Biodegradation of furfuryl alcohol by indigenous Bacillus species of industrial effluent-contaminated sites: estimation, biokinetics and toxicity assessment of bio-transformed metabolites.
Furfuryl alcohol (FA) and other furanic compounds have garnered considerable attention in the quest for sustainable alternatives. FA-based resins have been used in various sectors that entail the release of FA into the environment. Hence, to ensure sustainability in this scenario, devising a dependable approach to its degradation is imperative. Given the crucial role of bacterial strains in the biodegradation of various organic pollutants, this study investigates the microbial degradation of FA, using bacterial strains isolated from sites that are constantly exposed to industrial waste. Three potential isolates were identified as B. paramycoides, B. cereus, and B. tequilensis by 16S rRNA gene sequencing. At a concentration of 300 µg/ml, these isolates demonstrated efficient FA degradation; 60-70% (at 300 µg/ml FA) and 50-60%, (at 500 µg/ml FA). Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC) analysis further supported the result that the bacterial isolates consumed FA as the carbon source. Liquid chromatography-mass spectrometry (LC-MS) facilitates the detection of the major metabolic intermediate product in which FA gets transformed. The prominent peaks at 113 and 119 m/z obtained in the MS spectra of the degraded FA samples indicated the possibility of the conversion of FA into furoic acid or levulinic acid. The phytotoxicity bioassay findings revealed the non-toxic nature of the bio-transformed products as compared to pure FA. This investigation presents the initial documentation of the FA degradative potential of Bacillus strains, thereby augmenting the understanding of the prospective implementation of Bacillus species in industrial waste treatment projects.


Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway.
The metastasis-suppressive activity of Nm23-H1 was previously correlated with its in vitro histidine protein kinase activity, but physiological substrates have not been identified. We hypothesized that proteins that interact with histidine kinases throughout evolution may represent partners for Nm23-H1 and focused on the interaction of Arabidopsis "two-component" histidine kinase ERS with CTR1. A mammalian homolog of CTR1 was previously reported to be c-Raf; we now report that CTR1 also exhibits homology to the kinase suppressor of Ras (KSR), a scaffold protein for the mitogen-activated protein kinase (MAPK) cascade. Nm23-H1 co-immunoprecipitated KSR from lysates of transiently transfected 293T cells and at endogenous protein expression levels in MDA-MB-435 breast carcinoma cells. Autophosphorylated recombinant Nm23-H1 phosphorylated KSR in vitro. Phosphoamino acid analysis identified serine as the major target, and two peaks of Nm23-H1 phosphorylation were identified upon high performance liquid chromatography analysis of KSR tryptic peptides. Using site-directed mutagenesis, we found that Nm23-H1 phosphorylated KSR serine 392, a 14-3-3-binding site, as well as serine 434 when serine 392 was mutated. Phosphorylated MAPK but not total MAPK levels were reduced in an nm23-H1 transfectant of MDA-MB-435 cells. The data identify a complex in vitro histidine-to-serine protein kinase pathway, which may contribute to signal transduction and metastasis.


Mycobacterium tuberculosis invades and replicates within type II alveolar cells.
Although Mycobacterium tuberculosis is assumed to infect primarily alveolar macrophages after being aspirated into the lung in aerosol form, it is plausible to hypothesize that M. tuberculosis can come in contact with alveolar epithelial cells upon arrival into the alveolar space. Therefore, as a first step toward investigation of the interaction between M. tuberculosis and alveolar epithelial cells, we examined the ability of M. tuberculosis to bind to and invade alveolar epithelial cells in vitro. The H37Rv and H37Ra strains of M. tuberculosis were cultured to mid-log phase and used in both adherence and invasion assays. The A549 human type II alveolar cell line was cultured to confluence in RPMI 1640 supplemented with 5% fetal bovine serum, L-glutamine, and nonessential amino acids. H37Rv was more efficient in entering A549 cells than H37Ra, Mycobacterium avium, and Escherichia coli Hb101, and nonpiliated strain (4.7% +/- 1.0% of the initial inoculum in 2 h compared with 3.1% +/- 0.8%, 2.1% +/- 0.9%, and 0.03% +/- 0.0%, respectively). The invasion was more efficient at 37 degrees C than 30 degrees C (4.7% +/- 1.0% compared with 2.3% +/- 0.8%). H37Rv and H37Ra were both capable of multiplying intracellularly at a similar ration over 4 days. Binding was inhibited up to 55.7% by anti-CD51 antibody (antivitronectin receptor), up to 55% with anti-CD29 antibody (beta(1) integrin), and 79% with both antibodies used together. Update of M. tuberculosis H37Rv was microtubule and microfilament dependent. It was inhibited by 6l.4% in the presence of 10 micron colchicine and by 72.3% in the presence of 3 micron cytochalasin D, suggesting two separate pathways for uptake. Our results show that M. tuberculosis is capable of invading type II alveolar epithelial cells and raise the possibility that invasion of alveolar epithelial cells is associated with the pathogenesis of lung infection.


Evidence of intrafamilial transmission of rotavirus in a birth cohort in South India.
Transmission of rotavirus infection was studied in a birth cohort of children based in an urban slum in Vellore and their familial contacts. Contemporaneous samples from index patients and their familial contacts were collected for analysis in three different settings. Firstly, samples were collected from familial contacts during a period of rotavirus infection in children from the cohort. Secondly, on occasions when a family member had rotavirus diarrhea, samples from the cohort child were taken for analysis. Lastly, asymptomatic surveillance samples collected at predetermined time points from both the cohort child and familial contacts were analyzed. From 560 samples collected from family members during symptomatic and asymptomatic rotavirus infections in these children, three rotavirus transmissions were identified, accounting for a secondary attack rate of 0.54%. In four instances of rotavirus diarrhea in a family member, one infection was transmitted to the cohort child. Nucleotide sequence and phylogenetic analysis demonstrated a high degree of similarity in all these pairs ranging between 99% and 100% at both the nucleotide and the deduced amino acid levels, highly suggestive of person-to-person transmission of rotavirus infection. There was complete concordance of rotavirus genotyping between these pairs. No transmission events were noted from 14 asymptomatic rotavirus infections identified during routine surveillance of family members. This study is the first to use phylogenetic analysis to study the intrafamilial spread of rotavirus infection.


Long-term pressure monitoring with arterial applanation tonometry: a non-invasive alternative during clinical intervention?
Arterial tonometry is a non-invasive technique for continuous registration of arterial pressure waveforms. This study aims to assess tonometric blood pressure recording (TBP) as an alternative for invasive long-term bedside monitoring. A prospective study was set up where patients undergoing neurosurgical intervention were subjected to both invasive (IBP) and non-invasive (TBP) blood pressure monitoring during the entire procedure. A single-element tonometric pressure transducer was used to better investigate different inherent error sources of TBP measurement. A total of 5.7 hours of combined IBP and TBP were recorded from three patients. Although TBP performed fairly well as an alternative for IBP in steady state scenarios and some short-term variations, it could not detect relevant long-term pressure variations at all times. These findings are discussed in comparison to existing work. Physiological alterations at the site of TBP measurement are highlighted as a potentially important source of artifacts. It is concluded that at this point arterial tonometry remains not enough understood for long-term use during a delicate operative procedure. Physiological changes at the TBP measurement site deserve further investigation before tonometry technology is to be considered as an non-invasive alternative for long-term clinical monitoring.


The asymptomatic newborn and risk of cerebral palsy.
We investigated whether infants weighing over 2500 g who had experienced one or more of 14 late pregnancy or birth complications, but who were free of certain signs in the nursery period were at increased risk of cerebral palsy (CP). The signs evaluated were decreased activity after the first day of life, need for incubator care for three or more days, feeding problems, poor suck, respiratory difficulty, or neonatal seizures. More than 90% of the infants weighing over 2500 g had none of these signs. In asymptomatic infants with one or more birth complications, the rate of CP by 7 years of age was 2.3/1000; among asymptomatic infants whose births were uncomplicated, the rate of CP was 2.4/1000. The risk for CP rose with number of abnormal neonatal signs, and children with sustained neonatal abnormalities were at higher risk than those whose abnormalities were transient. Most children with CP did not derive from groups at increased risk. The full-term infant whose birth was complicated but who was free of certain abnormal signs in the newborn period was not at increased risk of CP.


Inhibiting intestinal NPC1L1 activity prevents diet-induced increase in biliary cholesterol in Golden Syrian hamsters.
Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the enterocyte and is the target of the novel cholesterol absorption inhibitor, ezetimibe. These studies used the Golden Syrian hamster as a model to delineate the changes in the relative mRNA expression of NPC1L1 and other proteins that regulate sterol homeostasis in the enterocyte during and following cessation of ezetimibe treatment and also to address the clinically important question of whether the marked inhibition of cholesterol absorption alters biliary lipid composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of the gastrointestinal tract, liver, and gallbladder. In the first study, female hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg.day(-1).kg body wt(-1). At this dose, cholesterol absorption fell by 82%, fecal neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal cholesterol synthesis increased more than twofold, but there were no significant changes in either fecal bile acid excretion or biliary lipid composition. The ezetimibe-induced changes in intestinal cholesterol handling were reversed when treatment was withdrawn. In a second study, male hamsters were given a diet enriched in cholesterol and safflower oil without or with ezetimibe. The lipid-rich diet raised the absolute and relative cholesterol levels in bile more than fourfold. This increase was largely prevented by ezetimibe. These data are consistent with the recent finding that ezetimibe treatment significantly reduced biliary cholesterol saturation in patients with gallstones.


