The Mu transpositional enhancer can function in trans: requirement of the enhancer for synapsis but not strand cleavage.
The phage Mu transpositional enhancer has been previously shown to stimulate the initial rate of the Mu DNA strand transfer reaction by a factor of 100. We now show that the Mu enhancer can function in trans on an unlinked DNA molecule. This activity is greatly facilitated by the presence of a free DNA end proximal to the enhancer element. Function of the enhancer in trans does not alter either the requirement for donor DNA supercoiling or for the two Mu ends to be in their proper orientation on the donor plasmid. An important consequence of these findings is that we have been able to evaluate directly the step in the transposition reaction for which the enhancer is required. We show that the role of the enhancer is limited to promoting productive synapsis; efficient strand cleavage can occur in the absence of the enhancer.


"Sleights of mind": delusions, defences, and self-deception.
Two different modes of theorising about delusions are explored. On the one hand is the motivational approach, which regards delusions as serving a defensive, palliative, even potentially adaptive function. On the other, is the cognitive deficit approach, which conceptualises delusions as explicitly pathological, involving abnormalities in ordinary cognitive processes. The former approach, prominently exemplified by the psychoanalytic tradition, was predominant historically, but has been challenged in recent years by the latter. Some grievances against psychoanalytic theory are briefly discussed, and it is argued that although the reasons for psychoanalysis falling into scientific disrepute are partly justified, the psychodynamic notion that motivation has access to the mechanisms of belief formation is of potentially crucial theoretical utility. A variety of possible syntheses of the two theoretical modes are therefore explored, in the belief that the most comprehensive account of delusions will involve a theoretical unification of both styles of explanation. Along the way, an attempt is made to locate the notions delusion, defence, and self-deception in a shared theoretical space.


Evolution of pedal digit orientation and morphology in relation to acquisition and secondary loss of the adhesive system in geckos.
Among geckos, the acquisition of the adhesive system is associated with several morphological changes of the feet that are involved in the operation of the adhesive apparatus. However, analyses using a comparative framework are lacking. We applied traditional morphometrics and geometric morphometric analysis with phylogenetic comparative methods to morphological data, collected from X-ray scans, to examine patterns of morphological evolution of the pes in association with the gain and loss of adhesive capabilities, and with habitat occupancy among 102 species of gecko. Padbearing gecko lineages tend to have shorter digits and greater inter-digital angles than padless ones. Arboreal and saxicolous species have shorter digits than terrestrial species. Our results suggest repeated shifts that converge upon a similar padbearing morphology, with some modifications being associated with the habitat occupied. We demonstrate that functional innovation and habitat can operate on, and influence, different components of foot morphology.


GIS analysis of land cover changes on the territory of the Prokuplje Municipality.
The monitoring of the territory of Prokuplje Municipality was done based on 1 : 25,000 topographic maps in three different time periods (1969, 1974, and 1984) and land cover map in 2012. Analogous topographic maps done in 1969, 1974, and 1984 were used, while in 2012 the land cover map obtained by using CORINE-like approach was used. Topographic maps are developed by aerial campaign, and today they are replaced by satellite images. Topographic maps were scanned, and raster form was transformed to vector data with Geo Media Professional 6.1 and Global Mapper software. The monitoring in the period of 1969-2012, on the area of 758300000 m(2), was performed, where some parameters were analyzed. In particular, the changes of natural resources, primarily forest lands, were observed as well as the type of land susceptible to primary erosion, including the level of urbanization and level of agricultural land. The obtained results clearly showed changes in forestation within the 43-year-long period, as well as changes in primary erosion and urbanization, while at the level of agricultural land, slight changes were found. The paper also involved transition of social factors from 1969 to 2012, expressed as a change between the earth and forest layer.


Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.
We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.


Virus load and neuropathology in the FIV model.
The FIV (feline immunodeficiency virus) induces in cats brain changes presenting similarities with those observed in human immunodeficiency virus infection. This FIV model was used to study the relationship between viral load in brain, in lymphoid organs and central nervous system (CNS) changes during the early and late stages of infection. Early brain changes were analyzed in animals experimentally infected with two different FIV isolates and sacrificed at 7 and 15 days, 1, 2, 6, and 12 months post inoculation (p.i.). Late CNS abnormalities were analyzed in naturally FIV-infected cats referred to the Veterinary School of Nantes. For each animal, one cerebral hemisphere was fixed and examined using routine techniques. The characterization of FIV replicating cells by in situ hybridization was performed on the other half frozen hemisphere on sections performed in the anterior and the median regions of the brain. During the early stages of infection, moderate gliosis with glial nodules and sometimes white matter pallor and meningitis were associated with few infected cells scattered in the brain. Infection was an early event as infected cells could be detected in brain at 7 p.i. For each cat, these findings were found identical in the two analyzed areas. During the late stages, brain lesions and the number of virus replicating cells increased especially in animals with perivascular infiltrates. The multinucleated giant cells encephalitis was never observed and the number of FIV replicating cells scattered in the whole brain was always low. This discrepancy between the number of replicating cells and the brain lesions, corroborates the hypotheses suggesting that brain injuries may be mediated via diffusive factors and amplification processes through cytokine cascades and cell activations.


HIV-Positive-to-HIV-Positive Liver Transplantation.
Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients.


Development and validation of a novel multiplexed DNA analysis system, InnoTyper® 21.
We report here a novel multiplexed DNA analysis system consisting of 20 Alu markers and Amelogenin for analysis of highly degraded forensic biological samples. The key to the success of the system in obtaining results from degraded samples is the primer design yielding small amplicon size (60-125bp) for all 20 markers. The markers included in the InnoTyper® 21 system are bi-allelic, having two possible allelic states (insertion or null) and thus termed INNULs. The markers are short interspersed nuclear elements (SINEs), a category of retrotransposable elements (REs) which are non-coding genomic DNA repeat sequences, or "mobile insertion elements," comprising approximately 40% of the human genome. Alu elements are primate specific SINEs that have reached a copy number in excess of one million in the human genome, which makes these markers highly sensitive and desirable for forensic samples with extremely degraded DNA. Until now however, due to the inherent size difference associated with insertion and no insertion alleles, the use of Alu REs has not been practical for forensic applications. The novel primer design described herein has allowed the development of a multiplexed Alu system yielding fragment sizes amenable to degraded DNA samples, as frequently encountered in missing persons cases or forensic samples such as hair shafts. Although use of Alus in human identity has been studied using single marker amplification and reported before, we report for the first time development and validation of a system with multiplexed RE markers. Studies performed include PCR optimization, species specificity, sensitivity, degradation and inhibition, precision and accuracy, nonprobative samples, mixture, and population database studies. A population study using 592 samples including five populations was performed using InnoTyper 21. The data indicated the random match probability for the combination of these 20 Alu markers was greater than 1 in 3.8 million for the populations studied, indicating the greater statistical power of these autosomal nuclear DNA markers over haplotype systems typically used in such degraded samples. Results demonstrate the system is successful in obtaining results from highly degraded DNA. A sensitivity study performed demonstrated at least 95% recovery of alleles from as low as 50pg of total input DNA, and partial profiles from as low as 25pg. This study has demonstrated that the bi-allelic INNULs in the InnoTyper 21 system provide a sensitivity of detection and a power of discrimination that makes them useful for human identification of extremely degraded samples.


Widespread intersex differentiation across the stickleback genome - The signature of sexually antagonistic selection?
Females and males within a species commonly have distinct reproductive roles, and the associated traits may be under perpetual divergent natural selection between the sexes if their sex-specific control has not yet evolved. Here, we explore whether such sexually antagonistic selection can be detected based on the magnitude of differentiation between the sexes across genome-wide genetic polymorphisms by whole-genome sequencing of large pools of female and male threespine stickleback fish. We find numerous autosomal genome regions exhibiting intersex allele frequency differences beyond the range plausible under pure sampling stochasticity. Alternative sequence alignment strategies rule out that these high-differentiation regions represent sex chromosome segments misassembled into the autosomes. Instead, comparing allele frequencies and sequence read depth between the sexes reveals that regions of high intersex differentiation arise because autosomal chromosome segments got copied into the male-specific sex chromosome (Y), where they acquired new mutations. Because the Y chromosome is missing in the stickleback reference genome, sequence reads derived from DNA copies on the Y chromosome still align to the original homologous regions on the autosomes. We argue that this phenomenon hampers the identification of sexually antagonistic selection within a genome, and can lead to spurious conclusions from population genomic analyses when the underlying samples differ in sex ratios. Because the hemizygous sex chromosome sequence (Y or W) is not represented in most reference genomes, these problems may apply broadly.


