Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults.
Autism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism. Brain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli. In controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical. Overall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.


Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats.
During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type.


Comparative Analysis of the miRNome of Bovine Milk Fat, Whey and Cells.
Abundant miRNAs have been identified in milk and mammary gland tissues of different species. Typically, RNA in milk can be extracted from different fractions including fat, whey and cells and the mRNA transcriptome of milk could serve as an indicator of the transcriptome of mammary gland tissue. However, it has not been adequately validated if the miRNA transcriptome of any milk fraction could be representative of that of mammary gland tissue. The objectives of this study were to (1) characterize the miRNA expression spectra from three milk fractions- fat, whey and cells; (2) compare miRNome profiles of milk fractions (fat, whey and cells) with mammary gland tissue miRNome, and (3) determine which milk fraction miRNome profile could be a better representative of the miRNome profile of mammary gland tissue. Milk from four healthy Canadian Holstein cows in mid lactation was collected and fractionated. Total RNA extracted from each fraction was used for library preparation followed by small RNA sequencing. In addition, miRNA transcripts of mammary gland tissues from twelve Holstein cows in our previous study were used to compare our data. We identified 210, 200 and 249 known miRNAs from milk fat, whey and cells, respectively, with 188 universally expressed in the three fractions. In addition, 33, 31 and 36 novel miRNAs from milk fat, whey and cells were identified, with 28 common in the three fractions. Among 20 most highly expressed miRNAs in each fraction, 14 were expressed in common and 11 were further shared with mammary gland tissue. The three milk fractions demonstrated a clear separation from each other using a hierarchical cluster analysis with milk fat and whey being most closely related. The miRNome correlation between milk fat and mammary gland tissue (rmean = 0.866) was significantly higher than the other two pairs (p < 0.01), whey/mammary gland tissue (rmean = 0.755) and milk cell/mammary gland tissue (rmean = 0.75), suggesting that milk fat could be an alternative non-invasive source of RNA in assessing miRNA activities in bovine mammary gland. Predicted target genes (1802) of 14 highly expressed miRNAs in milk fractions were enriched in fundamental cellular functions, infection, organ and tissue development. Furthermore, some miRNAs were highly enriched (FDR <0.05) in milk whey (3), cells (11) and mammary gland tissue (14) suggesting specific regulatory functions in the various fractions. In conclusion, we have obtained a comprehensive miRNA profile of the different milk fractions using high throughput sequencing. Our comparative analysis showed that miRNAs from milk fat accurately portrayed the miRNome of mammary gland tissue. Functional annotation of the top expressed miRNAs in milk confirmed their critical regulatory roles in mammary gland functions and potentially to milk recipients.


Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells.
This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using 1H-NMR-based metabolome analysis, we showed the metabolic effect of piperine on skeletal muscle and found that piperine increased the level of intracellular lactate, an important metabolic intermediate that controls expression of several genes involved in mitochondrial activity. Piperine also induced the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target, acetyl-CoA carboxylase (ACC), while additionally stimulating glucose uptake in an AMPK dependent manner. Piperine also stimulates the p38 mitogen-activated protein kinase (p38 MAPK), an effect that was reversed by pretreatment with compound C, an AMPK inhibitor. Inhibition of p38 MAPK resulted in no piperine-induced glucose uptake. Increased level of lactate resulted in increased expression of mitochondrial uncoupling protein 1 (UCP1), which regulates energy expenditure, thermogenesis, and fat browning. Knock-down of AMPK blocked piperine-induced UCP1 up-regulation, demonstrating the required role of AMPK in this effect. Taken together, these results suggest that piperine leads to benign metabolic effects by activating the AMPK-p38 MAPK signaling pathway and UCP1 expression by activating intracellular lactate production in skeletal muscle.