Reef size and isolation determine the temporal stability of coral reef fish populations.
Temporal variance in species abundance, a potential driver of extinction, is linked to mean abundance through Taylor's power law, the empirical observation of a linear log-log relationship with a slope between 1 and 2 for most species. Here we test the idea that the slope of Taylor's power law can vary both among species and spatially as a function of habitat area and isolation. We used the world's most extensive database of coral reef fish communities comprising a 15-year series of fish abundances on 43 reefs of Australia's Great Barrier Reef. Greater temporal variances were observed at small and isolated reefs, and lower variances at large and connected ones. The combination of reef area and isolation was associated with an even greater effect on temporal variances, indicating strong empirical support for the idea that populations on small and isolated reefs will succumb more frequently to local extinction via higher temporal variability, resulting in lower resilience at the community level. Based on these relationships, we constructed a regional predictive map of the dynamic fragility of coral reef fish assemblages on the Great Barrier Reef.


Is empowerment in sexual health measurable? A scoping review of definitions and measurement indicators.
The concept of empowerment in sexual health is widely used in health promotion. This scoping review aims to identify how it is defined and measured. PubMed, Sage Journals, PsycInfo and the Web of Science are data sources. The inclusion criteria for studies were as follows: (1) an analysis of empowerment in sexual health, (2) quantitative evaluation and (3) publication in a peer-reviewed journal in French or English since January 1996. Data were extracted using a summary table of the definitions and indicators of empowerment in sexual health. Of the 2181 articles found, 29 met the inclusion criteria. Only 4 studies on 29 clearly defined empowerment in sexual health. Five dimensions emerged from the indicators used in the 29 studies in relation to sexual empowerment (social participation, participation in decision making, power to act, sexual health knowledge and gender norms), with two types of indicators: indicators unspecific to sexual health, which can be viewed as empowerment basic skills, and indicators specific to sexual health. Most studies concerned women and focused on individual empowerment, with a lack of measure of collective and structural levels of empowerment. Despite great heterogeneity in the definitions and indicators used, a set of core indicators emerged: participation in decision making, sexual negotiation power and sexual communication skills, knowledge and use of contraceptive methods, and HIV and sexually transmitted infections risk perception. This set could be systematically used in each study based on sexual empowerment concept, completed by supplementary indicators considering the specific context.


Molecular cloning of the gene for p85 that regulates the initiation of cytokinesis in Tetrahymena.
Tetrahymena p85 is localized to the presumptive division plane before division furrow formation; its molecular weight in SDS-polyacrylamide gel electrophoresis differs in wild-type and temperature-sensitive cell-division-arrest mutant cdaA1 cells. At the restrictive temperature, p85 localization and division furrow formation are not observed in cdaA1 cells. In this study, we purified p85 and cloned a wild-type p85 cDNA. The deduced amino acid sequence of p85 was composed mainly of two kinds of repeat sequences. One of these contained regions homologous to a calmodulin-binding site and a part of actin, and the other contained a region homologous to a part of a cdc2 kinase homologue. Moreover, we cloned a cDNA encoding the cdaA1 p85. There was no difference in the predicted amino acid sequences of wild-type and cdaA1 p85, suggesting that the difference in molecular weight between p85 in wild-type and mutant cells is caused by a disorder of posttranslational-modification mechanisms of p85 in the cdaA1 cell.


Purification and partial molecular characterization of GRP94, an ER resident chaperone.
GRP94 is a resident glycoprotein of the endoplasmic reticulum (ER) and a member of the hsp90 family of molecular chaperones. Current experimental evidence indicates that GRP94 functions in an as yet undefined manner in protein folding and assembly in the ER. We report a rapid, high-yield GRP94 purification procedure that yields milligram quantities of homogeneous protein suitable for structural and biochemical analyses. Beginning with a rough microsome fraction derived from porcine pancreas, GRP94 was isolated by partial detergent extraction, anion exchange, and gel filtration chromatography. With this procedure, approximately 3 mg of homogeneous GRP94 can be prepared from a 25-g pancreas. Heterogeneity in the migration of purified GRP94 on native and denaturing PAGE was observed and demonstrated to reflect variability in the N-linked glycosylation state of the protein. Analysis by native and two-dimensional nonreducing/reducing gels indicated that the protein exists as a dimer of noncovalently associated subunits. The membrane localization of GRP94 in isolated pancreatic microsomes was assessed by alkali and detergent extraction. By comparison with the resident ER integral membrane protein TRAPalpha, GRP94 exists as a soluble, lumenal protein.


Adaptive memory: Survival processing increases both true and false memory in adults and children.
Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a survival, moving, or pleasantness scenario. Even though the survival advantage was demonstrated for true recall, there also was an unexpected increase in false memories in the survival condition. Similarly, younger and older children in Experiment 2 displayed superior true recall but also higher rates of false memories in a survival condition. Experiment 3 showed that in adults false memories were also more likely to occur in the survival condition when categorized lists instead of Deese-Roediger-McDermott (DRM)-like word lists were used. In all three experiments, no survival recall advantage was found when net accuracy scores that take the total output into account were used. These findings question whether survival processing is an adaptive memory strategy per se, as such processing not only enriches true recall but simultaneously amplifies the vulnerability to false memories.


The multifarious roles of Tol-Pal in Gram-negative bacteria.
In the 1960s several groups reported the isolation and preliminary genetic mapping of Escherichia coli strains tolerant towards the action of colicins. These pioneering studies kick-started two new fields in bacteriology; one centred on how bacteriocins like colicins exploit the Tol (or more commonly Tol-Pal) system to kill bacteria, the other on the physiological role of this cell envelope-spanning assembly. The following half century has seen significant advances in the first of these fields whereas the second has remained elusive, until recently. Here, we review work that begins to shed light on Tol-Pal function in Gram-negative bacteria. What emerges from these studies is that Tol-Pal is an energised system with fundamental, interlinked roles in cell division - coordinating the re-structuring of peptidoglycan at division sites and stabilising the connection between the outer membrane and underlying cell wall. This latter role is achieved by Tol-Pal exploiting the proton motive force to catalyse the accumulation of the outer membrane peptidoglycan associated lipoprotein Pal at division sites while simultaneously mobilising Pal molecules from around the cell. These studies begin to explain the diverse phenotypic outcomes of tol-pal mutations, point to other cell envelope roles Tol-Pal may have and raise many new questions.


Burden of Care for Children with Bronchiectasis from Parents/Carers Perspective.
Bronchiectasis is a neglected chronic respiratory condition. In children optimal appropriate management can halt the disease process, and in some cases reverse the radiological abnormality. This requires many facets, including parental/carer bronchiectasis-specific knowledge, for which there is currently no such published data. Further, the importance of patient voices in guiding clinical research is becoming increasingly appreciated. To address these issues, we aimed to describe the voices of parents of children with bronchiectasis relating to (a) burden of illness and quality of life (QoL), (b) their major worries/concerns and (c) understanding/management of exacerbations. The parents of 152 children with bronchiectasis (median age = 5.8 years, range 3.5-8.4) recruited from the Queensland Children's Hospital (Australia) completed questionnaires, including a parent-proxy cough-specific QoL. We found that parents of children with bronchiectasis had impaired QoL (median 4.38, range 3.13-5.63) and a high disease burden with median 7.0 (range 4.0-10.0) doctor visits in 12-months. Parental knowledge varied with only 41% understanding appropriate management of an exacerbation. The highest worry/concern expressed were long-term effects (n = 42, 29.8%) and perceived declining health (n = 36, 25.5%). Our study has highlighted the need for improved education, high parental burden and areas of concern/worry which may inform development of a bronchiectasis-specific paediatric QoL tool.


[Correlation between E.N.G. changes and the evolution of the hematic constants in patients under prolonged hemodialysis and renal transplantation].
An evolutive study of the E.N.G. on 25 patients affected of chronic renal failure (c.r.f.) in their previous periods and during the dialysis programme was developed. At the same time a large study on various serum changes was carried on. It is observed that the motor conduction velocity (M.C.V.) shows a decreasing evolution during dialysis, which mathematical patters is a branch of an equilateral hyperbola, of equation: (see article) The Na and K evolutive curves are also significatively fitted to the same mathematical pattern. It is observed a direct and inverse lineal correlation between M.C.V. values and those ones of the Na and K respectively, with p less than 0,05 and p less than 0,01. It is not observed any correlation of significatively value with the other serum parameters studied (R.A., Cl, Urea, Total proteins, Hematocrit, Ca, P, Creatinine, fluids and acid-base equilibrium). After a renal transplantation the M.C.V. presents a growing trayectory of the same mathematical pattern described before, reaching normal values about a year post-transplantion. The levels of Sodium serum follow a parallel trayectory than that one of the M.C.V. The recovery of the remainders serum parameters after renal transplantion occour during the first week, except for the hematocrit. It only remains a parallelism between the evolutive changes of M.C.V./Natremia during dialysis stage and after renal transplantion. These results seem to show a close dependence between variation of M.C.V. and Natremia. The hipoxia role over the sodium pump and the consequent variations of Natremia are discussed.


Burning water: a comparative analysis of the energy return on water invested.
While various energy-producing technologies have been analyzed to assess the amount of energy returned per unit of energy invested, this type of comprehensive and comparative approach has rarely been applied to other potentially limiting inputs such as water, land, and time. We assess the connection between water and energy production and conduct a comparative analysis for estimating the energy return on water invested (EROWI) for several renewable and non-renewable energy technologies using various Life Cycle Analyses. Our results suggest that the most water-efficient, fossil-based technologies have an EROWI one to two orders of magnitude greater than the most water-efficient biomass technologies, implying that the development of biomass energy technologies in scale sufficient to be a significant source of energy may produce or exacerbate water shortages around the globe and be limited by the availability of fresh water.