Efficacy of a single dose of oral antibiotic given within two hours of birth in preventing watery mouth disease and illthrift in colostrum-deficient lambs.
An antibiotic with a product licence limited to the treatment and control of infectious bacterial enteritis associated with Escherichia coli in piglets was tested for its ability to control watery mouth disease in neonatal lambs. Three groups of lambs were kept in conditions commonly encountered in intensive lambing systems, where high levels of environmental bacterial contamination may be expected. They were allocated at birth to: a control group (group 1) consisting of 18 colostrum-deprived lambs; group 2, consisting of 17 lambs given one feed of colostrum when they were two hours old; and group 3, consisting of 18 colostrum-deprived lambs given spectinomycin orally when they were two hours old. Nine group 1 lambs became diseased and were killed for humane reasons. Blood biochemical changes included hyperglycaemia followed by hypoglycaemia, lactacidaemia, hypoproteinaemia and metabolic acidosis, and postmortem examination of the diseased lambs showed signs consistent with endotoxaemia and a clinical diagnosis of watery mouth disease. Coliforms were isolated from the blood of all group 1 lambs and from half the lambs in groups 2 and 3, but endotoxaemia and watery mouth disease occurred only in group 1 lambs. The results for groups 2 and 3 showed that neither colostrum nor antibiotic at the rates and frequency used prevented bacteraemia, although consecutive samples were positive only on three occasions. Group 3 lambs consistently grew more rapidly than the surviving group 1 lambs and as rapidly as group 2 lambs. There was no evidence that male lambs were more prone to watery mouth disease than female lambs. The results indicated that the antibiotic spectinomycin did not induce endotoxaemia during low-grade bacteraemia and that a single oral dose given within two hours of birth protected colostrum-deprived lambs delivered into a contaminated indoor environment against watery mouth disease.


Incorporation of healthy volunteers data on receptor occupancy into a phase II proof-of-concept trial using a Bayesian dynamic borrowing design.
Receptor occupancy in targeted tissues measures the proportion of receptors occupied by a drug at equilibrium and is sometimes used as a surrogate of drug efficacy to inform dose selection in clinical trials. We propose to incorporate data on receptor occupancy from a phase I study in healthy volunteers into a phase II proof-of-concept study in patients, with the objective of using all the available evidence to make informed decisions. A minimal physiologically based pharmacokinetic modeling is used to model receptor occupancy in healthy volunteers and to predict it in the patients of a phase II proof-of-concept study, taking into account the variability of the population parameters and the specific differences arising from the pathological condition compared to healthy volunteers. Then, given an estimated relationship between receptor occupancy and the clinical endpoint, an informative prior distribution is derived for the clinical endpoint in both the treatment and control arms of the phase II study. These distributions are incorporated into a Bayesian dynamic borrowing design to supplement concurrent phase II trial data. A simulation study in immuno-inflammation demonstrates that the proposed design increases the power of the study while maintaining a type I error at acceptable levels for realistic values of the clinical endpoint.


[The morphological changes in the neural apparatus of the lungs in experimental hypertension].
Histological investigations were conducted in 75 embryos and fetuses with 10- and 20-days term of embryogenesis obtained from 15 pregnant rats with experimental renal hypertension. It was established employing general biological, enzyme histochemical, impregnation and morphometric methods that short-time hypertension of the maternal [correction of material] body produces delay of growth, development and differentiation of nerve cells and their fibers of the respiratory organs. At the same time by the end of pregnancy separate nerve elements were detected with pronounced signs of high organization and differentiation. This should, apparently, be evaluated as a manifestation of compensatory-adaptative properties of the peripheral nervous system to inadequate conditions developing in the process of embryogenesis.


Can injection of adipose stem cells to non-union zone increase bone union? Experimental rat study.
This study aims to evaluate the effects of local adipose stem cell injection on non-union and diabetic non-union of rat femurs. Forty-eight female Wistar albino rats (weighing mean 200 g and aged 8 weeks) were used in this study. The rats were divided into six groups. Group 1 was chosen as a reference for receptor activator of nuclear factor-kappa (κ) B (RANK), receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) genes and no femur osteotomy was performed in this group. Group 2 underwent femur osteotomy, the osteotomy was fixed with a 1.5 mm K-wire as retrograde from the knee joint, and no gap was left in the osteotomy line. In order to induce non-union, femurs underwent osteotomy fixed with K-wires in groups 3, 4, 5 and 6. In addition, the osteotomy line was measured as 1.8 mm gap with electronic calipers and the gap was fixed with U staple. Before osteotomy, streptozocin was injected intraperitoneally at a dose of 60 mg/kg in 0.1 mol/L citrate buffer solution (Ph 4.4) in groups 4 and 6, in order to induce diabetes mellitus. Left femur anteroposterior and lateral X-rays were taken 10 weeks after the operation and the union in group 2 and non-union in groups 3, 4, 5, and 6 were confirmed. To see if injection of adipose stem cells into the non-union site increases bone union, 2 mL 0.9% sodium chloride (NaCl) in groups 3 and 4 and 2×106 adipose stem cell in groups 5 and 6 were locally injected into the non-union area with fluoroscopy. Femur X-rays were taken eight weeks after the injection and all rats were sacrificed. Femurs of rats were removed for histopathological and gene expression evaluation. There were significant differences between the groups injected 0.9% NaCI and adipose stem cells in terms of bone healing according to radiological and histopathological evaluations (p<0.05). No statistically significant difference was observed between the groups in terms of gene expression levels. According to the results of our study, local adipose stem cell injection has positive radiological and histopathological effects in diabetic and non-diabetic femoral non-unions, independently of RANK, RANKL, or OPG gene expression pathways.


Hope and burden among Latino families of adults with schizophrenia.
This study examined hope and family burden among Latino families of individuals with schizophrenia. The sample consisted of 54 family members, one family member per outpatient adult recruited from public mental health programs in a diverse urban community. Hierarchical linear regression analyses were used to test the hypothesis that the family member's increased hope for the patient's future would be associated with decreased family burden beyond effects explained by the patient's length of illness and severity of symptoms. Results supported the study hypothesis. Family hope for the patient's future was associated with four of five types of family burden. Findings point to the prominent role of hope as a source of resilience for Latino families dealing with severe mental illness of a loved one.


Exploring immunoregulatory properties of a phenolic-enriched maple syrup extract through integrated proteomics and in vitro assays.
Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated MSX's ability to regulate inflammatory signaling pathways and modulate inflammatory markers and proteins in a lipopolysaccharide (LPS)-induced peritonitis mouse model. However, MSX's immunoregulatory properties remain unknown. Herein, we investigated MSX's immunoregulatory properties for the first time using an integrated approach, combining data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies in a proteomic analysis of spleen tissue collected from the aforementioned peritonitis mouse model. Additionally, we conducted immune cell activation assays using macrophages and T lymphocytes. The DIA analysis unveiled a distinctive expression pattern involving three proteins-Krt83, Thoc2, and Vps16-which were present in both the control and MSX-treated groups but absent in the LPS-induced model group. Furthermore, proteins Ppih and Dpp9 exhibited significant reductions in the MSX-treated group. Ingenuity pathway analysis indicated that MSX may modulate several critical signaling pathways, exerting a suppressive effect on immune responses in various cell types involved in both innate and adaptive immunity. Our in vitro cell assays supported findings from the proteomics, revealing that MSX significantly reduced the levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated human macrophage cells, as well as the levels of IL-2 in anti-CD3/anti-CD28-induced Jurkat T cells. Taken together, our investigations provide evidence that MSX exerts immune regulatory effects that impact both innate and adaptive immunity, which adds to the data supporting MSX's development as a functional food.


Right atrial volume by cardiovascular magnetic resonance predicts mortality in patients with heart failure with reduced ejection fraction.
Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p<0.001). RAVI (per ml/m2) was an independent predictor of mortality [HR = 1.03 (1.01-1.04), p = 0.001]. RAVI has a greater discriminatory ability than LVEF, left atrial volume index and right ventricular ejection fraction (RVEF) (C-statistic 0.8±0.08 vs 0.55±0.1, 0.62±0.11, 0.68±0.11, respectively, all p<0.02). The addition of RAVI to the MAGGIC score significantly improves risk stratification (integrated discrimination improvement 13%, and category-free net reclassification improvement 73%, both p<0.001). RAVI by CMR is an independent predictor of mortality in patients with HFrEF. The addition of RAVI to MAGGIC score improves mortality risk stratification.


Effects of perceived autonomy support and basic need satisfaction on quality of life in hemodialysis patients.
Despite a growing understanding of health-related quality of life (HRQOL) and its determinants in hemodialysis (HD) patients, little is known about the effects and interrelationships concerning the perception of autonomy support and basic need satisfaction of HD patients on their HRQOL. Based on self-determination theory (SDT), this study examines whether HD patients' perceived autonomy support from health care practitioners (physicians and nurses) relates to the satisfaction of HD patients' basic needs and in turn influences their HRQOL. A questionnaire was administered to 250 Taiwanese HD patients recruited from multiclinical centers and regional hospitals in northern Taiwan. Structural equation modeling (SEM) analysis was conducted to examine the causal relationships between patient perceptions of autonomy support and HRQOL through basic need satisfaction. The empirical results of SEM indicated that the HD patients' perceived autonomy support increased the satisfaction of their basic needs (autonomy, competency, and relatedness), as expected. The higher degree of basic need satisfaction led to higher HRQOL, as measured by physical and mental component scores. Autonomy support from physicians and nurses contributes to improving HD patients' HRQOL through basic need satisfaction. This indicates that staff caring for patients with severe chronic diseases should offer considerable support for patient autonomy.