Laparoscopic-assisted Malone appendicostomy in the management of fecal incontinence in children.
The antegrade continence enema procedure offers convenient enema administration for patients with fecal incontinence and can be performed by a minimally invasive approach that provides shorter hospital stay, less analgesia requirement, and better cosmesis. We present our experience using this approach for fecal incontinence patients and technical modifications to reduce complications. Following successful management of fecal incontinence through bowel management using a daily rectal enema, 44 patients underwent a laparoscopic-assisted Malone appendicostomy procedure. We reviewed the diagnosis underlying the fecal incontinence, operative technique, duration of surgery, length of hospital stay, and postoperative complications. The mean age at surgery was 8.6 ± 1.0 years. The diagnoses included anorectal malformations (31), idiopathic constipation (6), Hirschsprung disease (3), and others (4). All the patients underwent a V-V umbilico-appendicoplasty. The cecum was plicated around the base of the appendix in 34 patients (77%); this step was omitted in 10 (23%). The median follow-up was 21 months (range: 3-51 months). Twelve complications were recorded in 9 patients (20.5%)--leakage from the stoma in 1 (2.3%), stomal stenosis in 5 (11.4%), and a combination of both in 3 (6.8%)--with an overall stricture rate of 18.2% (8/44) and leakage rate of 9.1% (4/44). Strictures were managed with minor operative revision. Plicating the cecum was associated with a lower leakage rate compared with the nonplicated group (0/34, 0% versus 4/10, 40%; P = .002). All patients were consistently clean between enemas following their antegrade continence enema procedure. The umbilical appendicostomy provides a convenient and cosmetic location for enema administration. Cecal plication, which is feasible using a laparoscopic-assisted approach, significantly reduces the leakage rate. Stomal stenoses remains a problem, may be lessened by a V-to-V umbilical to appendix anastomosis, and are easily fixed with a revision.


Improving alginate printability for biofabrication: establishment of a universal and homogeneous pre-crosslinking technique.
Many different biofabrication approaches as well as a variety of bioinks have been developed by researchers working in the field of tissue engineering. A main challenge for bioinks often remains the difficulty to achieve shape fidelity after printing. In order to overcome this issue, a homogeneous pre-crosslinking technique, which is universally applicable to all alginate-based materials, was developed. In this study, the Young's Modulus after post-crosslinking of selected hydrogels, as well as the chemical characterization of alginate in terms of M/G ratio and molecular weight, were determined. With our technique it was possible to markedly enhance the printability of a 2% (w/v) alginate solution, without using a higher polymer content, fillers or support structures. 3D porous scaffolds with a height of around 5 mm were printed. Furthermore, the rheological behavior of different pre-crosslinking degrees was studied. Shear forces on cells as well as the flow profile of the bioink inside the printing nozzle during the process were estimated. A high cell viability of printed NIH/3T3 cells embedded in the novel bioink of more than 85% over a time period of two weeks could be observed.


Emendation of genus Collinsella and proposal of Collinsella stercoris sp. nov. and Collinsella intestinalis sp. nov.
Collinsella aerofaciens-like strains isolated from human faeces were characterized by biochemical tests, cell wall murein analysis and 16S rDNA analysis. The results indicated that these strains are phylogenetically a member of the family Coriobacteriaceae and close to the genus Collinsella. Their phenotypic characters resembled those of Collinsella aerofaciens. Determination of DNA-DNA relatedness showed that these strains could be divided into two groups (groups 1 and 2). Collinsella aerofaciens and both new groups have A4-type cell wall murein. Based on their phenotypic and phylogenetic characters, two new species of the genus Collinsella are proposed for the isolated strains: Collinsella stercoris for group 1 and Collinsella intestinalis for group 2. Species-specific PCR primer sets for these two species were also constructed. Using these primer sets, Collinsella stercoris and Collinsella intestinalis can be identified easily and rapidly.


Relationship between spermatozoan lipid composition and fertility during aging of chickens.
Changes in the proportions of the various lipid components in spermatozoa were investigated throughout the reproductive period (24-72 wk of age) of male chickens. Sperm motility and in vivo fertility were also measured, and correlation coefficients with the lipid values were determined. The proportion of total phospholipid (PL) increased to reach a maximum value at 39 wk and decreased significantly thereafter. The relative content of free cholesterol and triacylglycerols showed no change in spermatozoa during aging or in relation to fertility values; free fatty acids and cholesterol esters increased continuously with age. Of the various PL classes, phosphatidylserine and phosphatidylcholine displayed a pattern of changes with age positively and negatively, respectively, in relation to the changes of fertility. The proportion of phosphatidylethanolamine had significantly decreased by the end of the reproductive period. The proportions of C16:0, C18:0, and C18:1n-9 within the PL of the spermatozoa increased with age, and those of C20:4n-6, C22:4n-6, and C22:6n-3 decreased. Positive correlations were found between fertility and total PLs, phosphatidylserine, and PL-bound C20:4n-6 and C22:4n-6; a negative correlation was found between fertility and phosphatidylcholine. Motility was positively correlated with the level of PL and negatively with that of free cholesterol; it was also positively correlated with the levels of C22:4n-6 and C22:6n-3 and negatively with those of C16:0, C18:0, and C18:1n-9. The results suggest that the lipid and fatty acid compositions of spermatozoa may be important predictors of fertility.