Divergent Regulation of ER and Kiss Genes by 17β-Estradiol in Hypothalamic ARC Versus AVPV Models.
Kisspeptin (Kiss) and G-protein-coupled receptor (Gpr)54 have emerged as key regulators of reproduction. 17β-estradiol (E2)-mediated regulation of these neurons is nuclei specific, where anteroventral periventricular (AVPV) Kiss neurons are positively regulated by E2, whereas arcuate nucleus (ARC) neurons are inhibited. We have generated immortalized Kiss cell lines from male and female adult-derived murine hypothalamic primary culture, as well as cell lines from microdissected AVPV and ARC from female Kiss-green fluorescent protein (GFP) mice. All exhibit endogenous Kiss-1 expression, estrogen receptors (ER)s (ERα, ERβ, and Gpr30), as well as known markers of AVPV Kiss neurons in the mHypoA-50 and mHypoA-Kiss/GFP-4, vs markers of ARC Kiss neurons in the mHypoA-55 and the mHypoA-Kiss/GFP-3 lines. There was an increase in Kiss-1 mRNA expression at 24 hours in the AVPV lines and a repression of Kiss-1 mRNA at 4 hours in the ARC lines. An E2-mediated decrease in ERα mRNA expression at 24 hours in the AVPV cell lines was detected, and a significant decrease in Gpr30, ERα, and ERβ mRNA levels at 4 hours in the ARC cell lines was evident. ER agonists and antagonists determined the specific ERs responsible for mediating changes in gene expression. In the AVPV, ERα is required but not ERβ or GPR30, vs the ARC Kiss-expressing cell lines that require GPR30, and either ERα and/or ERβ. We determined cAMP response element-binding protein 1 was necessary for the down-regulation of Kiss-1 mRNA expression using small interfering RNA knockdown in the ARC cell model. These studies elucidate some of the molecular events involved in the differential E2-mediated regulation of unique and specific Kiss neuronal models.


A role for Gic1 and Gic2 in Cdc42 polarization at elevated temperature.
The conserved Rho-family GTPase Cdc42 is a master regulator of polarity establishment in many cell types. Cdc42 becomes activated and concentrated in a region of the cell cortex, and recruits a variety of effector proteins to that site. In turn, many effectors participate in regulation of cytoskeletal elements in order to remodel the cytoskeleton in a polarized manner. The budding yeast Saccharomyces cerevisiae has served as a tractable model system for studies of cell polarity. In yeast cells, Cdc42 polarization involves a positive feedback loop in which effectors called p21-activated kinases (PAKs) act to recruit a Cdc42-directed guanine nucleotide exchange factor (GEF), generating more GTP-Cdc42 in areas that already have GTP-Cdc42. The GTPase-interacting components (GICs) Gic1 and Gic2 are also Cdc42 effectors, and have been implicated in regulation of the actin and septin cytoskeleton. However, we report that cells lacking GICs are primarily defective in polarizing Cdc42 itself, suggesting that they act upstream as well as downstream of Cdc42 in yeast. Our findings suggest that feedback pathways involving GTPase effectors may be more prevalent than had been appreciated.


Mechanisms of alcohol intoxication in a rodent model: blunted alcohol-opposing reaction in "alcohol-sensitive" rats.
In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena.


Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells: A Translational Biologic Alternative for Healing Critical Bone Defects.
Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis. Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two- and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model. Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell- and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two- and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation. Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.


A lab-on-chip device for the sample-in-result-out detection of viable Salmonella using loop-mediated isothermal amplification and real-time turbidity monitoring.
Rapid screening of foodborne pathogens is key to prevent food poisoning. In this study, a lab-on-chip device was developed for rapid, automatic and sensitive detection of viable Salmonella typhimurium using loop-mediated isothermal amplification (LAMP) and smartphone real-time turbidity monitoring. First, magnetic nanoparticles (MNPs) coated with anti-Salmonella capture antibodies in propidium monoazide (PMA) were fully mixed with bacterial samples using two active magnetic stirring mixers at reverse rotating directions, and incubated in the serpentine channel with 470 nm blue light exposure, allowing specific formation of magnetic bacteria and sufficient PMA pretreatment of the DNA of dead bacteria. Then, the PMA-treated magnetic bacteria were separated in the separation chamber using the magnetic field and their genomic DNA templates were extracted using lysis buffer at 70 °C. Finally, the viable bacteria's DNA was amplified using LAMP in the detection chamber preloaded with the lyophilized LAMP reagents at 67.5 °C after blocking with paraffin oil to avoid aerosol cross contamination. Finally, the turbidity of the LAMP reaction system was monitored in a real-time manner for the quantitative detection of viable bacteria. The experimental results demonstrated that this device was able to automatically detect viable Salmonella as low as 14 CFU mL-1 in spiked chicken meat supernatants within 1.5 h. This device is very promising to provide a sample-in-result-out solution for the in-field detection of Salmonella and could be easily extended for other foodborne pathogens.


Acute static vibration-induced stretching enhanced muscle viscoelasticity but did not affect maximal voluntary contractions in footballers.
The aim of this study was to compare the effects of acute vibration-enhanced static stretching and/or static stretching alone on the strength and flexibility of the hamstrings and quadriceps muscles. Twenty-one male footballers participated in this study (21.9 ± 1.8 years; 75.54 ± 7.3 kg; 178.7 ± 6.5 cm). The experiment started with 5 minutes standardized warm-up followed by (a) baseline flexibility pretest (Split Test); (b) maximal voluntary flexion and extension (isokinetic strength) of the knee; (c) Treatment or Sham involving 45-second stretch with or without vibration for the hamstring and quadriceps muscle groups with 10-second rest between; and (d) posttest repeating the measures of the pretest. Each player randomly performed both trials on separate occasions. The vibration device operated at 35 Hz with 2 mm amplitude. Stretching with vibration statistically increased hamstring flexibility by 7.8% (p ≤ 0.05) when compared with stretching without vibration. No statistical differences for hamstring or quadriceps strength were noted between treatment conditions. There was no statistical correlation between flexibility and strength measurements. In conclusion, flexibility increased with vibration-enhanced static stretching; however, no change was evident in the maximal voluntary contractions of the knee flexors and extensors.


Bilateral optic disk edema and blindness as initial presentation of acute lymphocytic leukemia.
To report bilateral optic disk edema and blindness as the unusual initial presentation of acute lymphocytic leukemia (ALL) in an adult. A 19-year-old man presented with a history of headaches, back pain, and 10 days of worsening vision that progressed to blindness. Ocular examination revealed light perception acuity in the right eye and no light perception in the left eye. Fundus examination revealed bilateral profound optic disk edema, tortuous vessels, and retinal hemorrhages. Acute lymphocytic leukemia was diagnosed with complete blood count and bone marrow biopsy. Head computed tomography and magnetic resonance imaging, were normal. Lumbar puncture revealed normal opening pressure. Ocular ultrasonography showed bilateral optic nerve enlargement. Interventional case report and literature review. The presumptive diagnosis of leukemic infiltration of the optic nerves was made, and urgent radiotherapy, intrathecal methotrexate, and intravenous daunorubicin were instituted. Visual acuity improved to hand motions in the right eye. Acute lymphocytic leukemia can rarely present in adults as visual changes due to leukemic optic nerve infiltration. Radiation treatment should be considered as an urgent treatment modality for this rare condition.


A mutation which affects both the specificity of PtsG sugar transport and the regulation of ptsG expression by Mlc in Escherichia coli.
Normally glucosamine (GlcN) is not a substrate for EIICB(Glc) of the glucose phosphotransferase system (PTS), encoded by ptsG, but it is transported by the mannose (Man) PTS, encoded by manXYZ. A mutation, umgC, has been described in Escherichia coli which allows a strain mutated in the Man PTS to grow on GlcN. The umgC mutation was mapped to the ptsG region and was proposed to make ptsG expression constitutive. Transcription of ptsG is regulated by the repressor Mlc so that mutations in mlc enhance the expression of ptsG. An mlc mutation, however, is not sufficient to allow good growth on GlcN, unlike the umgC mutation. The umgC mutation is shown to enhance expression of ptsG even in the absence of any PTS sugar transport, but the increase is greater in the presence of GlcN or Man. The umgC mutation also increases expression of the ptsHI and manXYZ operons, which are both regulated by Mlc. The umgC mutation was sequenced and two mutations were found: one, G176D, within the IIC membrane domain and the second, E472K, within the soluble IIB domain of PtsG. The cloned UmgC allele shows the enhanced transport and regulatory characteristics of the chromosomal mutation. Analysis of the two mutations present individually on plasmids shows that the IIC mutation is responsible for both the effect on sugar specificity and regulation.