Ethnic differences in blood pressure and heart rate of Chicago school children.
In 1975-1978, the Chicago Department of Health conducted a screening program that included measurements of blood pressure, heart rate, height, weight, triceps skinfold thickness, and arm circumference, and calculation of body mass index and muscle circumference for non-public school children. Based on data on 4,086 boys and girls aged 5-10 years from the program, this study examined the ethnic differences in blood pressure and heart rate among children of white, black, Latino, and Oriental ethnicity. Mean levels for both systolic and diastolic blood pressure were higher for Oriental and black children than for white and Latino children. These differences were independent of age, height, weight, and skinfold thickness. The black children had a much lower mean heart rate than the other children. A seasonal variation was observed for systolic blood pressure, i.e., with each sex group, the mean systolic blood pressure adjusted for age, skinfold thickness, and height tended to be higher in spring than in fall and winter. (Note-- no child was screened during the summer because of summer break.) With control for season, ethnic differences in systolic blood pressure disappeared, but not the ethnic differences in diastolic blood pressure and heart rate.


Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution.
The three-dimensional structure of the complex between fructose 1,6-bisphosphatase (EC 188.8.131.52) and the physiological inhibitor beta-D-fructose 2,6-bisphosphate (Fru-2,6-P2), an analogue of the substrate (fructose 1,6-bisphosphate), has been refined at 2.6-A resolution to a residual error (R) factor of 0.171. The rms deviations are 0.012 A and 2.88 degrees from ideal geometries of bond lengths and angles, respectively. The Fru-2,6-P2 occupies the active sites of both polypeptides C1 and C2 in the crystallographic asymmetric unit in the space group P3(2)21. The furanose and 6-phosphate of Fru-2,6-P2 are located at the fructose 6-phosphate site established earlier, and the 2-phosphate binds to the OH of Ser-124, the NH3+ of Lys-274, and the backbone NH of Gly-122 and Ser-123. Backbone displacements of 1 A occur for residues from Asp-121 to Asn-125. Model building of substrate alpha-D-Fru-1,6-P2 based on the binding structure of Fru-2,6-P2 in the active site shows interactions of the 1-phosphate with the backbone NH of Ser-123 and Ser-124. In the AMP sites, density peaks attributed to Fru-2,6-P2 are seen in C1 (and C4) but not in C2 (and C3). This minor binding of Fru-2,6-P2 to AMP sites partially explains the synergistic interaction between AMP and Fru-2,6-P2 and the protection of the AMP site from acetylation in the presence of Fru-2,6-P2. In the synergistic interaction between AMP and Fru-2,6-P2, inhibition of catalytic metal binding by the presence of Fru-2,6-P2 at the active site, and propagation of structural changes over some 28 A along beta-strand B3 from residues 121 to 125 in the active site to Lys-112 and Tyr-113 in the AMP site, as well as movement of helices across the interdimeric interfaces, may affect AMP binding and the subsequent R-to-T transition. In addition, occupancy of Fru-2,6-P2 at the AMP sites of C1 and C4 may favor binding of AMP to the remaining unoccupied AMP sites and thus promote the accompanying quaternary conformational changes.


Physiological, biochemical and molecular responses of the potato (Solanum tuberosum L.) plant to moderately elevated temperature.
Although significant work has been undertaken regarding the response of model and crop plants to heat shock during the acclimatory phase, few studies have examined the steady-state response to the mild heat stress encountered in temperate agriculture. In the present work, we therefore exposed tuberizing potato plants to mildly elevated temperatures (30/20 °C, day/night) for up to 5 weeks and compared tuber yield, physiological and biochemical responses, and leaf and tuber metabolomes and transcriptomes with plants grown under optimal conditions (22/16 °C). Growth at elevated temperature reduced tuber yield despite an increase in net foliar photosynthesis. This was associated with major shifts in leaf and tuber metabolite profiles, a significant decrease in leaf glutathione redox state and decreased starch synthesis in tubers. Furthermore, growth at elevated temperature had a profound impact on leaf and tuber transcript expression with large numbers of transcripts displaying a rhythmic oscillation at the higher growth temperature. RT-PCR revealed perturbation in the expression of circadian clock transcripts including StSP6A, previously identified as a tuberization signal. Our data indicate that potato plants grown at moderately elevated temperatures do not exhibit classic symptoms of abiotic stress but that tuber development responds via a diversity of biochemical and molecular signals.


Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor.
The antimicrobial and proinflammatory neutrophil granule protein cathepsin G (CaG) has been reported as a chemoattractant for human phagocytic leukocytes by using a putative G protein coupled receptor. In an effort to identify potential CaG receptor(s), we found that CaG-induced phagocyte migration was specifically attenuated by the bacterial chemotactic peptide fMLP, suggesting these two chemoattractants might share a receptor. In fact, CaG chemoattracts rat basophilic leukemia cells (RBL cells) expressing the high affinity human fMLP receptor FPR, but not parental RBL cells or cells transfected with other chemoattractant receptors. In addition, a specific FPR Ab and a defined FPR antagonist, cyclosporin H, abolished the chemotactic response of phagocytes and FPR-transfected cells to CaG. Furthermore, CaG down-regulated the cell surface expression of FPR in association with receptor internalization. Unlike fMLP, CaG did not induce potent Ca(2+) flux and was a relatively weaker activator of MAPKs through FPR. Yet CaG activated an atypical protein kinase C isozyme, protein kinase Czeta, which was essential for FPR to mediate the chemotactic activity of CaG. Thus, our studies identify CaG as a novel, host-derived chemotactic agonist for FPR and expand the functional scope of this receptor in inflammatory and immune responses.


NK cell response to vaccinia virus is regulated by myeloid-derived suppressor cells.
NK cells are critical for the innate immune control of poxviral infections. Previous studies have shown that NK cells are efficiently activated in response to infection with vaccinia virus (VV), the most studied member of the poxvirus family. However, it remains unknown whether the activation of NK cells in response to VV infection is tightly regulated. In this study, we showed that myeloid-derived suppressor cells (MDSCs) rapidly accumulated at the site of VV infection. In vivo depletion of MDSCs led to enhanced NK cell proliferation, activation, and function in response to VV infection. This was accompanied by an increase in mortality and systemic IFN-γ production. We further demonstrated that the granulocytic-MDSC (G-MDSC) subset was responsible for the suppression on NK cells and that this suppression was mediated by reactive oxygen species. These results indicate that G-MDSCs can negatively regulate NK cell activation and function in response to VV infection and suggest that manipulation of G-MDSCs could represent an attractive strategy for regulating NK cell activities for potential therapeutic benefits.


Rational design of ordered Pd-Pb nanocubes as highly active, selective and durable catalysts for solvent-free benzyl alcohol oxidation.
The selective oxidation of alcohols is an important chemical process with many potential applications in fine-chemical synthesis, however, the catalysts reported so far generally suffer from low activity and poor selectivity. We present here a class of ordered Pd3Pb nanocubes (NCs) with an intermetallic phase and well-defined surface as unique catalysts for selective oxidation of benzyl alcohol to benzaldehyde. The optimized Pd3Pb NCs exhibit both enhanced activity with the turnover frequency of 191 000 h-1 and excellent selectivity up to 91.0%, outperforming the Pd3Pb/Pd NCs and Pd3Pb nanoparticles (NPs) as well as Pd NPs. The Pd3Pb NCs show increased activity in the initially consecutive reaction cycles and do not suffer from distinct deactivation thereafter. X-ray photoelectron spectroscopy reveals that the high ratio of Pd2+ to Pd0 in the surface of Pd-Pb NPs enhances the benzaldehyde productivity, and the electronic modification of the Pd3Pb NCs boosts the benzaldehyde selectivity. Attenuated total reflectance infrared spectra further confirms that the weak benzaldehyde absorption on the Pd3Pb surface results in high selectivity of benzaldehyde.


The functions and regulatory pathways of S100A8/A9 and its receptors in cancers.
Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers.


Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.
We have investigated the genetic evolution of three functionally distinct regions of the equine infectious anemia virus (EIAV) genome (env, rev, and long terminal repeat) during recurring febrile episodes in a pony experimentally infected with a well-characterized reference biological clone designated EIAV(PV). Viral populations present in the plasma of an EIAV(PV)-infected pony during sequential febrile episodes (18, 34, 80, 106, and 337 days postinfection) were amplified from viral RNA, analyzed, and compared to the inoculated strain. The comparison of the viral quasispecies showed that the inoculated EIAV(PV) quasispecies were all represented during the first febrile episode, but entirely replaced at the time of the second febrile episode, and that new predominant quasispecies were associated with each subsequent cycle of disease. One of the more surprising results was the in vivo generation of large deletion (up to 15 amino acids) in the principal neutralizing domain (PND) of gp90 during the third febrile episode. This deletion did not alter the competence for in vitro replication as shown by the analysis of a env chimeric clone with a partially deleted PND and did not altered the fitness of the virus in vivo, since this partially deleted envelope became the major population during the fourth febrile episode. Finally, we showed that the amino acid mutations were not randomly distributed but delineated eight variables regions, V1 to V8, with V3 containing the PND region. These studies provide the first detailed description of the evolution of EIAV genomic quasispecies during persistent infection and reveal new insights into the genetics and potential mechanisms of lentivirus genomic variation.


Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort.
Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth (β = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.