Long-term efficacy of topical minoxidil in male pattern baldness.
A 24-month clinical trial, begun on a double-blind basis, was conducted in 153 men with discernible male pattern baldness of the crown with the use of either topically applied placebo, 2% minoxidil, or 3% minoxidil solution. After 4 months the patients using placebo were switched to 3% minoxidil solution. At 12 months, there were statistically significant increases in terminal hair growth within a 1-inch target area in those treated with 2% or 3% minoxidil solution, in comparison with baseline counts. However, there were few patients who had appreciable cosmetic restoration. At 12- and 24-month intervals, progressive regression or stabilization of the size of the bald area was noted in the majority of patients. This therapeutic or preventive effect was statistically significant. The data on actual target area hair counts suggested that the 2% minoxidil solution was equal to or more efficacious than the 3% minoxidil solution. Baseline vital signs and laboratory parameters remained essentially unchanged. Topical minoxidil was well tolerated, with no serious drug-related adverse reactions noted during the study.


Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor).
Sorghum (Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ∼5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ∼33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles.


Chondroectodermal dysplasia: a rare syndrome.
Chondroectodermal dysplasia (Ellis-Van Creveld syndrome) is a rare autosomal recessive congenital abnormality. This syndrome is characterized by a spectrum of clinical findings, among which chondrodystrophy, polydactyly, ectodermal dysplasia, and congenital cardiac anomalies are the most common. It is imperative to not overlook the cardiac complications in patients with this syndrome during dental procedures. The case presented here, although quite rare, was detected under normal conditions and can be alarming for dental care providers. Clinical reports outline the classical and unusual oral and dental manifestations, which help health care providers diagnose chondroectodermal dysplasia, and refer patients with this syndrome to appropriate health care professionals to receive treatment to prevent further cardiac complications and bone deformities.


Increased expression of zinc finger protein 267 in non-alcoholic fatty liver disease.
Hepatocellular lipid accumulation is a hallmark of non-alcoholicfatty liver disease (NAFLD), which encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and ultimately cirrhosis. Zinc finger protein 267 (ZNF267) belongs to the family of Kruppel-like transcription factors, which regulate diverse biological processes that include development, proliferation, and differentiation. We have previously demonstrated that ZNF267 expression is up-regulated in liver cirrhosis and is further increased in hepatocellular carcinoma (HCC). Here, we analyzed the expression of ZNF267 in tissue specimens of NAFLD patients and found a significant up-regulation compared to normal liver tissue. Noteworthy, ZNF267 mRNA was already significantly increased in steatotic liver tissue without inflammation. In line with this, incubation of primary human hepatocytes with palmitic acid induced a dose-dependent lipid accumulation and corresponding dose-dependent ZNF267 induction in vitro. Furthermore, hepatocellular lipid accumulation induced formation of reactive oxygen species (ROS), and also chemically induced ROS formation increased ZNF267 mRNA expression. In summary with previous findings, which revealed ZNF267 as pro-fibrogenic and pro-cancerogenic factor in chronic liver disease, the present study further suggests ZNF267 as promising therapeutic target particularly for NAFLD patients. In addition, it further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign.


[Phenomenology of behavior and unusual mental states of operators during forced wakefulness].
This paper presents the results of studying the functional state and mental performance of operators during three sleepless days when they worked in a highly motivated manner. It describes the phenomenology of behavior and variations of psychic states as a function of the experimental time. It gives a general characterization of asomnia-induced changes in operator's state. It discusses the effect of individual features of the psychic status of man on his tolerance of extended forced vigilance and reliability as an operator.