Nature based solutions to mitigate soil sealing in urban areas: Results from a 4-year study comparing permeable, porous, and impermeable pavements.
Soil sealing is one of the most pervasive forms of soil degradation that follows urbanization and, despite innovative pavements (i.e. pervious) are being installed in urban areas to mitigate it, there is little research on the effects of pervious pavements on soil water and carbon cycle and on the physiology of urban trees. The aim of this 4-year experiment was to assess the effects of three pavements, differing in permeability to water and gases, on some soil physical parameters, and on growth and physiology of newly planted Celtis australis and Fraxinus ornus. Treatments were: 1) impermeable pavement (asphalt on concrete sub-base); 2) permeable pavement (pavers on crushed rock sub-base); 3) porous design (porous pavement on crushed rock sub-base); 4) control (unpaved soil, kept free of weed by chemical control). Soil (temperature, moisture, oxygen content and CO2 efflux) and plant (above- and below-ground growth, leaf gas exchange, chlorophyll fluorescence, water relations) parameters were measured. All types of pavements altered the water cycle compared to unpaved soil plots, but this disturbance was less intense in porous pavements than in other soil cover types. Porous pavements allowed both higher infiltration and evaporation of water than both pavers and asphalt. Reduction of evaporative cooling from soil paved with permeable and impermeable pavements contributed to significant soil warming: at 20cm depth, soils under concrete pavers and asphalt were 4 and 5°C warmer than soil covered by porous pavements and unpaved soils, respectively. Thus, enhancing evaporation from paved soil by the use of porous pavements may contribute to mitigating urban heat islands. CO2 greatly accumulated under impermeable and permeable pavements, but not under porous pavements, which showed CO2 efflux rates similar to control. Soil oxygen slightly decreased only beneath asphalt. Growth of newly planted C. australis and F. ornus was little affected by pavement type. Tree transpiration rapidly depleted soil moisture compared to the not-planted scenario, but soil moisture did not fall below wilting point (particularly in the deeper soil layers, i.e. 40-50cm) in any treatment. While C. australis showed similar leaf gas exchange and water relations in all treatments, F. ornus showed a depression in CO2 assimilation and slight signs of stress of the photosynthetic apparatus when planted in soil covered with impermeable pavement. The effects of soil cover with different materials on tree growth and physiology were little, because newly planted trees have most of their roots still confined in the unpaved planting pit. Still, the reduction of soil sealing around the planting pit triggered the establishment of sensitive species such as ash. Further research is needed to assess the effects of different pavement types on established, larger trees.


Predicting adverse drug reactions using publicly available PubChem BioAssay data.
Adverse drug reactions (ADRs) can have severe consequences, and therefore the ability to predict ADRs prior to market introduction of a drug is desirable. Computational approaches applied to preclinical data could be one way to inform drug labeling and marketing with respect to potential ADRs. Based on the premise that some of the molecular actors of ADRs involve interactions that are detectable in large, and increasingly public, compound screening campaigns, we generated logistic regression models that correlate postmarketing ADRs with screening data from the PubChem BioAssay database. These models analyze ADRs at the level of organ systems, using the system organ classes (SOCs). Of the 19 SOCs under consideration, nine were found to be significantly correlated with preclinical screening data. With regard to six of the eight established drugs for which we could retropredict SOC-specific ADRs, prior knowledge was found that supports these predictions. We conclude this paper by predicting that SOC-specific ADRs will be associated with three unapproved or recently introduced drugs.


Radical hysterectomy case volume and cervical cancer treatment in the era of COVID-19: A multi-site analysis of National Cancer Institute-designated Comprehensive Cancer Centers.
To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.


Active Choice and Financial Incentives to Increase Rates of Screening Colonoscopy-A Randomized Controlled Trial.
Behavioral economic approaches could increase uptake for colorectal cancer screening. We performed a randomized controlled trial of 2245 employees to determine whether an email containing a phone number for scheduling (control), an email with the active choice to opt in or opt out (active choice), or the active choice email plus a $100 incentive (financial incentive) increased colonoscopy completion within 3 months. Higher proportions of participants in the financial incentive group underwent screening (3.7%) than in the control (1.6%) or active choice groups (1.5%) (P = .01 and P < .01). We found no difference in uptake of screening between the active choice and control groups (P = .88). The $100 conditional incentive modestly but significantly increased colonoscopy use. ClinicalTrials.gov no: NCT02660671.


XY sex reversal in the wood lemming is associated with deletion of Xp21-23 as revealed by chromosome microdissection and fluorescence in situ hybridization.
In the wood lemming (Myopus schisticolor), XY sex reversal occurs naturally because of the presence of an X chromosome variant designated X*. The two types of X chromosome, X and X*, can be distinguished by G-banding, and analyses have demonstrated complex rearrangements of the short arm of X*. Here, chromosomal microdissection, degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and fluorescence in situ hybridization (FISH) techniques have been used to generate and map DNA probes for different parts of the X and X* chromosomes. The results showed that the region of Xp21-23 is deleted from the X* and some of the deleted DNA sequences are homologous to the mouse gamma-satellite. The deletion must be associated with the sex reversal in this species. FISH experiments with dissected probes of X and distal half of Xq provided evidence for presence of homologous sequences between large regions of the X and Y chromosomes, including euchromatic and heterochromatic parts of the sex chromosomes. The findings of this study will be of significance for further cloning of important candidate gene(s) responsible for the XY sex reversal.


The structure and properties of graphene on gold nanoparticles.
Graphene covered metal nanoparticles constitute a novel type of hybrid material, which provides a unique platform to study plasmonic effects, surface-enhanced Raman scattering (SERS), and metal-graphene interactions at the nanoscale. Such a hybrid material is fabricated by transferring graphene grown by chemical vapor deposition onto closely spaced gold nanoparticles produced on a silica wafer. The morphology and physical properties of nanoparticle-supported graphene are investigated by atomic force microscopy, optical reflectance spectroscopy, scanning tunneling microscopy and spectroscopy (STM/STS), and confocal Raman spectroscopy. This study shows that the graphene Raman peaks are enhanced by a factor which depends on the excitation wavelength, in accordance with the surface plasmon resonance of the gold nanoparticles, and also on the graphene-nanoparticle distance which is tuned by annealing at moderate temperatures. The observed SERS activity is correlated with the nanoscale corrugation of graphene. STM and STS measurements show that the local density of electronic states in graphene is modulated by the underlying gold nanoparticles.


[Incretin hormones in the treatment of type 2 diabetes. Part II. Incretins - new possibilities for pharmacotherapy of type 2 diabetes].
In the pathogenesis of diabetes type 2, increasing insulin resistance is accompanied by dysfunction of pancreatic islet b cells. It is hypothesized that at the basis of this pathology lies an incretin defect of insulinotropic gut-derived hormones, relying on decreased secretion of GLP-1 (glucagon-like peptide 1), with preserved insulinotropic effect, whereas GIP (glucose-dependent insulinotropic polypeptide) secretion remains within physiological limits, but its action is mostly impaired due to total loss of possibility for stimulation of the second phase insulin secretion. Possibilities for pharmacological correction of incretin defect create an opportunity of causative treatment of diabetes and provide basis for development of research on a new group of drugs which promote hypoglycemia. In the presence of these findings there are many ongoing clinical studies with the use of GLP-1 analogues or GLP-1 receptors activators (GLP-1 agonists), as well as the inhibitors of dipeptidyl peptidase IV (DPP-IV), the enzyme responsible for incretin proteolysis, in the treatment of type 2 diabetes. Multidirectional, glucoregulative mechanism of action of these drugs, aiming at the pathogenesis of the disease, restores the proper function of the intestinal-pancreatic axis in subjects with type 2 diabetes and ensures good metabolic control and improvement in quality of life in this group of patients.


Addressing spirituality in pediatric hospice and palliative care.
Hospice and palliative care principles mandate clinicIans to provide "total" care to patients and their families. Such care incorporates not only physical, emotional, and psychosocial care, but spiritual care as well. Even though considerable attention has been directed to spiritual issues for adult patients in hospice and palliative care, spirituality in pediatric palliative care has been virtually neglected. The need for guidelines to assess spirituality in this population was identified as a priority issue by members of a subcommittee of the Children's International Project on Children's Palliative/Hospice Services, created under the auspices of the National Hospice Organization. Committee members, based on their clinical, research, and personal experiences, identified several aspects relevant to spirituality in general, and to spirituality in pediatric palliative care in particular, and developed guidelines for clinicians in pediatric palliative care. The purpose of this paper is to share the results of this committee's work and, in particular, to present their guidelines for addressing spiritual issues in children and families in pediatric hospice and palliative care.


Digestive development in neonatal dairy calves with either whole or ground oats in the calf starter.
A series of 3 trials was conducted to determine effects of whole or ground oats in starter grain on reticulorumen fermentation and digestive system development of preweaned calves. Male Holstein calves (43.1±2.3kg at birth; n=8, 9, and 7 for trials 1, 2, and 3, respectively) were housed in individual pens in a heated facility; bedding was covered with landscape fabric to prevent consumption of bedding by the calves. In trials 1 and 2 only, calves were fitted with rumen cannulas by wk 2 of life. In all trials, a fixed amount of starter (containing 25% oats either ground and in the pellet or whole) was offered daily; orts were fed through the cannula in trials 1 and 2. Calves were randomly assigned to an all-pelleted starter or pellets plus whole oats. Rumen contents (trials 1 and 2) were sampled weekly at -8, -4, 0, 2, 4, 8, and 12 h after grain feeding for determination of pH and volatile fatty acids. Calves were killed 3 wk (trial 1) or 4 wk (trials 2 and 3) after grain was offered; organs were harvested, emptied, rinsed, and weighed to gauge digestive organ development. Starter intake was not different between treatments. Weekly measurements of rumen digesta pH did not change and only subtle changes were observed in molar proportions of individual volatile fatty acids. Molar proportion of butyrate and pH linearly decreased with age, whereas acetate proportion increased. Reticulorumen weight and papillae length tended to be greater for calves fed pelleted starter, whereas abomasum weight was greater for calves fed pellets plus whole oats. Fecal particle size and starch content were greater for calves fed pellets plus whole oats. Under the conditions of this study, physical form of oats in starter grain did not affect rumen fermentation measurements; greater rumen weight and papillae length in calves fed pelleted starter may be the result of greater nutrient availability of ground oats. Under the conditions of this study with young calves on treatments for <4 wk, increasing particle size of the starter by feeding whole oats did not affect rumen fermentation nor did it improve digestive system development.