Evaluating adverse drug reactions among HAART patients in a resource-constrained province of South Africa.
The high prevalence of HIV in KwaZulu-Natal Province, South Africa, has greatly increased the demand for antiretroviral therapy (ART), resulting in an exponential increase in the number of patients initiated on highly active antiretroviral treatment (HAART). However, little information about adverse drug reactions in these patients was forthcoming from public health facilities in KwaZulu-Natal. A compulsory system of reporting adverse drug reactions was established among patients attending accredited ART sites, with minimal resource requirements. The study sought to evaluate the adverse drug reactions reported through the new compulsory system. A retrospective audit was performed on the reporting forms received during the first year of the new system, pertaining to all patients on HAART who had experienced an adverse drug reaction that resulted in a request for a change in antiretroviral (ARV) drug or regimen. The forms for documenting adverse drug reactions were completed by prescribers who would confirm the event or reaction by specifying the diagnosis as well as the relevant clinical and laboratory values. In total, 3 923 forms, submitted between 1 May 2007 and 31 May 2008, were available for audit. Adverse drug reactions were documented in 78.7% of the reports and 74% of the patients that presented with an adverse event were females. Of the forms recording a serious adverse drug reaction, 84.7% pertained to patients taking the three-drug combination stavudine, lamivudine and either efavirenz or nevirapine. Of those reports, stavudine was implicated as the possible causative agent of an adverse drug reaction in 93% of the cases. In 73.6% of the total reports the proposed new regimen was zidovudine, lamivudine and efavirenz or nevirapine. The compulsory system of reporting greatly improved the reporting of adverse drug reactions associated with HAART among patients in the province. This system may be similarly implemented in other low-resourced settings to actively encourage the reporting of adverse drug reactions associated with ARV use.


Comprehensive characterization of ethoxyquin transformation products in fish feed by traveling-wave ion mobility spectrometry coupled to quadrupole time-of-flight mass spectrometry.
Feed additives are typically used in intensive farming production over long periods, and hence, they can accumulate in farmed animal tissues. Concerns regarding the use of ethoxyquin as an antioxidant feed additive, have recently arisen due to its potential conversion into a series of transformation products (TPs). The aim of this work was to characterize the TPs of ethoxyquin in fish feed by a novel approach based on the use of traveling-wave ion mobility spectrometry (TWIMS) coupled to high-resolution quadrupole time-of-flight mass spectrometry (QTOFMS). First, ethoxyquin was oxidized under controlled conditions and the generated TPs were added to a comprehensive database. Atlantic salmon feeds were then screened for ethoxyquin TPs using both targeted and untargeted approaches. Twenty-seven TPs were tentatively identified during the oxidation experiments, fifteen of them also being present in the feed samples. In addition, ten other potential TPs were detected in fish feed following the untargeted approach. Thirty-one of these TPs have been reported for the first time in this work through the oxidation experiments and the feed samples. Therefore, this study provides valuable information on the oxidative fate of ethoxyquin in feed, which can be used for future evaluations of potential risk related to this additive.


A complete method for assessing the effectiveness of eyewitness identification procedures: Expected information gain.
We present a method for measuring the efficacy of eyewitness identification procedures by applying fundamental principles of information theory. The resulting measure evaluates the expected information gain (EIG) for an identification attempt, a single value that summarizes an identification procedure's overall potential for reducing uncertainty about guilt or innocence across all possible witness responses. In a series of demonstrations, we show that EIG often disagrees with existing measures (e.g., diagnosticity ratios or area under the receiver operating characteristic) about the relative effectiveness of different identification procedures. Each demonstration is designed to highlight key distinctions between existing measures and EIG. An overarching theme is that EIG provides a complete measure of evidentiary value, in the sense that it factors in all aspects of identification performance. Collectively, these demonstrations show that EIG has substantial potential to inspire new discoveries in eyewitness research and provide a new perspective on policy recommendations for the use of identifications in real investigations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Characterization of extended-spectrum beta-lactamase-producing isolates of Haemophilus parainfluenzae.
To characterize the beta-lactam resistance mechanisms of two clinical isolates of cefotaxime-resistant Haemophilus parainfluenzae recovered from patients in South Africa. The relatedness of isolates and plasmids was assessed using PFGE and restriction enzyme analysis, respectively. Plasmid-mediated and chromosomally integrated bla(TEM) genes and ftsI genes were sequenced, and the plasmid-mediated bla(TEM-15) was used to transform a range of control organisms. The two isolates were found to be unique according to PFGE, but had an identical 3.7 kb plasmid encoding a TEM-15 beta-lactamase. Both isolates also had substitutions in penicillin binding protein 3 (PBP3) consistent with substitutions known to exist in beta-lactamase-negative ampicillin-resistant (BLNAR) strains of Haemophilus influenzae. The cefotaxime MICs for control strains of H. influenzae, H. parainfluenzae and BLNAR H. influenzae transformed with the plasmid-mediated bla(TEM-15) were 1.0, 1.0 and 4.0 mg/L, respectively, compared with 16.0 and 8.0 mg/L, respectively, for the two parent H. parainfluenzae. The high-level cefotaxime resistance in the H. parainfluenzae isolates was due to a combination of a plasmid-mediated TEM-15 extended-spectrum beta-lactamase with altered PBP3 probably contributing. Other contributing resistance mechanisms could not be excluded.


In vitro antioxidant and antimalarial activities of leaves, pods and bark extracts of Acacia nilotica (L.) Del.
The emergence of drug resistant malaria is threatening our ability to treat and control malaria in the Southeast Asian region. There is an urgent need to develop novel and chemically diverse antimalarial drugs. This study aimed at evaluating the antimalarial and antioxidant potentials of Acacia nilotica plant extracts. The antioxidant activities of leaves, pods and bark extracts were determined by standard antioxidant assays; reducing power capacity, % lipid peroxidation inhibition and ferric reducing antioxidant power assay. The antimalarial activities of plant extracts against Plasmodium falciparum parasites were determined by the 48 h schizont maturation inhibition assay. Further confirmation of schizonticide activity of extracts was made by extending the incubation period up to 96 h after removing the plant extract residues from parasites culture. Inhibition assays were analyzed by dose-response modelling. In all antioxidant assays, leaves of A. nilotica showed higher antioxidant activity than pods and bark. Antimalarial IC50 values of leaves, pods and bark extracts were 1.29, 4.16 and 4.28 μg/ml respectively, in the 48 h maturation assay. The IC50 values determined for leaves, pods and bark extracts were 3.72, 5.41 and 5.32 μg/ml respectively, after 96 h of incubation. All extracts inhibited the development of mature schizont, indicating schizonticide activity against P. falciparum. A. nilotica extracts showed promising antimalarial and antioxidant effects. However, further investigation is needed to isolate and identify the active components responsible for the antimalarial and antioxidant effects.


Do small changes in rotation affect measurements of lower extremity limb alignment?
The alignment of the lower extremity has important implications in the development of knee arthritis. The effect of incremental rotations of the limb on common parameters of alignment has not been studied. The purpose of the study was to (1) determine the standardized neutral position measurements of alignment and (2) determine the effect of rotation on commonly used measurements of alignment. Eighty-seven full length CT angiography studies (49 males and 38 females, average age 66 years old) were included. Three-dimensional models were created using a rendering software program and placed on a virtual plane. An image of the extremity was obtained. Thirty scans were randomly selected, and those models were rotated in 3° intervals around the longitudinal axis and additional images were obtained. In the neutral position, the mechanical lateral distal femoral articular angle (mLDFA) was 85.6 ± 2.3°, medial proximal tibial angle (MPTA) was 86.1 ± 2.8°, and mechanical tibiofemoral angle (mTFA) was -0.7 ± 3.1°. Females had a more valgus alignment with a mTFA of 0.5 ± 2.9° while males had a more varus alignment with a mTFA of -1.7 ± 2.9°. The anatomic tibiofemoral angle (aTFA) was 4.8 ± 2.6°, the anatomic lateral distal femoral angle (aLDFA) measured 80.2 ± 2.2°, and the anatomical-mechanical angle (AMA) was 5.4 ± 0.7°. The prevalence of constitutional varus was 18%. The effect of rotation on the rotated scans led to statistically significant differences relative to the 0° measurement for all measurements. These effects may be small, and their clinical importance is unknown. This study provides new information on standardized measures of lower extremity alignment and the relationship between discreet axial rotations of the entire lower extremity and these parameters.


Care for older adults with disabilities in Long Term Care Facility.
to analyze the constitution of care offered to older adults with disabilities, from Long Term Care Facility professionals' perspective. this is a discourse analysis based on the post-structuralist framework. Participants in this study are professionals involved in the care for older adults, totaling 14 respondents, 13 women and one man. from professionals' perspective, there is a fine line between caring for older adults with disabilities and maintaining their autonomy. Care in which autonomy is restricted predisposes older adults to a process of dependency. caring for older adults with disabilities constitutes the challenge between caring and maintaining independence. Thus, older adult-centered care should be taken as a premise so that their individualities are respected.


