF or blood-brain barrier dysfunction coincides with our previous observations of accumulation of glutamate or glutamate derivatives following an equivalent glucose load under identical conditions of thiamin deficiency, consistent with a relationship between these two observations. The dysfunction was reversed when a thiamin deficient animal was made thiamin replete.


Twitter Footprint and the Match in the COVID-19 Era: Understanding the Relationship between Applicant Online Activity and Residency Match Success.
The dramatic reduction of clinical and research activities within medical and surgical departments during COVID-19, coupled with the inability of medical students to engage in research, away rotations and academic meetings, have all posed important implications on residency match. Using Twitter application programming interface available data, 83,000 program-specific and 28,500 candidate-specific tweets were extracted for the analysis. Applicants to urology residency were identified as matched vs unmatched based on 3-level identification and verification. All elements of microblogging were captured through Anaconda Navigator. The primary endpoint was residency match, assessed as correlation to Twitter analytics (ie retweets, tweets). The final list of matched/unmatched applicants through this process was cross-referenced with internal validation of information obtained from the American Urological Association. A total of 28,500 English language posts from 250 matched and 45 unmatched applicants were included in the analysis. Matched applicants generally showed higher number of followers (median 171 [IQR 88-317.5] vs 83 [42-192], p=0.001), tweet likes (2.57 [1.53-4.52] vs 1.5 [0.35-3.03], p=0.048), and recent and total manuscripts (1 [0-2] vs 0 [0-1], p=0.006); 1 [0-3] vs 0 [0-1], p=0.016) in comparison to the unmatched cohort. On multivariable analysis, after adjusting for location, total number of citations and manuscripts, being a female (OR 4.95), having more followers (OR 1.01), individual tweet likes (OR 1.011) and total number of tweets (OR 1.02) increased overall odds of matching into a urology residency. Our study of the 2021 urology residency application cycle and use of Twitter highlighted distinct differences among matched and unmatched applicants and their respective Twitter analytics, highlighting a potential professional development opportunity offered by social media in underscoring applicants' profiles.


Familial DNA analysis and criminal investigation: Usage, downsides and privacy concerns.
Since the discovery of Deoxyribonucleic acid (DNA) capability in forensic investigation, it has been an important part of the criminal justice system. In most criminal cases DNA profile originating from evidence sample collected from the crime scene is compared with the DNA profile from the reference sample. However, when a reference sample is not available for comparison, familial DNA analysis can provide important investigation leads in a criminal investigation process by identifying an individual. Moreover, this analysis is also proving effective in the identification of ethnicity and ancestry of an individual. A number of different methodologies and software are being used for familial DNA analysis. This review describes the importance of familial DNA analysis, methodologies used for familial DNA searching and identification, and its advantages in forensic. Moreover, ethical, legal and social issues associated with familial DNA analysis have also been discussed along with future directions for the proper implementation of this technology.


Classification accuracy of the Quick Interactive Language Screener for preschool children with and without developmental language disorder.
This research examined the classification accuracy of the Quick Interactive Language Screener (QUILS) for identifying preschool-aged children (3;0 to 6;9) with developmental language disorder (DLD). We present data from two independent samples that varied in prevalence and diagnostic reference standard. Study 1 included a clinical sample of children (54 with DLD; 13 without) who completed the QUILS and a standardized assessment of expressive grammar (Syntax subtest from the Diagnostic Evaluation of Language Variation-Norm Referenced; Structured Photographic Expressive Language Test-Preschool 2nd Edition; or Structured Photographic Expressive Language Test-3 rd Edition). Study 2 included a community sample of children (25 with DLD; 101 without) who completed the QUILS and the Auditory Comprehension subtest of the Preschool Language Scales-5th Edition (PLS-5; Zimmerman et al., 2011). Discriminant analyses were conducted to compare classification accuracy (i.e., sensitivity and specificity) using the normreferenced cut score (< 25th percentile) with empirically derived cut scores. In Study 1, the QUILS led to low fail rates (i.e., high specificity) in children without impairment and statistically significant group differences as a function of children's clinical status; however, only 65% of children with DLD were accurately identified using the norm-referenced cutoff. In Study 2, 76% of children with DLD were accurately identified at the 25th percentile cutoff and accuracy improved to 84% when an empirically derived cutoff (<32nd percentile) was applied. Findings support the clinical application of the QUILS as a component of the screening process for identifying the presence or absence of DLD in community samples of preschool-aged children.


TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis.
TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage.


Organically modified layered magnesium silicates to improve rheology of reservoir drilling fluids.
Petroleum well drilling fluids are one of the most significant constituents in the subterranean drilling processes to meet an increasing global demand for oil and gas. Drilling fluids experience exceptional wellbore conditions, e.g. high temperature and high pressure that adversely affect the rheology of these fluids. Gas and oil well drilling operations have to adjourn due to changes in fluid rheology, since the drilling fluids may lose their effectiveness to suspend heavy particles and to carry drilled cuttings to the surface. The rheological properties of drilling fluids can be controlled by employing viscosifiers that should have exceptional stability in downhole environments. Here, we have developed next-generation viscosifiers-organically modified magnesium silicates (MSils)-for reservoir drilling fluids where organic functionalities are directly linked through the Si-C bond, unlike the industry's traditional viscosifier, organoclay, that has electrostatic linkages. The successful formation of covalently-linked hexadecyl and phenyl functionalized magnesium silicates (MSil-C16 and MSil-Ph) were confirmed by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA). Identical drilling fluid formulations were designed for comparison using MSils and a commercial viscosifier. The rheological properties of fluids were measured at ambient conditions as well as at high temperatures (up to 150 °C) and high pressure (70 MPa). Owing to strong covalent linkages, drilling fluids that were formulated with MSils showed a 19.3% increase in yield point (YP) and a 31% decrease in apparent viscosity (AV) at 150 °C under 70 MPa pressure, as compared to drilling fluids that were formulated with traditional organoclay. The higher yield point and lower apparent viscosity are known to facilitate and increased drilling rate of penetration of the fluids and an enhanced equivalent circulation density (ECD), the dynamic density condition, for efficient oil and gas wells drilling procedures.


What does distance matter? Leprosy control in West Nepal.
One of the major planks of leprosy control strategies is that distance from established treatment centres deters leprosy cases from seeking treatment. The integration of leprosy care with locally available primary health care services is therefore a common feature of leprosy control programmes. Within these guidelines, a National Leprosy Control Programme was established in Nepal in 1975, with intensive case-finding surveys and the provision of leprosy care in government basic health posts. A study of one district, Lamjung, in West Nepal suggests that far from being a deterrent, distance afforded welcome anonymity for leprosy cases anxious to disguise their diagnosis and thereby avoid the social ostracism which could result. Cases from ethnic groups in which the stigma of leprosy was high travelled farther for treatment. Gender differences in distance travelled suggest that women's mobility was restricted, but the local availability of care did not increase attendance for regular treatment. It is suggested that this was more the result of poor quality of care than fear of being known locally as a leprosy case.