[Pulmonary embolic ischemia: clinical and experimental aspects].
Pulmonary ischemia is usually related with embolics mechanisms, and this mechanic artery occlusion is not always followed by severe ischemic consequences, because the bronchial circulation changes supply the areas without blood flow. However, small artery vascular remodeling occurs, related to persistent high pulmonary pressure levels, mainly in the chronic pulmonary thromboembolism. Experimental models have been produced to study the relation-ship between mechanic artery occlusion, pulmonary hypertension and vascular remodeling, however, more systematic evaluation is necessary to understand such a these relation-ship, in the ischemic and not ischemic lung parenchyma.


Glucocorticoid receptors in lymphoid tumors.
There is a range of levels of glucocorticoid receptor numbers seen in the various subclasses of acute lymphatic leukemia (ALL). This variability cannot be explained by the known correlation between active cell proliferation and an increase in the number of receptors, since the tumors with the highest growth fraction (i.e., Burkitt's lymphoma and T-cell leukemia) tend to have lower average receptor numbers than do tumors with lower growth fractions such as common ALL. All clinical specimens from patients with lymphatic leukemia have some measurable level of glucocorticoid receptors; therefore, the resistance seen in vivo cannot be explained by the lack of receptors. However, there has been a positive correlation, in our hands, with receptor level and prognosis. On the basis of in vitro models, it is proposed that perhaps the high receptor cell lines (i.e., common ALL of childhood) have relative stability of their genetic material making glucocorticoid-resistant mutations less likely to occur in patients with these cells than in low-receptor cell lines (i.e., T-cell leukemia). This greater genetic variability in the low-receptor lines could account for the earlier emergence of clinical glucocorticoid resistance in these patients.


[Volatile compounds in air and oral saliva in healthy people, and in periodontitis and gingivitis patients].
21 healthy persons, 7 patients with chronic generalized periodontitis and 4 patients with chronic generalized gingivitis aged between 18 and 42 years were examined. Air from the oral cavity was collected with a special device; liquid samples were collected by washing the oral cavity with sterile water. Chemical compounds of the air and the washed liquid were analyzed by chromato-mass-spectrometry, gas-adsorption and gas-liquid chromatography. The content of dimethyl sulphide, dimethyl disulphide increased in the oral air and such volatile short chain fatty acids (VSCFA) as butyrate, propionate, acetate rose, but their aldehydes (butyraldehyde, acrolein, acetaldehyde decreased in oral fluid during periodontitis. The concentration of these compounds were found to be between the levels in control persons and during periodontitis. The content of pentane decreased in oral air. That depended on the intensity of inflammation and vessel disturbances. The results suggest that VSCFA produced by Porphyromonas, Prevotella, Fusobacterium and other periodontopathic bacteria, penetrate the oral mucosa and severely harm the periodontal tissue. The increase of dimethyl sulphide contributed to oral malodor during periodontal inflammation.


Internet use time and subjective well-being during the COVID-19 outbreak: serial mediation of problematic internet use and self-esteem.
The coronavirus disease (COVID-19) outbreak is a threat to adolescents' mental health and livelihoods, and lowers their subjective well-being (SWB). Expanding on previous literatures, this study examined whether internet use time was related to SWB and whether this relationship was mediated by problematic internet use (PIU) and self-esteem during the COVID-19 outbreak. In Taiwan, the COVID-19 epidemic broke out in February, 2020. During March 2 to 27, this study recruited a total of 1,060 adolescents from junior high schools by both stratified and cluster sampling, and administered a comprehensive investigation. The results displayed that SWB was significantly and negatively predicted by internet use time. PIU fully mediated the relationship. Moreover, PIU predicted a decrease of self-esteem, which played a full mediation role between PIU and SWB. The results provide evidence in explaining how increased internet use time is associated with a greater level of PIU, which relates to lower self-esteem, correlating with lower SWB in adolescents. This study can provide reference to mental health organizations and educational agencies to design appropriate SWB promotion programs for the junior high school population in terms of epidemic prevention.


An integrative study of island diversification: Insights from the endemic Haemodracon geckos of the Socotra Archipelago.
The Socotra Archipelago in the Arabian Sea is considered one of the most geo-politically isolated landforms on earth and a center of endemism. The archipelago is located at the western edge of the Indian Ocean and comprises four islands: Socotra, Darsa, Samha, and Abd al Kuri. Here we provide an integrative study on Haemodracon geckos, the sole genus of geckos strictly endemic to the archipelago. The sympatric distribution of Haemodracon riebeckii and H. trachyrhinus on Socotra Island provides a unique opportunity to explore evolutionary relationships and speciation patterns, examining the interplay between possible sympatric and allopatric scenarios. We used molecular data for phylogenetic inference, species delimitation analyses, and to infer the diversification timeframe. Multivariate statistics were used to analyze morphological data. Ecological comparisons were explored for macro-niches using species distribution models and observations were used for micro-habitat use. Haemodracon species exhibit great levels of intraspecific genetic diversity. Our calibration estimates revealed that Haemodracon diverged from its closest relative, the mainland genus Asaccus, in the Eocene, before the detachment of the archipelago. The two Haemodracon species diversified in situ on Socotra Island during the Middle Miocene, after the archipelago's isolation, into the two reciprocally monophyletic recognized species. Their divergence is associated mostly with remarkable body size differences and micro-habitat segregation, with low levels of climatic and body shape divergences within their sympatric distributions. These results display how ecological, sympatric speciation, and allopatric speciation followed by secondary contact, may both have varying roles at different evolutionary phases.


Line Operators in Chern-Simons-Matter Theories and Bosonization in Three Dimensions.
We study Chern-Simons theories at large N with either bosonic or fermionic matter in the fundamental representation. The most fundamental operators in these theories are mesonic line operators, the simplest example being Wilson lines ending on fundamentals. We classify the conformal line operators along an arbitrary smooth path as well as the spectrum of conformal dimensions and transverse spins of their boundary operators at finite 't Hooft coupling. These line operators are shown to satisfy first-order chiral evolution equations, in which a smooth variation of the path is given by a factorized product of two line operators. We argue that this equation together with the spectrum of boundary operators are sufficient to uniquely determine the expectation values of these operators. We demonstrate this by bootstrapping the two-point function of the displacement operator on a straight line. We show that the line operators in the theory of bosons and the theory of fermions satisfy the same evolution equation and have the same spectrum of boundary operators.


Cytohistologic correlation in premenopausal and postmenopausal women.
This study was conducted to compare the correlation between Pap smear and colposcopic biopsy findings in premenopausal and postmenopausal women. A total of 68,738 ThinPrep Pap smears were done in 2011 in our institution, and of these, 865 of the women (787 premenopausal and 78 postmenopausal) had subsequent colposcopic directed biopsies performed within 3 months of obtaining the results. We discovered that 52.5% of the Pap smears in postmenopausal women versus 33.6% in premenopausal women were classified as false positive (FP), with respect to the biopsy, and of these, 47.6 vs. 17% cases had no transformation zone (TZ) on the subsequent biopsies, respectively. Interestingly, with respect to high-risk human papilloma virus (hrHPV) testing in patients having both Pap smear and biopsies performed, we found the Pap smear diagnoses were a better predictor of positive hrHPV than the respective colposcopic biopsies. As many of the FP postmenopausal women had an absent TZ (47.6%) on biopsy, and because the majority (83.3%) of those which had hrHPV testing were positive, we suggest that this indicates a potential sampling error on biopsy, perhaps due to an inability to visualize the involved area in older women due to an upward migration of the TZ.


Selective loss of S-cones in diabetic retinopathy.
To determine whether selective cone loss could explain the acquired tritan-like color confusion found in diabetic retinopathy. Terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick end labeling (TUNEL) was employed on paraffin sections of retinas from 5 donors with diabetic retinopathy. For quantitative analysis, postmortem retinas were obtained from 13 human donors; 7 from patients with various durations and stages of diabetic retinopathy (4 background, 3 proliferative) and 6 controls. Enzyme histochemical analysis for carbonic anhydrase (CA) was used to distinguish L/M-cones (positive for CA) from S-cones (negative for CA). Cone topography was determined by sampling 360 degrees from 0.1 to 1.5 mm of foveal eccentricity and along the horizontal meridians from 1.5 to 15.0 mm. Rare cells in both the inner and outer nuclear layers of the diabetic eyes were positively labeled with the TUNEL method. The CA staining revealed incomplete and patchy losses of S-cones that were limited to the diabetic retinas. Statistically significant reduction in the density of S-cones was found at nearly all foveal eccentricities from 0.1 mm to 15.0 mm. This was not the case for the L/M-cones. On average, for all locations, the percentage of S-cones compared with L/M-cones was decreased by 21.0% +/- 3.4% with respect to the controls. The S-cones selectively die in diabetic retinopathy. Selective loss of S-cones may contribute to the tritan-like color vision deficit seen in patients with diabetic retinopathy.