A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity.
Childhood absence epilepsy (CAE) is considered to exhibit a complex non-Mendelian pattern of inheritance. So far, only few CAE susceptibility genes have been identified. In a previous study of our group, an association between the GABA(A) receptor beta3 subunit (GABRB3) gene and CAE was shown. To further investigate this association, we screened 45 CAE patients of the first study for mutations in the 10 exons, the exon-intron boundaries and the regulatory sequences of GABRB3. Although we found no functionally relevant mutation, we did identify 13 single nucleotide polymorphisms (SNPs) in the GABRB3 gene region from the exon 1a promoter to the beginning of intron 3. Using these SNPs we defined four haplotypes for the respective GABRB3 gene region. A transmission disequilibrium test in the same 45 CAE patients and their parents indicated a significant association of this region and CAE (P=0.007075). Reporter gene assays in NT2 cells using exon 1a promoter constructs indicated that the disease-associated haplotype 2 promoter causes a significantly lower transcriptional activity than the haplotype 1 promoter that is over-represented in the controls. In silico analysis suggested that an exchange from T (haplotype 1) to C (haplotype 2) within this promoter impairs binding of the neuron-specific transcriptional activator N-Oct-3. Electrophoretic mobility shift assays demonstrated that the respective polymorphism reduces the nuclear protein binding affinity, thus explaining the results of the reporter gene assays. Reduced expression of the GABRB3 gene could therefore be one potential cause for the development of CAE, pathogenetically relevant in our patient group.


[The role of the system of superoxide radical formation and detoxication in the mechanism of the antineoplastic effect of adriamycin].
The intensity of formation of superoxide radicals (O(-2)) and superoxide dismutase (SOD) activity in the tissue of two transplantable gliomas were examined. The cells of these tumors were marked by unbalance between the intensity of O(-2) formation by nuclear membranes and their detoxication of SOD. This unbalance was particularly demonstrable in glioma 35 which was marked by rapid growth and high sensitivity to adriamycin. Slow-growing glioma was noted for higher activity of SOD and was insensitive to adriamycin. Since it is known that anthracycline antibiotics raise the intensity of the formation of free oxygen radicals in tumor cells, the data obtained suggest that the intensity of formation and detoxication of O(-2) may be used for the assessment of the sensitivity to these drugs.


Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.
Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates. To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response. Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay. Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins. The increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.


Salivary Cortisol Reactivity in Preterm Infants in Neonatal Intensive Care: An Integrative Review.
Recently, more and more researchers have been using salivary cortisol reactivity to evaluate stress in preterm infants in the neonatal intensive care unit (NICU). The aim of this integrative literature review was to summarize the evidence of interventions leading to a change in salivary cortisol from the baseline in preterm infants in the NICU. The electronic databases of PubMed, CINAHL, Web of Science, and Scopus were searched for relevant studies. The inclusion criteria were studies with preterm infants exposed to an intervention evaluated by salivary cortisol reactivity before discharge from the NICU, which were published in English. In total, 16 studies were included. Eye-screening examination and heel lance provoked an increase in the salivary cortisol level. Music, prone position, and co-bedding among twins decreased the salivary cortisol level. Several studies reported a low rate of successful saliva sampling or did not use control groups. Future studies need to focus on non-painful interventions in order to learn more about salivary cortisol regulation in preterm infants. Moreover, these studies should use study designs comprising homogenous gestational and postnatal age groups, control groups, and reliable analysis methods that are able to detect cortisol in small amounts of saliva.


Social support, adherence to Mediterranean diet and physical activity in adults: results from a community-based cross-sectional study.
There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support (P = 0·009) and social network support (P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet.