A phased array coil for human cardiac imaging.
A prototype cardiac phased array receiver coil was constructed that comprised a cylindrical array and a separate planar array. Both arrays had two coil loops with the same coil dimensions. Data acquisition with the cylindrical array placed on the human chest, and the planar array placed under the back, yielded an overall enhancement of the signal-to-noise ratio (SNR) over the entire heart by a factor of 1.1-2.85 over a commercially available flexible coil and a commercially available four-loop planar phased array coil. This improvement in SNR can be exploited in cardiac imaging to increase the spatial resolution and reduce the image acquisition time.


The role of the cardiac sonographer in the evaluation of the heart transplant recipient.
The sonographer should have a basic understanding of the indications, surgical technique, survival rate, electrocardiographic findings, chest radiographic findings, and complications for orthotopic cardiac transplantation. The sonographer should also have a thorough understanding of the normal echocardiographic and Doppler findings in these patients and the possible echocardiographic and Doppler findings during acute early rejection. This article has presented those findings in a review form to enable the sonographer to consult the information presented before the echocardiographic and cardiac Doppler examination is carried out. In addition, a sample echocardiographic and cardiac Doppler worksheet has been provided.


Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson's disease.
Parkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not been investigated. We aim to characterize PD subtypes using a multimodal clustering approach based on cortical and subcortical gray matter (GM) volumes and FA measures. We included T1-weighted and diffusion-weighted MRI data from 62 PD patients and 33 healthy controls. We extracted mean GM volumes from 48 cortical and 17 subcortical regions using FSL-VBM, and the mean FA from 20 WM tracts using Tract-Based Spatial Statistics (TBSS). Hierarchical cluster analysis was performed with the PD sample using Ward's linkage method. Whole-brain voxel-wise intergroup comparisons of VBM and TBSS data were also performed using FSL. Neuropsychological and demographic statistical analyses were conducted using IBM SPSS Statistics 25.0. We identified three PD subtypes, with prominent differences in GM patterns and little WM involvement. One group (n = 15) with widespread cortical and subcortical GM volume and WM FA reductions and pronounced cognitive deficits; a second group (n = 21) with only cortical atrophy limited to frontal and temporal regions and more specific neuropsychological impairment, and a third group (n = 26) without detectable atrophy or cognition impairment. Multimodal MRI data allows classifying PD patients into groups according to GM and WM patterns, which in turn are associated with the cognitive profile.


Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vivo feasibility study.
Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.


Delayed inducible resistance against a leaf-chewing insect in four deciduous tree species.
Both mechanical damage to mountain birch foliage and rearing of moth larvae on the trees reduced the growth of Epirrita autumnata larvae reared on these trees in the following year. The effects of physical damage and some other cues from insects were additive. On bird cherry the performance of Epirrita larvae was equal on untreated trees and on trees artificially defoliated in the previous year, but larval growth was reduced on previously insect-damaged branches. With mountain ash just physical damage per se reduced the performance of Epirrita larvae. On Salix phylicifolia there were no significant differences in the growth or survival of Epirrita on untreated control bushes and on bushes with partial larval damage during the previous year. Among untreated control trees the growth and survivorship of Epirrita were higher on fast-growing willow and bird cherry than on the slow-growing mountain birch. Mountain birch and mountain ash, the two deciduous tree species adapted to nutrient-poor soils, showed delayed inducible resistance triggered by defoliation (artificial or insect-made). This supports the hypothesis that delayed inducible resistance may be a passive response due to nutrient-stress caused by defoliation. On the other hand, the additional increase in the resistance of mountain birch triggered by specific cues from insects suggests that this response may be an evolved defense against leaf-eating insects.


Abnormal breathing patterns.
In health, breathing is regular and the respiratory rate is sufficiency constant to be useful as a vital sign of health and disease. This regularity depends on a complex interplay of chemical and neural control systems that operate automatically to reset the rate and depth of breathing as changes occur in posture and activity, to adjust the level of ventilation so that changes in gas tensions and pH in the blood and in the brain intersitial fluid are exceedingly modest despite wide swings in metabolic rate and in environmental conditions, and to coordinate ventilation and circulation so that the requirements of individual tissues for O2 delivery and CO2 removal are satisfied. Two broad categories of disorders can result from malfunction of these systems (Table 1): (1) disproportionate ventilation (too high or too low) for the level of metabolic activity, thereby producing severe abnormalities in blood gas tensions or in acid-base balance, and (2) an irregular breathing pattern without eliciting gross changes in blood gas tensions or in acid-base balance. Because of the complexity of the control system, each of these categories represents a final common pathway that can be produced in different ways. In this presentation, we will attempt to describe the general features that characterize the operation of the control system and some new technics that make it possible to trouble-shoot the malfunctioning system in order to identify the mechanism(s) responsible for the abnormality in breathing pattern.


Effects of polyphenol extract from olive pomace on anoxia-induced endothelial dysfunction.
Anoxia modulates the expression of molecules associated with endothelial dysfunction and vascular diseases. Polyphenols have potent antioxidant properties due to their ability to modulate genes involved in oxidative tissue damage. In this study, we investigated the effect of polyphenol extract from olive pomace (PEOP) and its main constituents, Tyrosol and Oleuropein, on endothelial cells subjected to anoxia by evaluating the expression of molecules critical for endothelial function, proliferation and migration, and the signaling pathway involved. EAhy926 human endothelial cells were exposed to anoxic stress in the presence or absence of PEOP. Anoxia increased the nitric oxide (NO) level and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNFα). These effects were prevented by PEOP treatment in a dose-dependent manner. Moreover, PEOP prevented the proliferation and migration associated with anoxia in EAhy926 cells, down-regulated the levels of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type-1 MMP (MT1-MMP) and increased tissue MMP inhibitor-1 (TIMP-1) expression. Purified Oleuropein or Tyrosol restored to a basal level the anoxia-induced expression of MMP-9 and partially of MMP-2. The expression of TNFα was reduced by both polyphenols in a dose-dependent manner, but more efficiently by Tyrosol. Conversely, Oleuropein and Tyrosol had no significant effects on iNOS, COX-2 and TIMP-1 expression when used at the concentration found in PEOP. PEOP induced a time-dependent phosphorylation of p38 MAPK and ERK1/2 and inhibited anoxia-induced NF-κB activation. PEOP treatment restores the endothelial functions that are impaired by anoxia by regulating the expression of genes involved in proteolysis, angiogenesis and inflammation more efficiently than the single purified components. Therefore, the combined use of polyphenols, as in PEOP, could represent a powerful tool for the treatment and chemoprevention of endothelial dysfunction-associated vascular diseases.