Genetic variants in taste-related genes and risk of pancreatic cancer.
Pancreatic ductal adenocarcinoma is an aggressive and relatively rare cancer with a dismal 5-year survival rate and a clear genetic background. Genetic variants in taste receptors and taste-related genes have been associated with a variety of human traits and phenotypes among which several cancer types and pancreatic cancer risk factors. In this study, we analysed 2854 single-nucleotide polymorphisms in 50 taste-related genes, including 37 taste receptors. To cover all the genetic variability of the selected genes and to include also regulatory elements, we added 5000 nucleotides to both ends of each gene. We used a two-phase approach, with the PanScan data set (3314 cases and 3431 controls) as the discovery phase and PanC4 (3893 cases and 3632 controls) as validation phase, for a total of 7207 cases and 7063 controls. The datasets were downloaded from the NCBI database of genotypes and phenotypes (dbGaP). We observed that the taste 1 receptor member 2 (TAS1R2)-rs11261087 variant was associated with pancreatic cancer risk in both phases independently, with a consistent association of the T allele with decreased risk of developing the disease [phase 1 odds ratio (OR) = 0.89, 95% confidence interval (CI) 0.80-0.98; phase 2 OR = 0.91, 95% CI 0.83-0.99; all subjects together OR = 0.90, 95% CI 0.84-0.96, P = 0.002]. However, neither the association observed in the validation phase nor those observed in the joint analysis were statistically significant considering multiple testing. Functional studies are warranted to better understand the impact of the genetic variability of TAS1R2 on PDAC risk.


Face processing in Pervasive Developmental Disorder (PDD): the roles of expertise and spatial frequency.
Both a reduced face expertise and a basic abnormality in visual information, e.g. spatial frequency, processing have been proposed as possible causes of the abnormal face processing in Pervasive Developmental Disorder (PDD). This study investigated both the roles of expertise and spatial frequency for face processing in PDD. Event-related potentials (ERPs) and dipole sources were measured in response to (upright/inverted) high- and low-pass filtered faces, houses, and stimuli for which children with PDD were experts. ERP analyses for specific posterior electrodes showed no differences between children with PDD and matched controls, but source analyses did. These showed that controls activated specialized brain sources for the processing of faces, which was dependent on low spatial frequency content. However, children with PDD did not. Importantly, present results argue against the idea that this is due to a reduced face expertise on the part of the children with PDD, but instead support an abnormality in spatial frequency processing.


Impact of Preexisting Depression and Anxiety on Hospital Readmission and Long-Term Survival After Cardiac Arrest.
While sudden cardiac arrest (CA) survivors are at risk for developing psychiatric disorders, little is known about the impact of preexisting mental health conditions on long-term survival or postacute healthcare utilization. We examined the prevalence of preexisting psychiatric conditions in CA patients who survived hospital discharge, characterized incidence and reason for inpatient psychiatry consultation during these patients' acute hospitalizations, and determined the association of pre-CA depression and anxiety with hospital readmission rates and long-term survival. We hypothesized that prior depression or anxiety would be associated with higher hospital readmission rates and lower long-term survival. We conducted a retrospective cohort study including patients resuscitated from in- and out-of-hospital CA who survived both admission and discharge from a single hospital between January 1, 2010, and December 31, 2017. We identified patients from our prospective registry, then performed a structured chart review to abstract past psychiatric history, prescription medications for psychiatric conditions, and identify inpatient psychiatric consultations. We used administrative data to identify readmissions within 1 year and vital status through December 31, 2020. We used multivariable Cox regressions controlling for patient demographics, medical comorbidities, discharge Cerebral Performance Category and disposition, depression, and anxiety history to predict long-term survival and hospital readmission. We included 684 subjects. Past depression or anxiety was noted in 24% (n = 162) and 19% (n = 129) of subjects. A minority of subjects (n = 139, 20%) received a psychiatry consultation during the index hospitalization. Overall, 262 (39%) subjects had at least 1 readmission within 1 year. Past depression was associated with an increased hazard of hospital readmission (hazard ratio 1.50, 95% CI 1.11-2.04), while past anxiety was not associated with readmission. Neither depression nor anxiety were independently associated with long-term survival. Depression is an independent risk factor for hospital readmission in CA survivors.


Drug-induced glomerular disease: immune-mediated injury.
Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.


Structural basis for the broad specificity of a new family of amino-acid racemases.
Broad-spectrum amino-acid racemases (Bsrs) enable bacteria to generate noncanonical D-amino acids, the roles of which in microbial physiology, including the modulation of cell-wall structure and the dissolution of biofilms, are just beginning to be appreciated. Here, extensive crystallographic, mutational, biochemical and bioinformatic studies were used to define the molecular features of the racemase BsrV that enable this enzyme to accommodate more diverse substrates than the related PLP-dependent alanine racemases. Conserved residues were identified that distinguish BsrV and a newly defined family of broad-spectrum racemases from alanine racemases, and these residues were found to be key mediators of the multispecificity of BrsV. Finally, the structural analysis of an additional Bsr that was identified in the bioinformatic analysis confirmed that the distinguishing features of BrsV are conserved among Bsr family members.


Treatment of complicated and uncomplicated hypertension with nifedipine in Palestine.
It is generally agreed that short acting calcium channel blockers (CCB) as nifedipine are not safe as the reflex increase in sympathetic activity and thus, their use in hypertension (HTN) is questionable. The objective of this study was to determine the extent of utilization of short acting nifedipine in the treatment of complicated and uncomplicated HTN in one of the major districts in Palestine, Nablus. The data for this study were collected from patient's medical files. Data collection was made over a period of 6 months (April - October 2003) in Nablus, Palestine. The sample studied included 876 patients with cardiovascular diseases. Focus was made on the 262 patients with uncomplicated HTN and the 147 patients with both HTN and diabetes mellitus. A total of 247 (28.2%) patients in the study sample were receiving CCB. One third (33.7%) of patients with uncomplicated HTN were receiving CCB mainly as monotherapy with most of them (61%) were receiving the old generation nifedipine as a short acting formulation. Use of nifedipine was also more common among elderly patients above the age of 60 years. There was a tendency to use short acting nifedipine as antihypertensive monotherapy among patients with either uncomplicated or complicated HTN. This irrational use needs to be reviewed since it is associated with higher risks.


Spread of domestic animals across Neolithic western Anatolia: New stable isotope evidence from Uğurlu Höyük, the island of Gökçeada, Turkey.
The origins of agriculture in Southwest Asia over 10,000 years ago and its subsequent spread into Europe during the Neolithic have been the focus of much archaeological research over the past several decades. Increasingly more sophisticated analytical techniques have allowed for better understanding of the complex interactions that occurred amongst humans, animals, and their environments during this transition. The Aegean Islands are critically situated where Anatolia and the mainland Greece meet, making the region pivotal for understanding the movement of the Neolithic into Europe. Located on the largest Turkish Aegean island of Gökçeada, the site of Uğurlu Höyük dates to the early Neolithic and has been the subject of ongoing excavations and research integrating a rigorous dating program with comprehensive zooarchaeological research. This paper focuses on the combination of bone collagen and tooth enamel stable isotope data with existing archaeological data to develop a fine-resolution picture of the spread of the Neolithic, particularly the importation and management of domestic fauna on Gökçeada, with broader relevance for understanding Aegean-Anatolian interactions. The stable isotope values from the fauna at Uğurlu have been used for both diachronic intrasite analyses and intersite comparisons between contemporaneous mainland sites. Integrating stable isotope and zooarchaeological datasets makes Uğurlu one of the first island sites to provide a comprehensive understanding of the geographic origin of Neolithic livestock populations and the timing of their spread from Anatolia into Europe during the process of Neolithization.


Cooperative root graft networks benefit mangrove trees under stress.
The occurrence of natural root grafts, the union of roots of the same or different trees, is common and shared across tree species. However, their significance for forest ecology remains little understood. While early research suggested negative effects of root grafting with the risk of pathogen transmission, recent evidence supports the hypothesis that it is an adaptive strategy that reduces stress by facilitating resource exchange. Here, by analysing mangrove root graft networks in a non-destructive way at stand level, we show further evidence of cooperation-associated benefits of root grafting. Grafted trees were found to dominate the upper canopy of the forest, and as the probability of grafting and the frequency of grafted groups increased with a higher environmental stress, the mean number of trees within grafted groups decreased. While trees do not actively 'choose' neighbours to graft to, our findings point to the existence of underlying mechanisms that regulate 'optimal group size' selection related to resource use within cooperating networks. This work calls for further studies to better understand tree interactions (i.e. network hydraulic redistribution) and their consequences for individual tree and forest stand resilience.


Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity.
Muscular lymphatics use both phasic and tonic contractions to transport lymph for conducting their vital functions. The molecular mechanisms regulating lymphatic muscle contractions are not well understood. Based on the well-established finding that the phosphorylation of myosin light chain 20 (MLC(20)) plays an essential role in blood vessel smooth muscle contraction, we investigated if phosphorylated MLC(20) (pMLC(20)) would modulate the tonic and/or phasic contractions of lymphatic muscle. The effects of ML-7, a MLC kinase inhibitor (1-10 microM), were tested on the contractile parameters of isolated and cannulated rat mesenteric lymphatics during their responses to the known modulators, pressure (1-5 cm H(2)O) and substance P (SP; 10(-7) M). Immunohistochemical and Western blot analyses of pMLC(20) were also performed on isolated lymphatics. The results showed that 1) increasing pressure decreased both the lymphatic tonic contraction strength and pMLC(20)-to-MLC(20) ratio; 2) SP increased both the tonic contraction strength and phosphorylation of MLC(20); 3) ML-7 decreased both the lymphatic tonic contraction strength and pMLC(20)-to-MLC(20) ratio; and 4) the increase in lymphatic phasic contraction frequency in response to increasing pressure was diminished by ML-7; however, the phasic contraction amplitude was not significantly altered by ML-7 either in the absence or presence of SP. These data provide the first evidence that tonic contraction strength and phasic contraction amplitude of the lymphatics can be differentially regulated, whereby the increase in MLC(20) phosphorylation produces an activation in the tonic contraction without significant changes in the phasic contraction amplitude. Thus, tonic contraction of rat mesenteric lymphatics appears to be MLC kinase dependent.