Symptoms and cholinesterase activity among rural residents living near cotton fields in Nicaragua.
To explore whether symptoms resulted from pesticide spray drift on residentially exposed populations in rural Nicaragua. 100 residents, each 10 years of age or older, were randomly selected from a Nicaraguan community surrounded by actively sprayed cotton fields (the exposed community) and from a socioeconomically similar community far from agricultural spraying (the control community). Subjects working with pesticides were excluded, and the study was conducted at the end of the 1990 cotton spraying season (August-December). Demographic information, exposure questions, and prevalence of 11 acute symptoms and 17 chronic symptoms were gathered from a structured interview. Finger stick erythrocyte cholinesterase (AChE) was measured with a portable colorimeter. Acute symptoms were grouped according to their previously known associations with cholinesterase (ChE) inhibitors into four ordinal categories (asymptomatic, non-specific, possible, probable). Residents from the exposed community were significantly more likely to report recently sighting a spray plane near their community, exposure to pesticide from drift, crossing recently sprayed fields, eating home grown food, and feeling ill after drift exposure. The mean AChE value was significantly lower for residents of the exposed community (4.9 v 5.3 IU/dl). The proportion of subjects complaining of one or more chronic or acute symptoms was significantly higher for the exposed community (87%) than for the controls (53%). Odds ratios for residents in the exposed community, by symptom categories, were non-specific 1.6 (95% confidence interval (95% CI) 0-8 to 3.2), possible 4.1 (95% CI 1.7 to 10.2), and probable 9.93 (95% CI 2-9 to 34.4). These findings indicate a strong association between exposure to aerial pesticides and symptoms. This study should be replicated with more quantitative exposure measures, for if confirmed, the results have relevance for millions in rural communities worldwide.


Effects of the Mean Amplitude of Glycemic Excursions and Vascular Endothelial Dysfunction on Cardiovascular Events in Nondiabetic Patients With Coronary Artery Disease.
Mean amplitude of glycemic excursion (MAGE) is commonly used to gauge the degree of glucose level fluctuations. MAGE plays a significant role in vascular endothelial dysfunction and cardiovascular events in patients with diabetes mellitus (DM), but its significance is not clear in non-DM patients. Thus, we examined the impact of MAGE and vascular endothelial dysfunction on clinical outcomes in non-DM patients with coronary artery disease. We followed non-DM patients (n=65) for 12 months who underwent percutaneous coronary intervention and assessed the relationship among MAGE, reactive hyperemia index (RHI) measured by reactive hyperemia peripheral arterial tonometry as endothelial function, and cardiovascular events. Cardiovascular events analyzed were cardiovascular death, myocardial infarction, unstable angina, and revascularizations. Compared with patients with MAGE <65 mg/dL (normal glycemic excursions), the group with MAGE ≥65 mg/dL (high glycemic excursions) had significantly higher high-sensitivity C-reactive protein (0.10±0.11 mg/dL versus 0.18±0.13 mg/dL, P=0.006) and lower RHI (0.64±0.21 versus 0.51±0.22, P=0.035). The multivariable analysis identified high MAGE and low RHI (≤0.56) as risk factors associated with cardiovascular events (hazard ratio, 5.6; 95% RI, 1.72-18.4 [P=0.004] versus hazard ratio, 4.5; 95% RI, 1.37-14.9 [P=0.013]). When the prognosis was classified by combination with MAGE and RHI, the incidence of cardiovascular events was 46.7% (high MAGE+low RHI), 26.7% (high MAGE+high RHI), 20.0% (low MAGE+low RHI), and 6.6% (low MAGE+high RHI) in descending order (P=0.014). Receiver operating characteristic curve analysis revealed that MAGE, RHI, and MAGE+RHI were each associated with cardiovascular events (area under the curve 0.780, 0.727, and 0.796, respectively). MAGE was associated with cardiovascular events in non-DM patients with coronary artery disease. Furthermore, the combination with MAGE and RHI was useful for further subdivision of the risk of cardiovascular events.


Circulating tumor cells as a new predictive and prognostic factor in patients with small cell lung cancer.
Background: Small cell lung cancer (SCLC) is the most malignant type of lung cancer characterized by rapid progression, early metastasis and recurrence. In recent years, circulating tumor cells (CTCs) were found to play an important role in tumor invasion, metastasis, recurrence and prognosis. Methods: CTCs were detected in 138 patients with newly diagnosed SCLC from January 2012 to December 2018. Nomogram prediction models were constructed based on prognostic factors screened by multivariate Cox regression analysis and the risk stratification of SCLC patients were performed on basis of nomogram points. A total of 108 patients from January 2012 to December 2016 were assigned to a training group, and 30 patients from January 2017 to December 2018 were included into the validation group for nomogram analysis. This study was approved by ethics committee of Guangzhou First People's Hospital and all subjects provided informed consent. Results: The number of CTCs was associated with age, lymph node metastasis (N), distant metastasis (M), TNM staging, and NSE. The high number of CTC predicted adverse prognosis, and the AUC of time-dependent ROC curve was all high than 0.5. In the training group, after multivariate COX regression screening, the factors in the median survival time (MST) and overall survival (OS) nomogram prediction models were age, TNM, CTC, NSE and treatment mode. The C-index of the nomograms in internal validation for MST and OS was 0.813 and in external validation for MST and OS were 0.885. The AUC of ROC curves for nomogram were high than 0.5. Finally, risk stratification could be effectively performed on the basis of nomogram points. Conclusions: CTC can be served as a predictive and prognostic factor for SCLC, and the nomogram models constructed by CTC and multiple clinical parameters can comprehensively predict the prognosis of SCLC patients and perform risk stratification.


Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection.
The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States. The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively. Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.


Direct amide synthesis via Ni-mediated aminocarbonylation of arylboronic acids with CO and nitroarenes.
Herein we describe an alternative and unconventional approach of an aminocarbonylation reaction to access aryl amides from readily available and low-cost arylboronic acids and nitroarenes. Nickel metal can serve as both reductant and catalyst in this direct aminocarbonylation. This protocol exhibits a good functional group compatibility and allows a variety of aryl amides to be synthesized, including several drug-like molecules.


Pulmonary embolism in patients with CKD and ESRD.
CKD and ESRD are growing burdens. It is unclear whether these conditions affect pulmonary embolism (PE) risk, given that they affect both procoagulant and anticoagulant factors. This study examined the frequency and associated outcomes of PE in CKD and ESRD. The Healthcare Cost and Utilization Project's Nationwide Inpatient Sample was used to estimate the frequency and outcomes of PE in adults with CKD and ESRD. Hospitalizations for the principal diagnosis of PE and presence of CKD or ESRD were identified using International Classification of Diseases, Ninth Revision codes. Data from the annual US Census and US Renal Data System reports were used to calculate the number of adults with CKD, ESRD, and normal kidney function (NKF) as well as the annual incidence of PE in each group. Logistic regression modeling was used to compare in-hospital mortality among persons admitted for PE who had ESRD or CKD to those without these conditions. The annual frequency of PE was 527 per 100,000, 204 per 100,000, and 66 per 100,000 persons with ESRD, CKD, and NKF, respectively. In-hospital mortality was higher for persons with ESRD and CKD (P<0.001) compared with persons with NKF. Median length of stay was longer by 1 day in CKD and 2 days in ESRD than among those with NKF. Persons with CKD and ESRD are more likely to have PE than persons with NKF. Once they have PE, they are more likely to die in the hospital.


A Comparison of the Effects of Short-Term Plyometric and Resistance Training on Lower-Body Muscular Performance.
Whitehead, MT, Scheett, TP, McGuigan, MR, and Martin, AV. A comparison of the effects of short-term plyometric and resistance training on lower-body muscular performance. J Strength Cond Res 32(10): 2743-2749, 2018-The purpose of this study was to compare effects of short-term plyometric and resistance training on lower-body muscular performance. A convenience sample of 30 male subjects aged 21.3 ± 1.8 years (height, 177.3 ± 9.4 cm; mass, 80.0 ± 2.6 kg; body fat, 16.1 ± 1.2%) participated in this investigation. Participants were grouped, and they participated in progressive plyometric (PLT) or resistance training (SRT) twice per week for 8 consecutive weeks or a control (CNT) group that did not participate in any training. Performance tests were administered before and after the training period, and it included measures of high-speed muscular strength (standing long jump, vertical jump), low-speed muscular strength (1-repetition maximal back squat), running speed (20-m sprint), and running agility (505 agility test). Analysis of variance followed by post hoc analyses was performed to determine significant differences between the groups. Significance set at p ≤ 0.05 for all analyses. Significant improvements were observed in the PLT group for standing long jump, vertical jump, and 1-repetition maximal back squat compared with the CNT group and for vertical jump as compared with the SRT group. Significant improvements were observed in the SRT group 1-repetition maximal back squat compared with the CNT group. There were no differences observed between any of the groups for the 20-m sprint or the 505 agility test after the training. These data indicate that 8 weeks of progressive plyometric training results in improvements in parameters of high-speed and low-speed muscular strength with no appreciable change in speed or agility. Additionally, the improvement in low-speed muscular strength observed from 8 weeks of progressive plyometric training was comparable to the results observed from 8 weeks of progressive strength training.