Role of osteoclasts and interleukin-17 in the pathogenesis of rheumatoid arthritis: crucial 'human osteoclastology'.
Many papers have reported that osteoclasts play an important role in the pathogenesis of rheumatoid arthritis (RA); however, when we started to investigate the pathogenesis of RA, the roles of osteoclasts were not highlighted in RA bone resorption. In recent years, the number of articles on the roles of osteoclasts and interleukin (IL)-17 in the pathogenesis of RA has increased exponentially. In this review article, we describe our articles on the roles of osteoclasts and IL-17 in joint destruction in RA, from 1990 to 2011, and highlight a novel term, 'human osteoclastology', which we have used since 2008.


Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus.
Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability. NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5 ± 22.4% versus 16.3 ± 13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7 ± 17.8% versus 41.8 ± 15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments. The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.


Effects of baclofen and raclopride on reinstatement of cocaine self-administration in the rat.
At present there is no satisfactory treatment against relapse of drug-seeking behavior. Relapse can be modeled in laboratory animals using reinstatement procedures, whereby previously extinguished self-administration for a drug is reinstated by different factors, such as exposure to cues or drug priming. It is thought that activation of gamma-aminobutyric acid (GABA) B receptor complexes could represent a promising approach to pharmacotherapy for diminishing relapse potential with drugs possessing reinforcing properties. The effects of baclofen (a prototypic GABAB receptor agonist) on cue-induced cocaine reinstatement were evaluated in the rat with or without a priming injection of cocaine. The effects of raclopride (an antagonist of dopamine D2 receptors) were also evaluated. Cue-induced reinstatement under vehicle resulted in a significant increase in the number of presses on the active lever, as compared with extinction lever responding. This effect was accentuated in rats receiving a priming injection of cocaine (cocaine-plus-cue-induced reinstatement). Baclofen, at doses without effects on food-motivated operant behavior (2.5 and 5mg/kg i.p.), dose-dependently decreased the number of active lever presses during cue-induced reinstatement. Baclofen had slightly weaker effects on cocaine-plus-cue-induced reinstatement. Raclopride (0.08 and 0.15 mg/kg s.c.) had similar effects against cue-induced reinstatement although it failed to inhibit cocaine-plus-cue-induced reinstatement at the lower dose. Baclofen dose-dependently and selectively decreased reinstatement of cocaine self-administration. The data obtained provide support for the potential anti-craving efficacy of baclofen in the treatment of cocaine drug-seeking.


Concentrations and bioaccessibility of polycyclic aromatic hydrocarbons in wastewater-irrigated soil using in vitro gastrointestinal test.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants and contribute to the pollution of soil environment. Soil ingestion is of increasing concern for assessing health risk from PAH-contaminated soils because soil ingestion is one of the potentially important pathways of exposure to environmental pollutants, particularly relevant for children playing at contaminated sites due to their hand-to-mouth activities. In vitro gastro-intestinal tests imitate the human digestive tract, based on the physiology of humans, generally more simple, less time-consuming, and especially more reproducible than animal tests. This study was conducted to investigate the level of PAH contamination and oral bioaccessibility in surface soils, using physiologically based in vitro gastro-intestinal tests regarding both gastric and small intestinal conditions. Wastewater-irrigated soils were sampled from the metropolitan areas of Beijing and Tianjin, China, which were highly contaminated with PAHs. Reference soil samples were also collected for comparisons. At each site, four soils were sampled in the upper horizon at the depth of 0-20 cm randomly and were bulked together to form one composite sample. PAH concentrations and origin were investigated and a physiologically based in vitro test was conducted using all analytical grade reagents. Linear regression model was used to assess the relationship between total PAH concentrations in soils and soil organic carbon (SOC). A wide range of total PAH concentrations ranging from 1,304 to 3,369 mug kg(-1) in soils collected from different wastewater-irrigated sites in Tianjin, while ranging from 2,687 to 4,916 mug kg(-1) in soils collected from different wastewater-irrigated sites in Beijing, was detected. In general, total PAH concentrations in soils from Beijing sites were significantly higher than those from Tianjin sites, indicating a dominant contribution from both pyrogenic and petrogenic sources. Results indicated that the oral bioaccessibility of PAHs in small intestinal was significantly higher (from P < 0.05 to P < 0.001) than gastric condition. Similarly, the oral bioaccessibility of PAHs in contaminated sites was significantly higher (from P < or = 0.05 to P < 0.001) than in reference sites. Individual PAH ratios (three to six rings), a more accurate and reliable estimation about the emission sources, were used to distinguish the natural and anthropogenic PAH inputs in the soils. Results indicated that PAHs were both pyrogenic and petrogenic in nature. The identification of PAH sources and importance of in vitro test for PAH bioaccessibility were emphasized in this study. The oral bioaccessibility of individual PAHs in soils generally decreased with increasing ring numbers of PAHs in both the gastric and small intestinal conditions. However, the ratio of bioaccessibility of individual PAHs in gastric conditions to that in the small intestinal condition generally increased with increasing ring numbers, indicating the relatively pronounced effect of bile extract on improving the bioaccessibility of PAHs with relatively high ring numbers characterized by their high K ( ow ) values. Similarly, total PAH concentrations in soils were strongly correlated with SOC, indicating that SOC was the key factor determining the retention of PAHs in soils. Soils were contaminated with PAHs due to long-term wastewater irrigation. PAHs with two to six rings showed high concentrations with a significant increase over reference soils. Based on the molecular indices, it was suggested that PAHs in soils had both pyrogenic and petrogenic sources. It was also concluded that the oral bioaccessibility of total PAHs in the small intestinal condition was significantly higher than that in the gastric condition. Furthermore, the bioaccessibility of individual PAHs in soils generally decreased with the increasing ring numbers in both the gastric and small intestinal conditions. It is suggested that more care should be given while establishing reliable soil criteria for PAHs, especially concerning the health of children who may ingest a considerable amount of PAH-contaminated soil via outdoor hand-to-mouth activities.