Myositis induced by naked DNA immunization with the gene for histidyl-tRNA synthetase.
Polymyositis is regarded as an autoimmune inflammatory muscle disease. A major subgroup of patients have autoantibodies to cellular histidyl-transfer RNA synthetase (HRS). We have analyzed the role of the autoantigen HRS in the induction of murine myositis in a comparative study of inoculation of BALB/c mice with recombinant HRS protein versus naked DNA coding for HRS. Adult BALB/c mice produced antibodies to human HRS following inoculation with HRS protein and adjuvant, but myositis was not observed. Alternatively, expression plasmid DNA constructs encoding full-length and truncated human HRS were inoculated intramuscularly in gene transfer studies. DNA-inoculated mice produced relatively low anti-HRS antibody titers. However, in contrast to recombinant HRS protein-inoculated mice, HRS gene transfer induced pathology with evidence of cellular infiltration of perivascular and endomysial regions of the inoculated muscle. Multiple inoculations of a plasmid construct encoding a hybrid molecule consisting of HRS and the transferrin receptor cytoplasmic tail induced the highest levels of antibodies and persisting cellular infiltration. Unlike HRS, expression of influenza virus hemagglutinin (HA) following inoculation of an HA plasmid did not induce myositis. Transfer of naked DNA constructs expressing HRS is likely to provide valuable information on the autoimmune response to this protein and its role in the development of myositis.


Ex vivo lung perfusion review of a revolutionary technology.
Donor lung shortage has been the main reason to the increasing number of patients waiting for lung transplant. Ex vivo lung perfusion (EVLP) is widely expanding technology to assess and prepare the lungs who are considered marginal for transplantation. the outcomes are encouraging and comparable to the lungs transplanted according to the standard criteria. in this article, we will discuss the history of development, the techniques and protocols of ex vivo, and the logics and rationales for ex vivo use.


Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility.
Matrix metalloproteinases (MMPs) play an important role in tissue remodelling associated with various physiological and pathological processes, such as morphogenesis, angiogenesis, tissue repair, arthritis, chronic heart failure, chronic obstructive pulmonary disease, chronic inflammation and cancer metastasis. As a result, MMPs are considered to be viable drug targets in the therapy of these diseases. Despite the high therapeutic potential of MMP inhibitors (MMPIs), all clinical trials have failed to date, except for doxycycline for periodontal disease. This can be attributed to (i) poor selectivity of the MMPIs, (ii) poor target validation for the targeted therapy and (iii) poorly defined predictive preclinical animal models for safety and efficacy. Lessons from previous failures, such as recent discoveries of oxidative/nitrosative activation and phosphorylation of MMPs, as well as novel non-matrix related intra- and extracellular targets of MMP, give new hope for MMPI development for both chronic and acute diseases. In this article we critically review the major structural determinants of the selectivity and the milestones of past design efforts of MMPIs where 2-/3-dimensional structure-based methods were intensively applied. We also analyse the in vitro screening and preclinical/clinical pharmacology approaches, with particular emphasis on drawing conclusions on how to overcome efficacy and safety problems through better target validation and design of preclinical studies.


The involvement of protein kinase A in the immune response of Galleria mellonella larvae to bacteria.
The role of protein kinase A (PKA) in the humoral immune response of the greater wax moth Galleria mellonella larvae to live gram-positive bacteria Micrococcus lysodeikticus and gram-negative bacteria Escherichia coli was investigated. The immune challenge of larvae with both kinds of bacteria caused an increase in fat body PKA activity depending on the injected bacteria. Gram-positive M. lysodeikticus was a much better inducer of the enzyme activity than gram-negative E. coli. The PKA activity was increased about 2.5-fold and 1.5-fold, after M. lysodeikticus and E. coli injection, respectively. The in vivo inhibition of the enzyme activity by a cell permeable selective PKA inhibitor, Rp-8-Br-cAMPS, was correlated with considerable changes of fat body lysozyme content and hemolymph antimicrobial activity in bacteria-challenged insects. The kinetics of changes were different and dependent on the bacteria used for the immune challenge of G. mellonella larvae.


Substrate-induced conformational changes in the essential peripheral membrane-associated mannosyltransferase PimA from mycobacteria: implications for catalysis.
Phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential glycosyltransferase (GT) involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), which are key components of the mycobacterial cell envelope. PimA is the paradigm of a large family of peripheral membrane-binding GTs for which the molecular mechanism of substrate/membrane recognition and catalysis is still unknown. Strong evidence is provided showing that PimA undergoes significant conformational changes upon substrate binding. Specifically, the binding of the donor GDP-Man triggered an important interdomain rearrangement that stabilized the enzyme and generated the binding site for the acceptor substrate, phosphatidyl-myo-inositol (PI). The interaction of PimA with the beta-phosphate of GDP-Man was essential for this conformational change to occur. In contrast, binding of PI had the opposite effect, inducing the formation of a more relaxed complex with PimA. Interestingly, GDP-Man stabilized and PI destabilized PimA by a similar enthalpic amount, suggesting that they formed or disrupted an equivalent number of interactions within the PimA complexes. Furthermore, molecular docking and site-directed mutagenesis experiments provided novel insights into the architecture of the myo-inositol 1-phosphate binding site and the involvement of an essential amphiphatic alpha-helix in membrane binding. Altogether, our experimental data support a model wherein the flexibility and conformational transitions confer the adaptability of PimA to the donor and acceptor substrates, which seems to be of importance during catalysis. The proposed mechanism has implications for the comprehension of the peripheral membrane-binding GTs at the molecular level.


Otoscopy, rhinoscopy, and bronchoscopy in small animal clinics.
Otoscopy, rhinoscopy, and bronchoscopy are indispensable techniwues in ear, nose, and throat clinics and in diseases of the trachea and the bronchial tree. The quality of the instruments used in these techniques is of primary importance. The endoscopic procedures, the instruments used, and the indications for the examinations are discussed.


[A comparative assessment of the life quality of patients after various surgeries because of complicated duodenal ulcer].
Showings of studying the life quality with the aid of the SF-36 questionnaire can be used for assessing long-term results of various types of surgeries at complicated duodenal ulcer. Unlike stomach resections, functional surgeries provide a higher life quality of patients. Such differences become more apparent as time after the surgery passes by.


Prognostic Significance of Transitional Cell Carcinoma-Like Morphology of High-Grade Serous Ovarian Carcinoma: A Comparative Study.
This was a retrospective population-based study investigating the demographic characteristics, clinical characteristics, and prognosis of patients with ovarian high-grade serous carcinoma displaying transitional cell carcinoma-like (TC-like) morphological features. A cohort of patients diagnosed with ovarian high-grade serous carcinoma from 1988 to 2012 was drawn from the National Cancer Institute's Surveillance Epidemiology and End Results Database. Patients with transitional cell histology were included in the study group, whereas patients with other serous tumors served as controls. Demographic and clinical characteristics between the study and the control groups were compared using χ test. For surgically treated patients, survival was estimated by generation of Kaplan-Meier curves. Multivariate analysis was performed using the Cox regression method. A total of 29,716 patients met the inclusion criteria. From these, 264 patients (0.9%) were included in the TC-variant group, whereas 29,452 (99.1%) composed the control group. Patients with TC-variant tumors were younger and more likely to present with larger, unilateral tumors at an early disease stage. Surgically treated patients with advanced stage had a median disease-specific survival of 50 months compared with 40 months in the control group (P = 0.013). In that group, multivariate analysis confirmed that TC-like morphological features were an independent predictor of survival. High-grade serous carcinoma with TC-like morphological features was associated with unique demographic and clinical characteristics. For patients with advanced stage-disease, the presence of TC-like morphological features was associated with a superior survival.


The association of circulating monocyte count with coronary collateral growth in patients with diabetes mellitus.
The status of inflammation may affect the collateral development in patients with diabetes mellitus (DM). Monocytes were found to have an important role in collateral growth in animal studies. We aimed to investigate the possible association of circulating monocyte count with collateral development in patients with DM and severe coronary artery disease (CAD). We enrolled 134 consecutive patients with DM who had > or =95 stenosis in at least one major coronary artery and investigated the relationship between circulating monocyte count and collateral growth. When we analyzed the coronary angiograms of eligible patients, we found that 64 of them had good collateral growth and 70 had poor collateral growth according to the Cohen-Rentrop method. The monocyte count was significantly different between good and poor collateral growth groups (643 +/- 184 vs. 479 +/- 143 per mm(3), P < 0.001). In the analysis comparing the Rentrop score with the Gensini score and circulating monocyte count, we found significant correlations (r = 0.293, P = 0.001 and r = 0.455, P < 0.001, respectively). The duration of ischemic symptoms tended to be longer in the good collateral group (1.9 +/- 4.1 vs. 0.8 +/- 1.3 years, P = 0.079). The Gensini score was also correlated with the duration of myocardial ischemic symptoms (r = 0.299, P = 0.004). Multivariate analysis revealed an increased monocyte count in the good collateral group [odds ratio (OR), 5.726; 95% confidence interval (CI), 1.817-18.040, P = 0.003, the cut-off value for monocyte was defined as 550 cell/mm(3)]. The increased circulating monocyte count in diabetic patients was evidently related to good coronary collateral growth. This finding may be potentially important in clinical and basic cardiovascular medicine.