Quality of clinical practice guidelines for gestational and congenital toxoplasmosis: A systematic review of the literature.
To evaluate the methodological quality and transparency of the clinical practice guidelines (CPGs) for the prevention, diagnosis, and treatment of gestational and congenital toxoplasmosis (CT). Systematic review of the literature on gestational and CT CPGs conducted in the MEDLINE, Embase, TripDatabase, Biblioteca Virtual en Salud databases and extensive manual searches in 19 CPG repositories. The characteristics of each of the guidelines were extracted using My AGREE PLUS on-line. Three reviewers assessed overall quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The combined systematic review found 8651 citations. Of them 46 full texts were reviewed, and eight documents were finally included: four toxoplasmosis CPGs, three prenatal care CPGs that included recommendations on toxoplasmosis, and one pregnancy infection guideline that also included recommendations on toxoplasmosis. The AGREE II domains found to have the highest scores were 'clarity of presentation' (85%; [37%-100%]), followed by 'scope and purpose' (73%; [33%-98%]), and 'editorial independence' (51%; [3%-94%]); the domains with the lowest scores were 'rigour of development' (36%; [11%-79%]), 'stakeholder involvement' (34%; [24%-85%]), and 'applicability' (17%; [6%-83%]). The Colombian and Spanish-Agencia de Evaluación de Tecnologías Sanitarias de Andalucía (AETSA) CPGs had the highest global AGREE II scores. Absolute interrater agreement was good to excellent. Substantial quality variation was found among CPGs, which provided recommendations in accordance with the context of the disease in the corresponding country or region. Only two of the CPGs appraised obtained a good score and are classified as 'recommended'.


Patellofemoral pain syndrome.
Patellofemoral pain (PFP) syndrome is a frequently encountered overuse disorder that involves the patellofemoral region and often presents as anterior knee pain. PFP can be difficult to diagnose. Not only do the etiology, diagnosis, and treatment remain challenging, but the terminology used to describe PFP is used inconsistently and can be confusing. Patellofemoral pain syndrome (PFPS) seems to be multifactorial, resulting from a complex interaction among intrinsic anatomic and external training factors. Although clinicians frequently make the diagnosis of PFPS, no consensus exists about its etiology or the factors most responsible for causing pain. This article discusses the pathophysiology, diagnosis, and management of PFP.


Disentangling the Relative Roles of Vertical Transmission, Subsequent Colonizations, and Diet on Cockroach Microbiome Assembly.
A multitude of factors affect the assemblies of complex microbial communities associated with animal hosts, with implications for community flexibility, resilience, and long-term stability; however, their relative effects have rarely been deduced. Here, we use a tractable lab model to quantify the relative and combined effects of parental transmission (egg case microbiome present/reduced), gut inocula (cockroach versus termite gut provisioned), and varying diets (matched or unmatched with gut inoculum source) on gut microbiota structure of hatchlings of the omnivorous cockroach Shelfordella lateralis using 16S rRNA gene (rDNA) amplicon sequencing. We show that the presence of a preexisting bacterial community via vertical transmission of microbes on egg cases reduces subsequent microbial invasion, suggesting priority effects that allow initial colonizers to take a strong hold and which stabilize the microbiome. However, subsequent inoculation sources more strongly affect ultimate community composition and their ecological networks, with distinct host-taxon-of-origin effects on which bacteria establish. While this is so, communities respond flexibly to specific diets in ways that consequently impact predicted community functions. In conclusion, our findings suggest that inoculations drive communities toward different stable states depending on colonization and extinction events, through ecological host-microbe relations and interactions with other gut bacteria, while diet in parallel shapes the functional capabilities of these microbiomes. These effects may lead to consistent microbial communities that maximize the extended phenotype that the microbiota provides the host, particularly if microbes spend most of their lives in host-associated environments.IMPORTANCE When host fitness is dependent on gut microbiota, microbial community flexibility and reproducibility enhance host fitness by allowing fine-tuned environmental tracking and sufficient stability for host traits to evolve. Our findings lend support to the importance of vertically transmitted early-life microbiota as stabilizers, through interactions with potential colonizers, which may contribute to ensuring that the microbiota aligns within host fitness-enhancing parameters. Subsequent colonizations are driven by microbial composition of the sources available, and we confirm that host-taxon-of-origin affects stable subsequent communities, while communities at the same time retain sufficient flexibility to shift in response to available diets. Microbiome structure is thus the result of the relative impact and combined effects of inocula and fluctuations driven by environment-specific microbial sources and digestive needs. These affect short-term community structure on an ecological time scale but could ultimately shape host species specificities in microbiomes across evolutionary time, if environmental conditions prevail.


Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics.
Cirrhosis is the result of chronic liver disease that causes scarring and dysfunction of the liver. The disease is a common concomitant condition resulting from sustained exposure to alcohol. Heavy alcohol use results in brain damage that is generally more severe in cirrhotic compared with noncirrhotic alcoholics. We examined, at the cellular level, gene expression in the frontal cortex of cirrhotic alcoholics. Gene expression profiles were compared between cirrhotic and noncirrhotic alcoholics using approximately 47,000 element cDNA microarrays. Widespread differences in transcriptome patterns were observed in cirrhotic compared with noncirrhotic alcoholics and these differences in gene expression accurately distinguished cirrhotic from noncirrhotic alcoholics. Functionally related groups of genes were identified that are involved in cell adhesion, mitochondrial function, synaptic transmission, apoptosis, and cell proliferation. Both astrocytes and neuronal cells were affected at the transcriptional level. The regulated genes are involved in neurite growth, neuronal cell adhesion, synaptic vesicle release, and postsynaptic neurotransmission. These changes in the transcriptome likely contribute to the more severe brain dysfunction in cirrhotic alcoholics.


PAH extraction and estimation of plasma flow in diseased human kidneys.
We have analyzed the efficiency with which p-amino-hippuric acid (PAH) is extracted (EPAH) by patients with healthy kidneys (n = 13) or kidneys damaged by chronic cyclosporin nephropathy (n = 21) or primary glomerulopathy (n = 12); respective values (mean +/- SE) for EPAH were 0.87 +/- 0.03, 0.77 +/- 0.03, and 0.69 +/- 0.04. Judged by a 131I-hippuran-to-PAH clearance ratio of 0.75 +/- 0.05, extraction ratio of hippuran was less efficient than EPAH in three glomerulopathic patients. A direct relationship was defined between EPAH and glomerular filtration rate (GFR) (r = 0.54) or calculated efferent oncotic pressure (IIE; r = 0.41, P less than 0.01). Curve fitting by means of quadratic spline functions revealed GFR and IIE to be additive in predicting EPAH (R2 = 0.45). Linear model prediction methods and a sample reuse technique failed to predict EPAH reliably from GFR and preglomerular oncotic pressure (IIA); however, 95% prediction intervals exceed 0.30 EPAH units in width. We conclude that oncotic pressure (presumably reflecting albumin concentration) along with GFR is predictive of EPAH depression in humans with chronic renal disease. However, even sophisticated curve-fitting techniques are too imprecise for accurate prediction of EPAH in a given individual. We submit that renal venous sampling to determine EPAH continues to be necessary for the accurate determination of the rate of plasma flow in the injured human kidney.


Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome.
Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months. These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.


Early postoperative prediction of the risk of distant metastases in medullary thyroid cancer.
The purpose of this study was to develop and validate a nomogram for estimating the risk of distant metastases (DM) in the early postoperative phase of medullary thyroid cancer (MTC). We retrospectively reviewed cases of patients diagnosed with MTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2007 to 2017. In addition, we gathered data on patients who diagnosed as MTC at Department of Thyroid Surgery in the First Hospital of Jilin University between 2009 and 2021. Four machine learning algorithms were used for modeling, including random forest classifier (RFC), gradient boosting decision tree (GBDT), logistic regression (LR), and support vector machine (SVM). The optimal model was selected based on accuracy, recall, specificity, receiver operating characteristic curve (ROC), and area under curve (AUC). After that, the Hosmer-Lemeshow goodness-of-fit test, the brier score (BS) and calibration curve were used for validation of the best model, which allowed us to measure the discrepancy between the projected value and the actual value. Through feature selection, we finally clarified that the following four features are associated with distant metastases of MTC, which are age, surgery, primary tumor (T) and nodes (N). The AUC values of the four models in the internal test set were as follows: random forest: 0.8786 (95% CI, 0.8070-0.9503), GBDT: 0.8402 (95% CI, 0.7606-0.9199), logistic regression: 0.8670(95%CI,0.7927-0.9413), and SVM: 0.8673 (95% CI, 0.7931-0.9415). As can be shown, there was no statistically significant difference in their AUC values. The highest AUC value of the four models were chosen as the best model since. The model was evaluated on the internal test set, and the accuracy was 0.84, recall was 0.76, and specificity was 0.87. The ROC curve was drawn, and the AUC was 0.8786 (95% CI, 0.8070-0.9503), which was higher than the other three models. The model was visualized using the nomogram and its net benefit was shown in both the Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC). Proposed model had good discrimination ability and could preliminarily screen high-risk patients for DM in the early postoperative period.


[Bifurcation coronary stenting guided by intravascular diagnostic tools].
Results of coronary bifurcation stenting guided by intravascular diagnostic tools were searched. 85 patients took part in the study, there were generated two groups. In the research group intravascular ultrasound of main vessel has revealed stent malapposition in 97.6%. Fractional flow reserve of jailed side branch ostium is less then 0.75 in 7.1% only, despite of the average 78 +/- 4% narrowing. Severe cardiac events in research group during long-term clinical follow-up were better in research group: 6.9% vs 32.5% (p < 0.05).