Similar dose-dependence of motor neuron cell death caused by wild type human TDP-43 and mutants with ALS-associated amino acid substitutions.
TDP-43, a multi-functional DNA/ RNA-binding protein encoded by the TARDBP gene, has emerged as a major patho-signature factor of the ubiquitinated intracellular inclusions (UBIs) in the diseased cells of a range of neurodegenerative diseases. Mutations in at least 9 different genes including TARDBP have been identified in ALS with TDP-43 (+)-UBIs. Thus far, the pathogenic role(s) of the more than 30 ALS-associated mutations in the TARDBP gene has not been well defined. By transient DNA transfection studies, we show that exogenously expressed human TDP-43 (hTDP-43), either wild type (WT) or 2 different ALS mutant (MT) forms, could cause significantly higher apoptotic death rate of a mouse spinal motor neuron-like cell line (NSC34) than other types of cells, e.g. mouse neuronal Neuro2a and human fibroblast HEK293T cells. Furthermore, at the same plasmid DNA dose(s) used for transfection, the percentages of NSC34 cell death caused by the 2 exogenously expressed hTDP-43 mutants are all higher than that caused by the WT hTDP-43. Significantly, the above observations are correlated with higher steady-state levels of the mutant hTDP-43 proteins as well as their stabilities than the WT. Based on these data and previous transgenic TDP-43 studies in animals or cell cultures, we suggest that one major common consequence of the different ALS-associated TDP-43 mutations is the stabilization of the hTDP-43 polypeptide. The resulting elevation of the steady state level of hTDP-43 in combination with the relatively low tolerance of the spinal motor neurons to the increased amount of hTDP-43 lead to the neurodegeneration and pathogenesis of ALS, and of diseases with TDP-43 proteinopathies in general.


Linking gas and particle ejection dynamics to boundary conditions in scaled shock-tube experiments.
Predicting the onset, style and duration of explosive volcanic eruptions remains a great challenge. While the fundamental underlying processes are thought to be known, a clear correlation between eruptive features observable above Earth's surface and conditions and properties in the immediate subsurface is far from complete. Furthermore, the highly dynamic nature and inaccessibility of explosive events means that progress in the field investigation of such events remains slow. Scaled experimental investigations represent an opportunity to study individual volcanic processes separately and, despite their highly dynamic nature, to quantify them systematically. Here, impulsively generated vertical gas-particle jets were generated using rapid decompression shock-tube experiments. The angular deviation from the vertical, defined as the "spreading angle", has been quantified for gas and particles on both sides of the jets at different time steps using high-speed video analysis. The experimental variables investigated are 1) vent geometry, 2) tube length, 3) particle load, 4) particle size, and 5) temperature. Immediately prior to the first above-vent observations, gas expansion accommodates the initial gas overpressure. All experimental jets inevitably start with a particle-free gas phase (gas-only), which is typically clearly visible due to expansion-induced cooling and condensation. We record that the gas spreading angle is directly influenced by 1) vent geometry and 2) the duration of the initial gas-only phase. After some delay, whose length depends on the experimental conditions, the jet incorporates particles becoming a gas-particle jet. Below we quantify how our experimental conditions affect the temporal evolution of these two phases (gas-only and gas-particle) of each jet. As expected, the gas spreading angle is always at least as large as the particle spreading angle. The latter is positively correlated with particle load and negatively correlated with particle size. Such empirical experimentally derived relationships between the observable features of the gas-particle jets and known initial conditions can serve as input for the parameterisation of equivalent observations at active volcanoes, alleviating the circumstances where an a priori knowledge of magma textures and ascent rate, temperature and gas overpressure and/or the geometry of the shallow plumbing system is typically chronically lacking. The generation of experimental parameterisations raises the possibility that detailed field investigations on gas-particle jets at frequently erupting volcanoes might be used for elucidating subsurface parameters and their temporal variability, with all the implications that may have for better defining hazard assessment. The online version contains supplementary material available at 10.1007/s00445-021-01473-0.


Lipopolysaccharide and phorbol esters induce differentiation but have opposite effects on phosphatidylinositol turnover and Ca2+ mobilization in 70Z/3 pre-B lymphocytes.
We have recently shown that both lipopolysaccharide (LPS) and the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA) induce differentiation in the transformed murine pre-B lymphocyte cell line 70Z/3 by enhancing Na+-H+ exchange across the plasma membrane through an amiloride-sensitive transport system (Rosoff, P.M., Stein, L.F., and Cantley, L.C. (1984) J. Biol. Chem. 259, 7056-7060). These data suggested that the activation of protein kinase C indirectly by LPS and directly by TPA was the critical step in the initiation of differentiation in these cells. We extend these observations to show that LPS rapidly stimulates an increase in phosphatidylinositol turnover, leading to a rise in the levels of diacylglycerol and inositol 1,4,5-trisphosphate and a concomitant decrease in the amount of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. There is also a rapid elevation of intracellular free [Ca2+] which is independent of the presence of extracellular Ca2+ or Na+. These results suggest that the increase in cytosolic [Ca2+] is due to release of cation from internal stores. TPA, which also causes differentiation in these cells, and the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol, have opposite effects from LPS on both phosphatidylinositol turnover and cellular Ca+ mobilization. These data suggest that protein kinase C inhibits the activity of phospholipase C. Thus protein kinase C plays a pivotal role in the regulation of mitogen-induced differentiation in these cells by both transducing a positive stimulus to the Na+-H+ exchange system as well as feedback regulating its own stimulatory pathway.


BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin.
The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South America, where Amerindian founder effects and recent multiracial immigration are predicted to result in high genetic diversity. We describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean series of breast/ovarian cancer patients selected for young age at diagnosis or breast/ovarian cancer family history. The study series (134 patients) included 37 cases diagnosed within 40 years of age and no family history (any ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and c.5946delT in BRCA2). We found 24 deleterious mutations (BRCA1:16; BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and 17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T, c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72 variants of which 54 previously reported and 17 novel, 33 detected in an individual patient. Four missense variants of unknown clinical significance, identified in 5 patients, are predicted to affect protein function. While global and European variants contributed near 45% of the detected BRCA1/2 variation, the significant fraction of new variants (25/96, 26%) suggests the presence of a South American genetic component. This study, the first conducted in Argentinean patients, highlights a significant impact of novel BRCA1/2 mutations and genetic variants, which may be regarded as putatively South American, and confirms the important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi Jews.


Protection by salvianolic acid A against adriamycin toxicity on rat heart mitochondria.
It was found that salvianolic acid A (Sai A) has potent antioxidant activity. The effects of Sai A on adriamycin-induced heart mitochondrial toxicity of rats in vitro and on adriamycin antitumor activity are investigated in this article. Malondialdehyde (MDA) formation and membrane rigidification of rat heart mitochondria intoxicated with adriamycin were significantly reduced by Sai A. In the electron spin resonance (ESR) studies, Sai A has no significant effect on the formation of adriamycin semiquinone radicals (AQ.), while hydroxyl radicals generated by electron transfer from AQ. to H2O2 were scavenged by Sai A dose-dependently. On the other hand, Sai A was shown to have no effects on the antitumor activity of adriamycin in cultured L1210 ascitic tumor cells and in mice with P388 ascite tumor. These results indicate that Sai A protects against adriamycin induced heart mitochondrial toxicity of rats, while Sai A has no antagonizing effect on the antitumor activity of adriamycin.