Person-Centered Profiles Among Treatment-Seeking Children and Adolescents with Anxiety Disorders.
Latent profile analysis (LPA) was used to derive homogeneous subgroups within the Child/Adolescent Anxiety Multimodal Study sample (N = 488; 7-17 years, M = 10.69, SD = 2.80) and examine whether class membership predicted or moderated treatment response. Subgroups were identified on baseline multi-informant measures of variables most consistently associated with outcome (youth anxiety/diagnosis, impairment, family psychopathology/functioning). Subgroup membership was examined as a predictor/moderator of outcome across the four treatment conditions (CBT, Sertraline, CBT+Sertraline, pill placebo) at posttreatment (12 weeks) and open-extension follow-up (24 weeks). Four subgroups emerged: mild symptoms/impairment, moderate symptoms/impairment, moderate symptoms/impairment with family dysfunction/parental psychopathology, and severe symptoms/impairment. There were significant between-class differences on socioeconomic status (SES; lower reported SES in the moderate with family dysfunction/parental psychopathology class compared to the mild and moderate class) and age (older age in the severe symptoms class compared to the other three classes). Youth in the mild symptoms/impairment class showed lower posttreatment anxiety across conditions but reported significantly lower symptom severity at baseline. Controlling for demographic differences, response to treatment type did not differ across classes. Analyses indicate that elevated family dysfunction/parental psychopathology clusters primarily within one subgroup of anxious youth rather than mapping onto symptom severity, highlighting the utility of LPA for clarifying within-person combinations of predictor/moderator variables. Implications for development of interventions targeting class-relevant variables are discussed.


A pore-scale reactive transport modeling study for quorum sensing-driven biofilm dispersal in heterogeneous porous media.
Microorganisms regulate the expression of energetically expensive phenotypes via a collective decision-making mechanism known as quorum sensing (QS). This study investigates the intricate dynamics of biofilm growth and QS-controlled biofilm dispersal in heterogeneous porous media, employing a pore-scale reactive transport modeling approach. Model simulations carried out under various fluid flow conditions and biofilm growth scenarios reveal that QS processes are influenced not only by the biomass density of biofilm colonies but also by a complex interplay between pore architecture, flow velocity, and the rates of biofilm growth and dispersal. This study demonstrates that pore architecture controls the initiation of QS processes and advection gives rise to oscillatory growth of biofilms. Such oscillation is suppressed if biofilm dynamics are in favor of sustaining a sufficiently high signal concentration, such as fast growth or slow dispersal rates. By establishing a mathematical framework, this study contributes to the fundamental understanding of QS-controlled biofilm dynamics in natural porous media.


Through-electromigration: a new method of investigating pore connectivity and obtaining formation factors.
The retardation of radionuclides and other contaminants in fractured crystalline rock is strongly associated with the diffusive properties of the rock matrix. At present, the scientific community is divided concerning the question of long-range pore connectivity in intrusive igneous rock. This paper presents a fast new method, called the through-electromigration method, of obtaining formation factors and investigating pore connectivity. The method involves the migration of an ionic tracer through a rock sample with an electrical potential gradient as the main driving force. The method is analogous to the through-diffusion method but the experimental time is reduced by orders of magnitude. This enables investigations of pore connectivity, as measurements can be made on longer samples. In a preliminary investigation, the new method is compared to the traditional through-diffusion method as well as to rock resistivity methods. The diffusive properties of nine granitic rock samples from Laxemar in Sweden, ranging from 15 to 121 mm in length, have been investigated and the results are compared.


Cyclooxygenase-mediated prostaglandin F2alpha is decreased in an elderly population treated with low-dose aspirin.
Low-dose aspirin (acetylsalicylic acid) is used as prophylaxis against cardiovascular diseases. The effect of aspirin on inflammation and oxidative stress, processes known to be involved in cardiovascular diseases, are not fully known. The cyclooxygenase(COX)-mediated inflammatory indicator prostaglandin F2alpha (PGF2alpha) (15-keto-dihydro-PGF2alpha), cytokine-mediated inflammatory indicators (interleukin-6, high-sensitivity C-reactive protein, serum amyloid A protein), and oxidative stress indicators (8-iso-PGF2alpha, tocopherols) were quantified in men with daily 75 mg of aspirin (n=175) and control men (n=464), all of age 77, in a cross-sectional study. Men treated with aspirin had decreased levels of urinary 15-keto-dihydro-PGF2alpha than controls (P<0.01), independent of possible cardiovascular risk factors. Aspirin-treated men had increased levels of alpha-tocopherol than controls (P<0.05). This is the first study to indicate that low-dose aspirin treatment is associated with decreased levels of PGF2alpha. This observation suggests a possible COX-mediated anti-inflammatory effect of low-dose aspirin, which should be further confirmed by intervention studies.