Anomalous water molecules and mechanistic effects of water nanotube clusters confined to molecular porous crystals.
The movement of water molecules in the limited space present within nanoscale regions, which is different from the molecular motion of bulk water, is significantly affected by strong interfacial interactions with the surrounding outer walls. Hence, most of the water molecules that are confined to nanochannel spaces having widths less than ca. 2 nm can generally be classified together as "structural water". Since the motions of such water molecules are limited by interfacial interactions with the outer wall, the nature of structural water, which is strongly influenced by the interactions, will have different characteristics from normal water. For our investigations on the characteristics of structural water, we have developed a nanoporous crystal with a diameter of ca. 1.6 nm; it was constructed from 1-D hydrophilic channels by self-organization of the designed molecules. A tubelike three-layered water cluster, called a water nanotube (WNT), is formed in each internal channel space and is regulated by H-bonds with the outer wall. The WNT undergoes a glass transition (T(g) = 107 K) and behaves as a liquid; it freezes at 234 K and changes into an icelike nanotube cluster. In this study, the structure of the WNT is investigated through neutron structure analysis, and it is observed to stabilize by a mechanistic anchor effect of structural water. Furthermore, from neutron-scattering experiments, it is seen that a few water molecules around the center of the WNT move approximately with the same diffusion constant as those in bulk water; however, the residence time and average jump length are longer, despite the restrictions imposed by the H-bonding with structural water. The behavior of mobile water within a WNT is investigated; this can be used to elucidate the mechanism for the effect of structural water on vital functions on the cell surface.


Health inequities: the need for action by schools of medicine.
It is well recognised that marked inequalities in mortality and morbidity exist between populations particularly those in lower socio-economic groups, including Indigenous and some ethnic minorities. Academic medicine has not yet articulated a clear stance on reducing health inequity within communities. To develop criteria that medical schools can implement to reduce health inequity. These criteria will enable the performance of a medical school's commitment to health equity to be measured. We suggest that the contribution to lessening health inequity should be seen as an integral and important role of undergraduate medical education and the academic institutions that provide such programs. Five strategies aimed at increasing the commitment of medical and other undergraduate health students to work with disadvantaged groups to improve their health are described. They include student selection to increase representativeness of students and importantly, support for retention and academic success; undergraduate curriculum, both core and elective, to address inequality and provide skills necessary to implement change in a range of areas that impact on health; academic physicians modelling the above by actively working in and for disadvantaged groups; developing centres of excellence carrying out research in health inequity, particularly intervention rather than solely descriptive research and creating high status academic appointments in key designated positions addressing inequity. Schools of Medicine could be rated on their action on these criteria so that benchmarking across institutions could occur.


Is there such thing as a parasite free lunch? The direct and indirect consequences of eating invasive prey.
As the number of invasive species increases globally, more and more native predators are reported to shift their diet toward invasive prey. The consequences of such diet shifts for the health of populations of native predators are poorly studied, but diet shifts are expected to have important parasitological and immunological consequences, ultimately affecting predator fitness. We reviewed evidence that diet shifts from native to invasive prey can alter parasite exposure directly and also indirectly affect immune functions via changes in condition and contaminant exposure. We highlight relevant conceptual and methodological tools that should be used for the design of experiments aimed at exploring important links between invasive prey and parasitism, contaminants and fitness of their native predators.


Calculation of third to eighth virial coefficients of hard lenses and hard, oblate ellipsoids of revolution employing an efficient algorithm.
We provide third to eighth virial coefficients of oblate, hard ellipsoids of revolution and hard lenses in dependence on their aspect ratio ν. Employing an algorithm optimized for hard anisotropic shapes, highly accurate data are accessible with comparatively small numerical effort. For both geometries, reduced virial coefficients B[over ̃]_{i}(ν)=B_{i}(ν)/B_{2}^{i-1}(ν) are in first approximation proportional to the inverse excess contribution α^{-1} of their excluded volume. The latter quantity is directly accessible from second virial coefficients and analytically known for convex bodies.


The influence of Gd-DOTA conjugating ratios to PLGA-PEG micelles encapsulated IR-1061 on bimodal over-1000 nm near-infrared fluorescence and magnetic resonance imaging.
Multimodal imaging can provide multidimensional information for understanding concealed microstructures or bioprocesses in biological objects. The combination of over-1000 nm near-infrared (OTN-NIR) fluorescence imaging and magnetic resonance (MR) imaging is promising in providing high sensitivity and structural information of lesions. This combination can be facilitated by the development of an imaging probe. The OTN-NIR and MR bimodal fluorescence probes reported to date primarily involve ceramic particles for fluorescence and MRI contrast enhancement effect. In this study, we designed a new bimodal OTN-NIR/MR imaging probe from organic components including an OTN-NIR fluorescent organic dye (IR-1061) encapsulated in the core of a micelle composed of poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer (PLGA-PEG). For the MRI contrast, gadobutrol (Gd-DOTA) was introduced at the end of the PEG chain at various ratios. Thereafter, the OTN-NIR fluorescence and MR bimodal imaging probes of ca. 20 nm in size were successfully prepared and applied in mouse imaging. The probe exhibited absorption and emission in the OTN-NIR, and T1 contrast enhancement effects on MRI. Moreover, it demonstrated bright OTN-NIR fluorescence and MRI contrast enhancement to depict veins and observe the organs in live mice. The imaging results revealed that the Gd-DOTA introduction ratio is of great importance for controlling the biological response of the probe without reducing the contrast enhancement effect.


The organizing role of Wnt signaling pathway during arthropod posterior growth.
Wnt signaling pathways are recognized for having major roles in tissue patterning and cell proliferation. In the last years, remarkable progress has been made in elucidating the molecular and cellular mechanisms that underlie sequential segmentation and axial elongation in various arthropods, and the canonical Wnt pathway has emerged as an essential factor in these processes. Here we review, with a comparative perspective, the current evidence concerning the participation of this pathway during posterior growth, its degree of conservation among the different subphyla within Arthropoda and its relationship with the rest of the gene regulatory network involved. Furthermore, we discuss how this signaling pathway could regulate segmentation to establish this repetitive pattern and, at the same time, probably modulate different cellular processes precisely coupled to axial elongation. Based on the information collected, we suggest that this pathway plays an organizing role in the formation of the body segments through the regulation of the dynamic expression of segmentation genes, via controlling the caudal gene, at the posterior region of the embryo/larva, that is necessary for the correct sequential formation of body segments in most arthropods and possibly in their common segmented ancestor. On the other hand, there is insufficient evidence to link this pathway to axial elongation by controlling its main cellular processes, such as convergent extension and cell proliferation. However, conclusions are premature until more studies incorporating diverse arthropods are carried out.


[Performance of nutritional education programmes to prevent obesity in children through a pilot study in Soria].
Spain has one of the highest rates of childhood obesity in Europe. The Spanish authorities of health have launched some strategies, which among others, includes activities to develop healthier dietary habits in children. The aim of the present study has been to assess the effectiveness of the nutritional education programmes undertaken to prevent obesity in children through a pilot study in Soria. This has been evaluated through the comparative study of adherence to the Mediterranean Diet and anthropometric parameters between two samples of same age schoolchildren at an interval of 10 years. Adherence to the Mediterranean diet and BMI was evaluated in two occasional samples of pupils aged between 6 and 9 years, who were attended to 5 public Schools in Soria, during two academic years 1998/ 99 (n=119) and 2008/09 (n=231). Adherence to the Mediterranean diet was evaluated by the KidMed index. There were no differences in KidMed score between sexes within the same sample. However, there were a significant differences (p<0.0001) in total KidMed socore between the 2008/09 and 1998/99 schoolchildren. The mean BMIs were similar for the boys and girls of the same course, while it was significantly lower (p<0.05) in 2008/09 school children. The Kidmed score was negatively associated with BMI (r=-0.133, p<0.05). The proportion of childhood that showed an upper-middle degree of adherence to the Mediterranean diet patterns was higher among 2008-09 pupils. These results suggests that activities coordinated from different agencies in Spain, may be a useful tool for promotion of healthy eating habits in children.


[Simultaneous determination of pesticide residues in agricultural products by LC-MS/MS].
A method for the simultaneous determination of multiple pesticide residues in agricultural products was developed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The sample was extracted with acetonitrile. Co-extractives were removed by GPC/graphitized carbon column SPE, and silica gel/PSA cartridge column SPE. Pesticides in the test solution were determined by LC-MS/MS using scheduled MRM. Recoveries of 124 pesticides from spinach, brown rice, soybean, orange and tomato were tested at the level of 0.1 µg/g, and those of 121 pesticides ranged from 70 to 120% (RSD≤15%). Pesticide residues in 239 agricultural products were investigated by this method, and residues of 49 pesticides were detected in 98 agricultural products.