HIV seroprevalence amongst pregnant women in northeastern Zaire.
To assess the seroprevalence of HIV in pregnant women in northeastern Zaire and factors that correlate with seropositivity, sequential blood sampling and interviews were performed on 700 women at antenatal clinics in northeastern Zaire. The seroprevalence of the 3 clinics surveyed varied from 0.3%-5.5%, rates being higher in more urban areas. Seropositivity was associated with greater education (P<0.001) and having a partner whose job involved travelling (P<0.001). No correlation was found with marital status, age, or gravidity. Women in northeastern Zaire are at a greater risk of being infected with HIV if they are well educated or have a husband who travels due to his work. Health education on HIV should be particularly directed at women who are well educated and at men who have 'mobile' jobs.


Associations of antifolate resistance in vitro and point mutations in dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum.
Antifolate antimalarials like sulfadoxine-pyrimethamine are used as second-line treatment for Plasmodium falciparum malaria patients who fail to respond to chloroquine. The efficacy of the sulfa-pyrimethamine combination in the treatment is also compromised by the development of resistance in the parasite. Resistance to these drugs has been shown to encode with point mutations in dihydrofolate reductase and dihydropteroate synthetase genes. An experimental study. Forty clinical isolates collected from different geographical locations in India were used to assess the relationships between resistance to sulfadoxine-pyrimethamine (SP) and mutations in P. falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In vitro drug susceptibility and mutation-specific polymerase chain reaction (PCR) assays were also done. It was observed that a number of isolates possessed mutant genotypes and showed low sensitivity to SP in vitro. Of the 40 clinical isolates studied, 87.5% had DHFR and 15% had DHPS gene mutations. As observed from PCR results, 55( (22/40) presented double mutation of DHFR Arg-59 and Asn-108 and 32.5 % (13/40) had single mutant type allele of Asn-108. Of the 40 isolates, 10 % (4/40) presented doubly mutated forms of DHPS Phe-436 and Thr-613 and single mutant type allele Gly-581 was detected in 5 % (2/40) isolates. Parasites carrying double or single mutant forms of DHFR/DHPS showed elevated minimum inhibitory concentration (MIC) values of both pyrimethamine (760-6754 nM; r=0.69) and sulfadoxine (108 - 540 micro M; r=0.87) when compared to sensitive and resistant strains. Though there was a correlation between molecular techniques and in vitro drug sensitivity profiles, the relevance of these findings to the clinical efficacy of SP combination drugs needs to be established by controlled clinical trials.


Melodic sound enhances visual awareness of congruent musical notes, but only if you can read music.
Predictive influences of auditory information on resolution of visual competition were investigated using music, whose visual symbolic notation is familiar only to those with musical training. Results from two experiments using different experimental paradigms revealed that melodic congruence between what is seen and what is heard impacts perceptual dynamics during binocular rivalry. This bisensory interaction was observed only when the musical score was perceptually dominant, not when it was suppressed from awareness, and it was observed only in people who could read music. Results from two ancillary experiments showed that this effect of congruence cannot be explained by differential patterns of eye movements or by differential response sluggishness associated with congruent score/melody combinations. Taken together, these results demonstrate robust audiovisual interaction based on high-level, symbolic representations and its predictive influence on perceptual dynamics during binocular rivalry.


The new history of psychology II: Some (different) answers to Watrin's four questions.
This article is mainly a response to the article by João Paulo Watrin, "The Ambiguous 'New History of Psychology': Some New Questions to Brock (2017)" (Watrin, 2017), which was itself a reply to my article, "The New History of Psychology: Some (Different) Answers to Lovett's Five Questions" (Brock, 2017). Watrin (2017) suggested that previous writers have conflated the terms "critical history" and "new history." They are said to differ, in that although the former is merely a name for a loose collection of approaches to the history of psychology, the latter involves rhetoric about the historiographical commitments of critical history. He also disputed the validity of the distinction between "old" and "new" history. I suggest that he is wrong on all these points. Watrin then poses and answers four rhetorical questions on Whig history, textbooks, critical thinking, and ad hominem arguments, and I provide alternative answers to all of them. After suggesting that our different views can be attributed to different agendas, I conclude with some reflections on how professional historians and psychologists can work together. (PsycINFO Database Record


Knowledge and attitudes in Puerto Rico concerning dengue prevention.
Dengue has been endemic in Puerto Rico for three decades. Multiple educational and community-based efforts have been developed to inform the population about dengue prevention. We undertook this study to understand the community members' knowledge, attitudes, and practices related to dengue prevention and to elicit their ideas for future prevention campaigns. A qualitative study based on grounded theory analysis was conducted between February and May of 2001. The study involved a total of 34 participants in four group interviews who had been identified through the Puerto Rico dengue surveillance system. In general, participants had correct knowledge about dengue prevention, but they did not associate the mosquitoes inside their houses with Aedes aegypti. Participants insisted that "neighbors" needed to control larval habitats, and the participants also asked the Government to fumigate. The patterns of knowledge and opinion that emerged in the discussions can be arranged along an axis going from high levels of correct knowledge to low levels of correct knowledge about dengue and dengue hemorrhagic fever and related practices. There were few participants at either extreme. Three themes explained these patterns: misconceptions about dengue (based on previously delivered information), the "invisibility" of dengue (as compared to other diseases), and responsibility (individual and Government). Four strategies for preventive behaviors were recommended: developing community groups to identify community priorities on prevention, developing volunteer groups to deliver prevention messages, making house visits to demonstrate specific control measures, and conducting a complementary media campaign to support these strategies.


Vascular risk factors: imaging and neuropathologic correlates.
Cerebrovascular disease plays an important role in cognitive disorders in the elderly. Cerebrovascular disease and Alzheimer's disease interact on several levels, with one important level being the overlap in risk factors. The major vascular risk factors such as diabetes and impaired glycemic control, hypertension, obesity, and hyper- or dyslipidemia have been associated both with Alzheimer's disease and vascular dementia. The purpose of this review is to consider the context in which vascular dementia is diagnosed, place the pathophysiological consequences of cerebrovascular disease on cognition in the context of clinical and pathological Alzheimer's disease, and then to consider the evidence for the role of major vascular risk factors in late-life cognitive impairment, changes in brain imaging and neuropathological changes. Midlife diabetes mellitus, hypertension, and obesity are established risk factors for clinically defined Alzheimer's disease as well as vascular dementia. The basis for these relationships could either be that the risk factors lead to microvascular brain disease, promote Alzheimer pathology or both. The associations of late-life onset diabetes mellitus, hypertension, and obesity with cognitive impairment are either attenuated or reversed. The role of vascular risk factors in midlife should be the focus of public health efforts to reduce the burden of late-life cognitive impairment.


Technical Note: Proof of concept for radiomics-based quality assurance for computed tomography.
Routine quality assurance (QA) testing to identify malfunctions in medical imaging devices is a standard practice and plays an important role in meeting quality standards. However, current daily computed tomography (CT) QA techniques have proven to be inadequate for the detection of subtle artifacts on scans. Therefore, we investigated the ability of a radiomics phantom to detect subtle artifacts not detected in conventional daily QA. An updated credence cartridge radiomics phantom was used in this study, with a focus on two of the cartridges (rubber and cork) in the phantom. The phantom was scanned using a Siemens Definition Flash CT scanner, which was reported to produce a subtle line pattern artifact. Images were then imported into the IBEX software program, and 49 features were extracted from the two cartridges using four different preprocessing techniques. Each feature was then compared with features for the same scanner several months previously and with features from controlled CT scans obtained using 100 scanners. Of 196 total features for the test scanner, 79 (40%) from the rubber cartridge and 70 (36%) from the cork cartridge were three or more standard deviations away from the mean of the controlled scan population data. Feature values for the artifact-producing scanner were closer to the population mean when features were preprocessed with Butterworth smoothing. The feature most sensitive to the artifact was co-occurrence matrix maximum probability. The deviation from the mean for this feature was more than seven times greater when the scanner was malfunctioning (7.56 versus 1.01). Radiomics features extracted from a texture phantom were able to identify an artifact-producing scanner as an outlier among 100 CT scanners. This preliminary analysis demonstrated the potential of radiomics in CT QA to identify subtle artifacts not detected using the currently employed daily QA techniques.


3D Lithiophilic CuZrAg Metallic Glass Based-Current Collector for High-Performance Lithium Metal Anode.
Lithium metal anodes face several challenges in practical applications, such as dendrite growth, poor cycle efficiency, and volume variation. 3D hosts with lithiophilic surfaces have emerged as a promising design strategy for anodes. In this study, inspiration from the intrinsic isotropy, chemical heterogeneity, and wide tunability of metallic glass (MG) is drew to develop a 3D mesoporous host with a lithiophilic surface. The CuZrAg MG is prepared using the scalable melt-spinning technique and subsequently treated with a simple one-step chemical dealloying method. This resultes in the creation of a host with a homogeneously distributed abundance of lithium affinity sites on the surface. The excellent lithiophilic property and capability for uniform lithium deposition of the 3D CuZrAg electrode have been confirmed through theoretical calculations. Therefore, the 3D CuZrAg electrode displays excellent cyclic stability for over 400 cycles with 96% coulomb efficiency, and ultra-low overpotentials of 5 mV for over 2000 h at 1.0 mA cm-2 and 1.0 mAh cm-2 . Additionally, the full cells partied with either LiFePO4 or LiNi0.8 Co0.1 Mn0.1 O2 cathode deliver exceptional long-term cyclability and rate capability. This work demonstrates the great potential of metallic glass in lithium metal anode application.