Anatomy of arteries and veins of submandibular glands.
Transplanting a vascularized autologous submandibular gland (SMG) is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in the blood vessels of SMG. The present study aimed to investigate the submandibular glands at the microanatomy level. The microanatomy of blood vessels including arteries and veins of submandibular gland was investigated using 30 adult corpses and 60 submandibular glands were anatomized under a surgical microscope. The lengths and diameters of the arterial and venous glandular branches were measured using sliding caliper. The submandibular gland was mainly supplied by the facial artery and submental artery, partly by the lingual artery and external jugular artery. The venous drainage of the submandibualr gland occurred through the anterior facial vein, the venae comitantes of facial artery, the vein close to the Whaston's duct (the hilum vein), and seldom drained to external jugular vein and other veins. The anatomy of SMG is a complicated structure. Determining the main blood vessels of the submandibular gland is very important to achieve a successful vascularized autologous SMG transplant.


Virus-associated immunopathology: animal models and implications for human disease. 2. Cell-mediated immunity, autoimmune diseases, genetics, and implications for clinical research.
Part 2 of this memorandum describes further mechanisms whereby the interaction of a virus with the host's immune system may lead to tissue damage. Cell-mediated immunity plays a vital role in promoting recovery from virus infections, but under some circumstances tissue damage may be caused by the reaction of immune cells with viral antigens. When mice are infected with lymphocytic choriomeningitis virus neonatally or as adults while receiving immunosuppressive drugs, widespread invasion of cells is seen but there is little overt disease. If, however, normal adults are infected or if immune cells are transfused into tolerant mice, cell injury and death follow. Viruses have long been suspected of contributing to the pathogenesis of autoimmune diseases. Antibodies directed against normal cell constituents have been reported in several virus infections. Viruses may conceivably unmask or release host antigens, alter host antigens and act as "helper determinants", or perhaps in other ways provoke immune responses against normal body constituents. The immunopathological manifestations caused by viruses may also be influenced by the host's genetic makeup. Certain observations indicate that, in addition to controlling susceptibility to virus infection, genetic factors partly determine the effectiveness of the immune response. The memorandum calls attention to the possible implications of these concepts and findings for clinical research. Some of the diseases of animals and man that serve as models for studies of virus-associated immunopathology are briefly described.


Racial/Ethnic differences in receipt of naloxone distributed by opioid overdose prevention programs in New York City.
We evaluated racial/ethnic differences in the receipt of naloxone distributed by opioid overdose prevention programs (OOPPs) in New York City (NYC). We used naloxone recipient racial/ethnic data collected by OOPPs from April 2018 to March 2019. We aggregated quarterly neighborhood-specific rates of naloxone receipt and other covariates to 42 NYC neighborhoods. We used a multilevel negative binomial regression model to assess the relationship between neighborhood-specific naloxone receipt rates and race/ethnicity. Race/ethnicity was stratified into four mutually exclusive groups: Latino, non-Latino Black, non-Latino White and non-Latino Other. We also conducted racial/ethnic-specific geospatial analyses to assess whether there was within-group geographic variation in naloxone receipt rates for each racial/ethnic group. Non-Latino Black residents had the highest median quarterly naloxone receipt rate of 41.8 per 100,000 residents, followed by Latino residents (22.0 per 100,000), non-Latino White (13.6 per 100,000) and non-Latino Other residents (13.3 per 100,000). In our multivariable analysis, compared with non-Latino White residents, non-Latino Black residents had a significantly higher receipt rate and non-Latino Other residents had a significantly lower receipt rate. In the geospatial analyses, both Latino and non-Latino Black residents had the most within-group geographic variation in naloxone receipt rates compared to non-Latino White and Other residents. This study found significant racial/ethnic differences in naloxone receipt from NYC OOPPs. We observed substantial variation in naloxone receipt for non-Latino Black and Latino residents across neighborhoods, indicating relatively poorer access in some neighborhoods and opportunities for new approaches to address geographic and structural barriers in these locations.


Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways.
Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular reporters that can readily be manipulated. Cellular assays comprise genetic, molecular, and cytological reporters. The assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.