Spatial generalization from learning dynamics of reaching movements.
When subjects practice reaching movements in a force field, they learn a new sensorimotor map that associates desired trajectories to motor commands. The map is formed in the brain with elements that allow for generalization beyond the region of training. We quantified spatial generalization properties of these elements by training in one extreme of the reachable space and testing near another. Training resulted in rotations in the preferred direction (PD) of activation of some arm muscles. We designed force fields that maintained a constant rotation in muscle PDs as the shoulder joint rotated in the horizontal plane. In such fields, training in a small region resulted in generalization to near and far work spaces (80 cm). In one such field, the forces on the hand reversed directions for a given hand velocity with respect to the location of original training. Despite this, there was generalization. However, if the field was such that the change in the muscle PDs reversed as the work spaces changed, then performance was worse than performance of naive subjects. We suggest that the sensorimotor map of arm dynamics is represented in the brain by elements that globally encode the position of the arm but locally encode its velocity. The elements have preferred directions of movement but are modulated globally by the position of the shoulder joint. We suggest that tuning properties of cells in the motor system influence behavior and that this influence is reflected in the way that we learn dynamics of reaching movements.


Nature versus Nurture: Assessing the Impact of Strain Diversity and Pregrowth Conditions on Salmonella enterica, Escherichia coli, and Listeria Species Growth and Survival on Selected Produce Items.
Inoculation studies are important when assessing microbial survival and growth in food products. These studies typically involve the pregrowth of multiple strains of a target pathogen under a single condition; this emphasizes strain diversity. To gain a better understanding of the impacts of strain diversity ("nature") and pregrowth conditions ("nurture") on subsequent bacterial growth in foods, we assessed the growth and survival of Salmonella enterica (n = 5), Escherichia coli (n = 6), and Listeria (n = 5) inoculated onto tomatoes, precut lettuce, and cantaloupe rind, respectively. Pregrowth conditions included (i) 37°C to stationary phase (baseline), (ii) low pH, (iii) high salt, (iv) reduced water activity, (v) log phase, (vi) minimal medium, and (vii) 21°C. Inoculated tomatoes were incubated at 21°C; lettuce and cantaloupe were incubated at 7°C. Bacterial counts were assessed over three phases, including initial reduction (phase 1), change in bacterial numbers over the first 24 h of incubation (phase 2), and change over the 7-day incubation (phase 3). E. coli showed overall decline in counts (<1 log) over the 7-day period, except for a <1-log increase after pregrowth in high salt and to mid-log phase. In contrast, S. enterica and Listeria showed regrowth after an initial reduction. Pregrowth conditions had a substantial and significant effect on all three phases of S. enterica and E. coli population dynamics on inoculated produce, whereas strain did not show a significant effect. For Listeria, both pregrowth conditions and strain affected changes in phase 2 but not phases 1 and 3.IMPORTANCE Our findings suggest that inclusion of multiple pregrowth conditions in inoculation studies can best capture the range of growth and survival patterns expected for Salmonella enterica and Escherichia coli present on produce. This is particularly important for fresh and fresh-cut produce, where stress conditions encountered by pathogens prior to contamination can vary widely, making selection of a typical pregrowth condition virtually impossible. Pathogen growth and survival data generated using multiple pregrowth conditions will allow for more robust microbial risk assessments that account more accurately for uncertainty.


[PUBLIC AWARENESS ABOUT INTELLECTUAL DISABILITY, ITS CAUSES AND EFFECTIVENESS OF INTERVENTIONS BY SPECIALISTS].
The purpose of the study is to analyze perception of the adult population about intellectual disability (ID), its causes and effectiveness of specialist interventions. 1119 people were interviewed (men - 441, women - 678) aged 18 to 85 years (mean age - 34.3 ± 14.5 years). Urban residents - 851 people (76.1%), rural dwellers - 268 (23.9%). Each respondent was offered one vignette describing a sick child aged 8-10 with ID: typical, dyslalic, bradypsychic and dysphoric. Mathematical and statistical processing included descriptive statistics and calculation of the χ2 distribution. 49.1% of the respondents have correctly recognized ID in vignettes. Out of the incorrect answers, various psychological characteristics prevailed (25.3%) of the child; negative character traits with pessimistic assessments (23.2%); illness, including mental disorders (18.6%); defects in education and upbringing (15.6%). The respondents most often (38.5%) suggested assistance by psychologists, especially to patients with a bradypsychic variant of ID, a speech therapist - with a dyslalic one, teachers - with a typical one, psychiatrists - with a dysphoric one. 85.3% of the respondents expected improvement in the child's condition after the specialist intervention. The probable causes of ID included improper upbringing and disharmonious family relations, more often in case of a typical variant, hereditary burden and early childhood diseases - in dyslalic, alcohol consumption, poverty - in dysphoric, all of the above - in case of a bradypsychic variant. The study has identified an insufficient level of public awareness of ID, reflecting its delayed diagnosis in children, peculiarities of the "channels" for seeking assistance with excessively high expectations of the condition improvements.


Inference of nonlinear receptive field subunits with spike-triggered clustering.
Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. For parasol retinal ganglion cells in macaque retina, estimated subunits partitioned the receptive field into compact regions, likely representing aggregated bipolar cell inputs. Joint clustering revealed shared subunits between neighboring cells, producing a parsimonious population model. Closed-loop validation, using stimuli lying in the null space of the linear receptive field, revealed stronger nonlinearities in OFF cells than ON cells. Responses to natural images, jittered to emulate fixational eye movements, were accurately predicted by the subunit model. Finally, the generality of the approach was demonstrated in macaque V1 neurons.


In vivo and in vitro demonstration of herb-drug interference in human breast cancer cells treated with tamoxifen and trastuzumab.
In recent trends, patients with breast cancer seek integrative medical treatment when receiving either hormonal (tamoxifen [Tam]) or target (trastuzumab) therapy. Our previous in vitro studies demonstrated that the Chinese medicine Si-Wu-Tang (SWT) stimulates MCF-7 cell growth via activation of estrogen receptor α and human epidermal growth factor receptor 2 (HER2) signaling. The present study demonstrates herb-drug interference with cell proliferation in tumor-bearing mice treated with SWT and Tam in vivo and with proliferation capacity in breast cancer cells treated with SWT and trastuzumab in vitro. To assess in vivo SWT + Tam interference, we randomly separated female MCF-7-implanted athymic nude mice into five groups, namely, vehicle (n = 11), estradiol (n = 8), SWT (n = 8), Tam (n = 11), and SWT + Tam (n = 8). All mice were killed after 21 days of treatment. Body weight, uterine weight, tumor volume, and tumor weight were measured. To assess in vitro SWT-trastuzumab interference, we cotreated BT-474 and SK-BR-3 breast cancer cells with SWT and trastuzumab. This was followed by (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays and cell cycle analysis to measure cell proliferation and by Western blot analysis to analyze protein expression in growth-related signal pathways. SWT reversed Tam-induced antiproliferative effects on tumor weight and tumor volume and increased estrogen receptor α and N-cadherin expression in the SWT + Tam-treated group compared with the Tam-treated group. Furthermore, SWT reversed trastuzumab-induced antiproliferative activity in HER2 cell lines (SK-BR-3 and BT-474) through increased phosphorylation of the cell cycle regulatory protein p27(Kip1) and possibly of the antiapoptosis protein P38. Based on the in vivo and in vitro demonstration of herb-drug interference in breast cancer cells, we conclude that physicians should pay more attention to such interference when treating patients with receptor-positive (estrogen receptor-positive, progesterone receptor-positive, or HER2) breast cancers.


Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.
Studies on the in vitro susceptibility of SIV to integrase strand transfer inhibitors (INSTIs) have been rare. In order to determine the susceptibility of SIVmac239 to INSTIs and characterize the genetic pathways that might lead to drug resistance, we inserted various integrase (IN) mutations that had been selected with HIV under drug pressure with raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG) into the IN gene of SIV. We evaluated the effects of these mutations on SIV susceptibility to INSTIs and on viral infectivity. Sequence alignments of SIVmac239 IN with various HIV-1 isolates showed a high degree of homology and conservation of each of the catalytic triad and the key residues involved in drug resistance. Each of the G118R, Y143R, Q148R, R263K, and G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and replication fitness compared to wild-type virus. Using TZM-bl cells, we demonstrated that the Q148R and N155H mutational pathways conferred resistance to EVG (36- and 62-fold, respectively), whereas R263K also displayed moderate resistance to EVG (12-fold). In contrast, Y143R, Q148R, and N155H all yielded low levels of resistance to RAL. The combination of G140S/Q148R conferred high-level resistance to both RAL and EVG (>300- and 286-fold, respectively). DTG remained fully effective against all site-directed mutants except G118R and R263K. Thus, HIV INSTI mutations, when inserted into SIV, resulted in a similar phenotype. These findings suggest that SIV and HIV may share similar resistance pathways profiles and that SIVmac239 could be a useful nonhuman primate model for studies of HIV resistance to INSTIs. The goal of our project was to establish whether drug resistance against integrase inhibitors in SIV are likely to be the same as those responsible for drug resistance in HIV. Our data answer this question in the affirmative and show that SIV can probably serve as a good animal model for studies of INSTIs and as an early indicator for possible emergent mutations that may cause treatment failure. An SIV-primate model remains an invaluable tool for investigating questions related to the potential role of INSTIs in HIV therapy, transmission, and pathogenesis, and the present study will facilitate each of the above.