Diet composition affects long-term zearalenone exposure on the gut-blood-liver axis metabolic dysfunction in mice.
Zearalenone (ZEN), one of the most contaminated Fusarium toxins worldwide, is very common in contaminating wheat, corn oil and other foods. People are more vulnerable to ZEN exposure with more daily caloric intake, yet little is known about the combined effect of different dietary patterns with mycotoxins. This study aimed to compare the effects of long-term ZEN exposure on the overall biochemical landscape of the "gut-blood-liver axis" under normal diet and high-fat diet (HFD) using a combined multi-omics approach. The results indicated that ZEN exposure, possibly via the phenylalanine metabolic pathway, led to dysbiosis of mouse flora, suppression of short-chain fatty acids (SCFAS) metabolism, systemic inflammatory responses, and disturbances in serum and liver metabolism, which were exacerbated in synergy with HFD and ultimately led to a more severe state of lipid metabolism in the liver. We further found that ZEN exposure attenuated the indole-3-propionic acid (IPA) metabolic pathway, enhanced 2-hydroxybutyric acid metabolism in serum, and attenuated β-alanine metabolism in liver which was positively correlated with the abundance of Prevotellaceae UCG-004, Prevotellaceae UCG-001, and Prevotellaceae NK3B31 groups. The results highlighted the damaging effects of ZEN on the gut-blood-liver axis under different dietary patterns, which might serve as a reference for future studies exploring the combined effects of fungal toxins and multiple dietary patterns.


A belt transect setting strategy for mark-recapture experiments to evaluate the 1D diffusion coefficient of beached litter in the cross-shore direction.
We propose a belt transect setting strategy for mark-recapture experiments (MREs) to evaluate the time-independent 1D diffusion coefficient (〈Dp0〉) of marine litter in the cross-shore direction that determines the backwashing flux of the litter, based on two-year MREs for plastic floats (PFs) on Wadahama Beach, Nii-jima Island, Japan. When the alongshore width of the belt transect (Lt) was of the order of, or longer than, the length scale of wave-induced nearshore current circulation (Lc), the PFs were rarely transported alongshore across the selected transects prior to being backwashed offshore. Thus, the transect residence time became longer and showed a much weaker dependence on the transect position, in contrast to when Lt was even shorter than Lc. We therefore obtained the diffusion coefficients close to the value of (〈Dp0〉) when we set Lt to the order of, or longer than, Lc.


Elongation factor EF-1 alpha from Artemia is specifically labeled at Lys-63 by the guanine nucleotide analog pyridoxal-5'-diphospho-5'-guanosine.
We have synthesized the guanine nucleotide analog pyridoxal-5'-diphospho-5'-guanosine. This compound specifically modifies a single lysine residue in elongation factor 1 alpha from Artemia, indicating that this residue is in close contact with the reactive part of the guanine nucleotide analog. This result is discussed in terms of the structure of the nucleotide-binding domain of the factor.


In vitro gastrointestinal evaluation of a juçara-based smoothie: effect of processing on phenolic compounds bioaccessibility.
In the present work, the bioaccessibility of the main phenolic compounds of a juçara, banana and strawberry homogenized smoothie (control), subjected to pasteurization and sonication, was evaluated. The smoothie was also evaluated in terms of its main chemical and physical characteristics. Pasteurized smoothie showed higher apparent viscosity, as well as higher initial shear stress when compared to the control and sonicated samples. The increase in the apparent viscosity of the pasteurized smoothie was associated with the smaller particle size of this sample (68 μm). These characteristics conferred to the pasteurized smoothie higher physical stability than the control and sonicated smoothies. Phenolic compounds bioaccessibility was higher in the pasteurized and sonicated smoothies than in the control sample, which confirmed the positive effect of the treatments for the preservation of these compounds after gastrointestinal digestion. Compared to the sonication process, the pasteurization provided higher total phenolic compounds bioaccessibility (47%), as well as of ferulic (16%) and ellagic (80%) acids. Antioxidant capacity was higher in gastric digest for all the samples evaluated by ABTS assay. These results confirm the importance of processing on the physical stability and phenolic compounds bioaccessibility of the juçara-based smoothie, standing out the thermally treated product.


Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide combination in treating stage 2 hypertensive patients.
The objective of this study was to assess the effects of valsartan or olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ) in the treatment of stage 2 hypertension. 180 patients with diastolic blood pressure (DBP) ≥ 99 and < 110 mm Hg were treated with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients whose blood pressure (BP) was not controlled, were randomized to the combination of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg + amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks. At the end of each period, clinical and ambulatory BP measurements were recorded. Both triple combinations produced greater ambulatory and clinical SBP/DBP reduction than dual therapy. However, mean reduction from baseline in the valsartan + amlodipine + HCTZ-treated patients was significantly greater than in the olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the add-on effect of valsartan was significantly greater than that of olmesartan, the difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 - 3.51)/3.0 (95% CI 0.59 - 3.34) mm Hg, p < 0.01). The addition of valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of olmesartan.


Measuring merit in animal research.
Merit review of scientific projects involving laboratory animals is a central issue in the current debate over the ethics of animal experimentation. In this essay, I examine several conceptual, regulatory, and practical problems inherent in the merit review process. Contemporary challenges to the existing merit review system and suggestions for reform are also discussed. The essay concludes with comments on legal and political questions relevant to the future of merit assessment.


The relation between chronotype and treatment outcome with light therapy on a fixed time schedule.
Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression in a seasonal pattern. The therapy of choice is light therapy (LT). It is suggested that LT should be administered relative to the chronotype of the patient, with the optimal timing earlier for morning than for evening types. This study aims to retrospectively investigate the relation between chronotype and the effect of LT on a fixed time in the morning in a population of SAD patients. Data from four different studies conducted at the University Center of Psychiatry in Groningen, the Netherlands was used. Data from 132 patients was used (103 women). Depression score was determined by a structured interview (SIGH-SAD) prior to LT and after LT. Prior to LT morningness/eveningness preference of the patient was determined by the 'Morningness/Eveningness Questionnaire' (MEQ). All patients received LT at 8:00 AM at the clinic, independent of chronotype. Patients had an average MEQ score of 51.5±8.2. There was no significant relationship between MEQ score and therapy success as measured with the SIGH-SAD (F2,129=0.05, ns). When patients were divided by chronotype (ranging from definite morning to moderate evening) no significant relation between MEQ score and therapy success was found (F2,129=0.02, ns). Retrospective design. The lack of a significant relationship between chronotype, as measured with the MEQ, and therapy success with LT at a fixed timepoint may indicate that the anti-depressive effect of morning light in SAD patients is not explained by a phase shift of the biological clock.


Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks.
Temporal precision in spike timing is important in cortical function, interactions, and plasticity. We found that, during periods of recurrent network activity (UP states), cortical pyramidal cells in vivo and in vitro receive strong barrages of both excitatory and inhibitory postsynaptic potentials, with the inhibitory potentials showing much higher power at all frequencies above approximately 10 Hz and more synchrony between nearby neurons. Fast-spiking inhibitory interneurons discharged strongly in relation to higher-frequency oscillations in the field potential in vivo and possess membrane, synaptic, and action potential properties that are advantageous for transmission of higher-frequency activity. Intracellular injection of synaptic conductances having the characteristics of the recorded EPSPs and IPSPs reveal that IPSPs are important in controlling the timing and probability of action potential generation in pyramidal cells. Our results support the hypothesis that inhibitory networks are largely responsible for the dissemination of higher-frequency activity in cortex.


Kinetic characterization of l-[(3)H]glutamate uptake inhibition and increase oxidative damage induced by glutaric acid in striatal synaptosomes of rats.
Glutaric acidemia type I (GA-I) is an inherited metabolic disease characterized by accumulation of glutaric acid (GA) and striatal degeneration. Although growing evidence suggests that excitotoxicity and oxidative stress play central role in the neuropathogenesis of this disease, mechanism underlying striatal damage in this disorder is not well established. Thus, we decided to investigate the in vitro effects of GA 10nM (a low concentration that can be present initial development this disorder) on l-[(3)H]glutamate uptake and reactive oxygen species (ROS) generation in synaptosomes from striatum of rats. GA reduced l-[(3)H]glutamate uptake in synaptosomes from 1 up to 30min after its addition. Furthermore, we also provided some evidence that GA competes with the glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC), suggesting a possible interaction of GA with glutamate transporters on synaptosomes. Moreover, GA produced a significant decrease in the V(MAX) of l-[(3)H]glutamate uptake, but did not affect the K(D) value. Although the GA did not show oxidant activity per se, it increased the ROS generation in striatal synaptosomes. To evaluate the involvement of reactive species generation in the GA-induced l-[(3)H]glutamate uptake inhibition, trolox (0.3, 0.6 and 6muM) was added on the incubation medium. Statistical analysis showed that trolox did not decrease inhibition of GA-induced l-[(3)H]glutamate uptake, but decreased GA-induced reactive species formation in striatal synaptosomes (1, 3, 5, 10, 15 and 30min), suggesting that ROS generation appears to occur secondarily to glutamatergic overstimulation in this model of organic acidemia. Since GA induced DCFH oxidation increase, we evaluate the involvement of glutamate receptor antagonists in oxidative stress, showing that CNQX, but not MK-801, decreased the DCFH oxidation increase in striatal synaptosomes. Furthermore, the results presented in this report suggest that excitotoxicity elicited by low concentration of GA, could be in part by maintaining this excitatory neurotransmitter in the synaptic cleft by non-competitive inhibition of glutamate uptake. Thus the present data may explain, at least partly, initial striatal damage at birth, as evidenced by acute bilateral destruction of caudate and putamen observed in children with GA-I.


Surgical atrial septal defect closure after interventional occluder placement: incidence and outcome.
Closure of ostium secundum atrial septal defects is generally performed by using an interventional approach. We evaluated the outcome of patients requiring secondary surgical therapy. From September 1996 until December, 2005, 418 patients received interventional and 297 patients underwent surgical closure of an ostium secundum atrial septal defect at our center. Another 15 patients (local, 5; regional, 5; and national, 5 referrals) had complications after occluder placement, and they form the study population. Indications for surgical repair in these 15 patients were dislocation of the occluder in 5, neurologic events after occluder placement in 5, residual defects in 4, and sepsis with questionable occluder infection in 1 patient. A total of 7 patients had neurologic events, 5 of embolic origin. The interval between interventional occluder placement and definitive surgical repair was 319 +/- 416 days (median 123 days; range 0-1395 days). Patient age at operation was 34.9 +/- 18.6 years. Nine patients were operated on via an anterolateral minithoracotomy, and 6 received a conventional sternotomy. One patient with sepsis underwent abdominal surgery on postoperative day 1 and subsequently died of multiorgan failure; there was no proof of occluder endocarditis. At 2.2 +/- 1.9 years of follow-up, all other patients had returned to full-time work without residual neurologic impairment. Complications may arise after interventional ostium secundum atrial septal defect closure. This must be evaluated against the extremely low risk of a standard surgical closure. The functional outcome after secondary surgical ostium secundum atrial septal defect closure with removal of an occluder system is excellent.


Clivus chordoma in childhood.
A 9-year-old boy with mild left hemiparesis and left abducens nerve palsy was found to have chordoma of the clivus. Magnetic resonance imaging (MRI) was most useful not only for diagnosis but also for selection of operative approaches. The tumor was subtotally resected by a transoral-transpharyngeal approach followed by a retroauricular retromastoid craniotomy, and postoperative radiation therapy was administered. Intracranial chordomas are rare in children; only 12 cases have previously been reported in detail. Eleven patients were male and one was female. Progressive cranial nerve involvement and long tract signs without increased intracranial pressure constitute the cardinal symptomatology of intracranial chordomas, but a separation of cranial sutures and enlargement of the head may be seen in children. The role of MRI in diagnosis and patient management cannot be overemphasized.


Genetic information and life insurance: a proposal for an ethical European policy.
Developments in molecular biology will enable development of tests for genetic predisposition to multifactorial diseases. People identified with increased risk might be able to prevent or delay the onset of illness by medical treatment and/or changing their environmental exposure. But tests might also help organizations, such as employers, insurers, and government bodies, to minimize their future economic risks. This article searches for an ethical and feasible European policy for the use of genetic information in life insurance. It first argues that genetic information is not so relevantly different from at least one other kind of medical information, that of HIV infection, that it justifies unlike policy treatment. European life insurance is then claimed to be a non-primary social good which should be handled by the private market. The problem of adverse selection is argued to be a reasonably serious threat. Insurers should therefore be allowed to demand some genetic risk information in order to secure the sustainability of insurance schemes. However, the moral principles and values of autonomy, privacy, non-discrimination, non-deterrence, solidarity and confidentiality, put limits on insurers justified information demands. The article ends up advocating a regime of limited community-rated private life insurance, first proposed by a Dutch committee. It stipulates that insurers should be forbidden to demand genetic tests as a condition for an insurance contract, but be allowed to ask for existing genetic information when the sought insurance cover is above a certain limit.