Harmonizing the interests of free speech, obscenity, and child pornography in cyberspace: the new roles of parents, technology, and legislation for internet safety.
Inadvertent access to website addresses and spam e-mails continue to make pornography rampant on the Internet in schools, homes, and libraries. Collectively, parents, teachers, and members of the community must become more aware of the risks and consequences of open access to the Internet, and the distinction between censorship and Internet access filtering. Parental involvement is crucial for raising children with healthy Internet habits to access social and educational materials. Although generations have coped with different times and trials, technology is ushering in new trials. Parents and communities cannot ignore the present and future technology ingrained into the lives of children. This paper contends that parents armed with legislation and technological security devices for access to the Internet ought to strengthen the character of online Internet safety. The discussion is focused on the roles that parents, communities, technology, and laws should play in order to protect children from obscene and pornographic threats from cyberspace. It is argued that the roles of education and technology should outweigh the legislative interventions of governments. A critique of significant litigations and laws on obscenity and pornography is presented. The paper offers a variety of security tools and techniques for protecting children from Internet access to obscene and pornographic materials. The impacts of pornographic materials on the welfare of children, adolescents, women, and families are discussed.


Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads.
For autologous chondrocyte transplantation (ACT) chondrocytes are expanded in vitro. During expansion these cells may dedifferentiate. This change in phenotype is characterized by a raised expression of type I collagen and a decrease in type II collagen expression. Since high expression of type II collagen is of central importance for the properties of hyaline cartilage, we investigated if the growth factor bone morphogenetic protein-2 (BMP-2) may modulate the chondrogenic phenotype in monolayer cell cultures and in three-dimensional culture systems. Chondrocytes from articular knee cartilage of 11 individuals (average age: 39.8 years) with no history of joint disease were isolated and seeded either in monolayer cultures or embedded in alginate beads in presence or absence of human recombinant BMP-2 (hr-BMP-2). Then, cells were harvested and analysis of the chondrogenic phenotype was performed using quantitative RT-PCR, immunocytochemistry and ELISA. Addition of BMP-2 to chondrocytes expanded in two-dimensional (2D) cultures during the first subculture (P1) had no effect on mRNA amounts encoding type II collagen and interleukin-1beta (IL-1beta). In contrast, seeding chondrocytes in three-dimensional (3D) alginate cultures raised type II collagen expression significantly and addition of BMP-2 enhanced this effect. We conclude that chondrocytes during expansion for ACT may benefit from BMP-2 activation only when seeded in an appropriate 3D culture system.


Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B.
Studies have suggested that glutamine synthetase (GS) is a potential marker of hepatocellular carcinoma (HCC). We aimed to evaluate the expression of GS in non-malignant liver tissue and serum GS levels in HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), five kinds of extrahepatic diseases patients and healthy subjects. Immunohistochemistry (IHC) was used to assess GS expression in 260 liver tissue samples (from 120 HCC, 90 CHB stage 4, and 50 CHB stage 1-3 patients). Enzyme-linked immunosorbent assays of 325 samples (from 100 healthy donors, 33 CHB stage 1-3, 43 CHB stage 4, 111 HCC, and 45 extrahepatic diseases patients) were used to further analyze GS levels in serum. IHC studies showed the expression of GS in 70% of HCC patients, 46.7% of CHB stage 4 patients and 38% of CHB stage 1-3 patients. The χ(2) tests showed significant difference between HCC samples and non-tumor tissues (P = 0.001 for HCC vs. CHB stage 4, P = 0.000 for HCC vs. CHB). Consistent with this, serum GS levels are increased in HCC and CHB stage 1-4 patients. There are significant differences among all samples (P = 0.000 for all), except CHB stage 1-3 versus CHB stage 4 (P = 0.552). Based on multiple linear regressions, HCC, CHB stage 1-4 and AFP were significantly associated with serum GS levels. In addition, in HCC group, TNM and Child-Pugh were significantly associated with GS levels. Expression of GS is increased in HCC, LC, and CHB. It may be a new serum marker for liver disease.


Chinese and Australians showed difference in mental time travel in emotion and content but not specificity.
Mental time travel refers to the ability to recall episodic past and imagine future events. The present study aimed to investigate cultural differences in mental time travel between Chinese and Australian university students. A total of 231 students (108 Chinese and 123 Australians) participated in the study. Their mental time travel abilities were measured by the Sentence Completion for Events from the Past Test (SCEPT) and the Sentence Completion for Events in the Future Test (SCEFT). Results showed that there were no cultural differences in the number of specific events generated for the past or future. Significant differences between the Chinese and Australian participants were found mainly in the emotional valence and content of the events generated. Both Chinese and Australian participants generated more specific positive events compared to negative events when thinking about the future and Chinese participants were more positive about their past than Australian participants when recalling specific events. For content, Chinese participants recalled more events about their interpersonal relationships, while Australian participants imagined more about personal future achievements. These findings shed some lights on cultural differences in episodic past and future thinking.