Alcohol and breast cancer.
We examined breast cancer incidence in a cohort of about 69,000 women who answered detailed questions about alcohol consumption from 1979 to 1984. Among women with no prior cancer, breast cancer had developed in 303 by the end of 1984 for an age-adjusted incidence of 1.3/1,000 person years of follow-up. In analysis controlling only for age there was a progressive increase in breast cancer incidence corresponding to each higher level of reported alcohol consumption. In multivariate analyses controlling for age, race, body mass, and smoking, the relative risk at 1-2 drinks/day was 1.5 (95% confidence interval (CI) 1.0-2.3), at 3-5 drinks/day was 1.5 (95% CI 0.8-2.8), and at 6 or more drinks/day was 3.3 (95% CI 1.2-9.3). Past drinkers tended to have been heavier drinkers than current drinkers and had a relative risk of 2.2 (95% CI 1.2-3.9). Study of wine, beer, and liquor use did not suggest that any particular alcoholic beverage was responsible. Significant associations with heavy alcohol consumption were strongest among white and postmenopausal women. This study adds support to the growing evidence that alcohol may be a risk factor for development of breast cancer.


[Vaccinations].
Vaccination is considered one of the most important achievements of modern medicine and has saved millions of lives. As a result, the age-old fear of severe or fatal infectious diseases has largely been forgotten in society; however, the pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows how quickly this fear can return. Also, many people have reservations about medical measures, especially if they are directed against vague dangers. Paradoxically, the success of vaccinations jeopardizes the acceptance. To counteract this development, this article provides information on basic vaccination principles, legal frameworks and components of vaccines. It explains the most important categories, goals, core elements of vaccination programs and the most important recommendations of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO). It explains the current state of knowledge with respect to required resources, assessment of vaccine reactions, complication management and possible vaccine damage.


Roles of centromedian parafascicular nuclei of thalamus and cholinergic interneurons in the dorsal striatum in associative learning of environmental events.
The thalamus provides a massive input to the striatum, but despite accumulating evidence, the functions of this system remain unclear. It is known, however, that the centromedian (CM) and parafascicular (Pf) nuclei of the thalamus can strongly influence particular striatal neuron subtypes, notably including the cholinergic interneurons of the striatum (CINs), key regulators of striatal function. Here, we highlight the thalamostriatal system through the CM-Pf to striatal CINs. We consider how, by virtue of the direct synaptic connections of the CM and PF, their neural activity contributes to the activity of CINs and striatal projection neurons (SPNs). CM-Pf neurons are strongly activated at sudden changes in behavioral context, such as switches in action-outcome contingency or sequence of behavioral requirements, suggesting that their activity may represent change of context operationalized as associability. Striatal CINs, on the other hand, acquire and loose responses to external events associated with particular contexts. In light of this physiological evidence, we propose a hypothesis of the CM-Pf-CINs system, suggesting that it augments associative learning by generating an associability signal and promotes reinforcement learning guided by reward prediction error signals from dopamine-containing neurons. We discuss neuronal circuit and synaptic organizations based on in vivo/in vitro studies that we suppose to underlie our hypothesis. Possible implications of CM-Pf-CINs dysfunction (or degeneration) in brain diseases are also discussed by focusing on Parkinson's disease.


Brief Report: First Identification of Intrafamilial Recurrence of Blau Syndrome due to Gonosomal NOD2 Mosaicism.
Blau syndrome is characterized by noncaseating granulomatous arthritis, dermatitis, and uveitis, and results from gain-of-function NOD2 mutations. This study was undertaken to identify the genetic cause of the disease in a family with 3 members with Blau syndrome. We studied a family with 3 affected members across 2 consecutive generations. The children's symptoms started early (at 6 and 7 months of age) and included polyarthritis, dermatitis, uveitis, and fever. In contrast, the father's symptoms started later (at 22 years of age) and included noncaseating granulomatous dermatitis and uveitis. We analyzed the NOD2 gene in all patients by both the Sanger method of DNA sequencing and amplicon-based deep sequencing using an Ion Torrent PGM platform. Sanger chromatograms revealed the heterozygous c.1001G>A transition in both children, which resulted in the p.Arg334Gln mutation that causes Blau syndrome. In contrast, the father's chromatograms revealed a small peak of adenine at the c.1001 position, suggesting the presence of a somatic NOD2 mutation. To evaluate this hypothesis, we performed amplicon-based deep sequencing using DNA from different tissues, which confirmed a variable degree (0.9-12.9%) of somatic NOD2 mosaicism. The previous detection of the NOD2 mutation in his daughters strongly suggests the presence of gonosomal (somatic plus gonadal) NOD2 mosaicism in the father. Comparative analyses with Blau syndrome patients carrying the germline p.Arg334Gln NOD2 mutation revealed late onset of the disease, a mild inflammatory phenotype, and an absence of complications in patients with NOD2 mosaicism. This is the first description of gonosomal NOD2 mosaicism as the cause of intrafamilial recurrence of Blau syndrome. Our findings also indicate that Blau syndrome includes more diverse and milder phenotypes than previously described.


[Seat belt related abdominal injuries (author's transl)].
Seat belts reduce the severity of trauma in car accidents. There is a definite decrease in the percentage of head injuries, while abdominal lesions seem to increase. Experimental and clinical investigations show a predominance of abdominal wall injuries and liver ruptures. The seat belt syndrome requires close observation of the patient in the intensive care unit. An increasing number of late intestinal obstructions after a seat belt injury due to lesions of the intestinal wall are reported.


Effect of biocomposite production factors on the development of an eco-friendly chitosan/alginate-based adsorbent with enhanced copper removal efficiency.
Nowadays, wastewater treatment is a critical concern, particularly regarding the removal of heavy metals through adsorption methods. Extensive research has been conducted on obtaining high-yield and environmentally friendly adsorbents. Natural polymer adsorbents especially have shown promise in ion and organic molecule adsorption. To enhance the practical applicability of adsorbents, the combination of biopolymers to form biocomposites is a promising alternative. In this study, adsorbents based on a 1:1 wt./wt. of chitosan (CS) and alginate (SA) were prepared. The influence of the regeneration route and drying conditions on the copper adsorption capacity was investigated, along with reaction parameters such as contact time, adsorbent particle size, and pH. The highest adsorption capacity was observed in the composite material obtained through a one-pot regeneration process and freeze-dried. The CSAR3L sample exhibited a remarkable adsorption capacity of 288 mg Cu(II)/g after 360 min at 25 °C. The synergistic effect between the CS and SA precursors was confirmed by analyzing the individual precursors and their mechanical mixture. The initial adsorption rates at pH 6 followed the order: CSAR3-L > Bk-CSR3L > Bk-SAR3L + Bk-CSR3L > Bk-SAR3L. The physicochemical and morphological properties of the materials were studied by FTIR, XRD, DLS, XPS, optical microscopy, EDS-SEM, elemental chemical analysis, and TGA-DTG. The utilization of different drying methods resulted in the formation of calcium carbonate crystalline phases in the as-prepared materials, thus creating substantial adsorption active sites. After the adsorption process, hydroxylated copper sulfate phases and a significant decrease in calcium concentration were observed, indicating that an ion exchange adsorption mechanism occurred. The analysis of adsorption kinetics and the shape of the adsorption isotherms, in agreement with the characterization results, suggested the presence of multiple active sites and the formation of a chemisorption monolayer.


Characterization of biological pathways associated with semen traits in the Thai multibreed dairy population.
The objective of this research was to characterize biological pathways associated with semen volume (VOL), number of sperm (NS), and sperm motility (MOT) of dairy bulls in the Thai multibreed dairy population. Phenotypes for VOL (n = 13,535), NS (n = 12,773), and MOT (n = 12,660) came from 131 bulls of the Dairy Farming Promotion Organization of Thailand. Genotypic data consisted of 76,519 imputed and actual single nucleotide polymorphisms (SNP) from 72 animals. The SNP variances for VOL, NS, and MOT were estimated using a three-trait genomic-polygenic repeatability model. Fixed effects were contemporary group, ejaculate order, age of bull, ambient temperature, and heterosis. Random effects were animal additive genetic, permanent environmental, and residual. Individual SNP explaining at least 0.001% of the total genetic variance for each trait were selected to identify associated genes in the NCBI database (UMD Bos taurus 3.1 assembly) using the R package Map2NCBI. A set of 1,999 NCBI genes associated with all three semen traits was utilized for the pathway analysis conducted with the ClueGO plugin of Cytoscape using information from the Kyoto Encyclopedia of Genes and Genomes database. The pathway analysis revealed seven significant biological pathways involving 127 genes that explained 1.04% of the genetic variance for VOL, NS, and MOT. These genes were known to affect cell structure, motility, migration, proliferation, differentiation, survival, apoptosis, signal transduction, oxytocin release, calcium channel, neural development, and immune system functions related to sperm morphology and physiology during spermatogenesis.


Translating evidence into policy in China: opportunities and challenges.
Research and evidence are critical for the formulation of policies and practices in support of health care. In the past two decades, the Chinese Clinical Epidemiology Network has been promoting evidence-based policy making in China. Evidence-based policy has become a major part of the government's approach to policy making. The current article addresses the translation of evidence into health policies based on the expansion of evidence-based medicine in China. It also discusses the opportunities and challenges for certain evidence to be considered in policy making and practice in the future.


Determination of antibiotics from soil by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry.
A method for the analysis of several macrolide and ionophore antibiotics, as well as tiamulin, from soil was developed using pressurized liquid extraction (PLE), reversed-phase liquid chromatography and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry (LC-APCI+-MS-MS). The analytes were extracted from soil by PLE in 30 min and the extracts were cleaned up by solid-phase extraction (SPE) on a diol SPE cartridge. Liquid chromatographic (LC) separation of the antibiotics was achieved in 35 min. Recovery experiments were performed using spiked soil and concentrations varying from 1 to 2000 microg/kg. By using a macrolide internal standard the recovery rates for the macrolides erythromycin and roxithromycin ranged from 43 to 94% (RSD 20-23%), for the ionophore salinomycin the recovery rate was 76% (RSD 29%), while the pleuromutilin tiamulin was completely recovered. The limits of detection ranged from 0.2 to 1.6 microg/kg. In soil samples a maximum concentration of 0.7 microg/kg tiamulin was found.


Memory persistence of rats in a radial maze varies with training procedure.
Different estimations of the time-course of spatial working memory have been reported. Some authors found working memory in the radial maze to be relatively long lasting, while others found more rapid exponential decay. In the present experiments it was attempted to account for the conflicting results by investigating the effects of different training procedures. Two types of training were examined under the same circumstances. A group of seven rats was given a series of delayed trials (5, 20, 60, and 120 min). Every delay was repeated at least four times and the delays were presented in an ascending order. The number of errors decreased at every delay except the last one (120 min), where error levels were constant (.50 errors/trial). The good performance was not based on use of intramaze cues or response chaining. In another group of seven rats the same delays were introduced in a quasi-random order and alternated with uninterrupted trials. The number of errors increased exponentially with the length of the delay. However, when this procedure was repeated, the number of errors decreased. These results suggest that training with delayed trials is a major factor to account for the differences in reports of memory persistence in the radial maze.


[Intestinal parasitoses in preschool children of the slum communities of the city of Rio de Janeiro, Brazil].
Prevalence of intestinal parasites was investigated in 1381 low-income children under five years of age from March 1990 to October 1991 in the city of Rio de Janeiro, Brazil. Stool tests were run using the Blagg et al. method. Observed prevalence of infection was 54.5%. The most frequent parasites were Giardia lamblia and Ascaris lumbricoides (25.0% of the children). A significant statistical difference (p<0.05) was demonstrated between age and infection according to the species of parasite studied. Infection rates demonstrated the need for control of parasites in these child.


Internal iliac artery ligation in post-partum hemorrhage.
Between 1978 and 1986, internal iliac artery ligation was performed on eight patients undergoing treatment for severe post-partum hemorrhage, and disseminated intra-vascular coagulation (DIVC) combined with causal pathology was detected in five patients. This procedure was effective in controlling bleeding in eight patients and no hysterectomy was necessary. Post-operative follow-up was uncomplicated in six patients. One patient suffered from post-operative occlusion. Another patient suffered from renal failure, due to secondary cortical renal necrosis. Surgery is usually simple and does not pose any technical problems. This technique allows for the conservation of the reproductive functions, and two of the women became pregnant at a later stage. Obstetric hysterectomy can be avoided by using this technique. It is recommended in cases where DIVC does not respond to medical treatment and can furthermore be used by all surgeons.


Synthesis of (+/-) 8,12-trans-delta5-en-cis-9-keto-13,14-en-trans-15-R,S-hydroxyprostanoic acid methyl ester.
The synthesis of the title compound (X) is easily achieved by suitable transformations of the lateral chains of the 1-ethylenedioxy-2-allyl--trans-3-cyclopentane acetic acid (II).


Coronary Computed Tomography Angiography Derived Fractional Flow Reserve and Plaque Stress.
Fractional flow reserve (FFR) measured during invasive coronary angiography is an independent prognosticator in patients with coronary artery disease and the gold standard for decision making in coronary revascularization. The integration of computational fluid dynamics and quantitative anatomic and physiologic modeling now enables simulation of patient-specific hemodynamic parameters including blood velocity, pressure, pressure gradients, and FFR from standard acquired coronary computed tomography (CT) datasets. In this review article, we describe the potential impact on clinical practice and the science behind noninvasive coronary computed tomography (CT) angiography derived fractional flow reserve (FFRCT) as well as future applications of this technology in treatment planning and quantifying forces on atherosclerotic plaques.


Hereditary and non-hereditary microangiopathies in the young. An up-date.
In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total.