Carbon, nitrogen, and phosphorus distribution in particle size-fractionated separated pig and cattle slurry.
Solid liquid separation of animal slurry is a method to reduce the excess nutrient loads from intensive livestock production. Five different separation technologies (sedimentation, centrifugation, pressurized filtration, polymer flocculation and drainage, and iron chloride addition + polymer flocculation and drainage) were applied to pig and cattle slurry in a laboratory study. Separation efficiencies of mass, dry matter (DM), N, and P were measured. Particle size fractionation of the solid fractions was performed by subjecting them to wet fractionation and C, organic N (N(org)), and P contents were subsequently measured. Chemical pretreatment with polymer before gravity drainage separated DM, total N, and P from raw pig and cattle slurry with the highest efficiencies. Sedimentation and centrifugation separated P from pig and cattle slurries with higher simple separation efficiencies (0.77 and 0.70, respectively) compared with pressurized filtration (0.15 and 0.37). Pressurized filtration transferred the lowest masses (14 and 18%) to the solid fractions. Solid fractions from pig slurry generally contained higher concentrations of P and C compared with cattle slurry solid fractions. The majority of C in solid fractions was present in particles > 25 microm, whereas N and P were present in larger proportions in particles < 25 microm. Chemical pretreatment increased the capture of smaller N(org)- and P-rich particles into larger particles between 25 and 1000 microm.


Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.
The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.


The significance of anti-sialyl-Tn antibodies in patients with colorectal and breast cancer.
The sera of 54 individuals with colorectal or breast cancer, and 50 healthy volunteers were assayed for the presence of anti-bovine submaxillary mucin antibodies using an enzyme linked immunoassay. The serum levels of these antibodies were found to be significantly lower in people with breast (p < 0.001) or colorectal cancer (p < 0.001) with respect to healthy individuals. Within the colorectal cancer group the presence of antibodies was significantly lower in those individuals with poorly differentiated tumors compared to other histological grades (p < 0.05), but did not correlate with the presence of local or distant metastases or anatomical location of the tumor (p > 0.05). No correlation was found with respect to the age of the patient and the level of anti-sialyl-Tn antibodies (p > 0.05). Competition analysis with the anti-sialyl-Tn monoclonal antibody 3C2 indicated that the activity against bovine submaxillary mucin was primarily due to specificity for the sialyl-Tn epitope of the glycoprotein. In contrast to findings with other tumor associated antigens, we could find no evidence of an increase in the level of antibodies against this epitope.


Rural versus urban commuting patients with stage III colon cancer: is there a difference in treatment and outcome?
To evaluate if there are differences in outcomes for patients with stage III colon cancer in those from urban vs. rural commuting areas. Data were evaluated on patients diagnosed with stage III colon cancer between 2012 and2018 from the Louisiana Tumor Registry. Patients were classified into rural and urban groups. Data on overall survival, time from diagnosis to surgery and time from surgery to chemotherapy, and sociodemographic factors (including race, age, and poverty level) were recorded. Of 2652 patients identified, 2159 were urban (81.4%) and 493 rural (18.6%). No age difference between rural and urban patients (p = 0.56). Stage IIIB accounted for 66.7%, followed by IIIC (21.6%) and IIIA (11%), with a significant difference between rural and urban patients based on stage (p = 0.02). There was no difference in the extent of surgery (p = 0.34) or tumor size (p = 0.72) between urban and rural settings. No difference in undergoing chemotherapy (p = 0.12). There was a statistically significant difference in receiving timely treatment for hospital volume (p < 0.0001) and poverty level (p < 0.0001), but no difference in time from diagnosis to surgery (p = 0.48), and time from surgery to chemotherapy (p = 0.27). Non-Hispanic Blacks were less likely to receive timely treatment when compared with non-Hispanic Whites for both surgery and adjuvant chemotherapy, (aHR 0.91, 95% CI 0.83-0.99) and (aHR 0.86, 95% CI 0.77-0.97), respectively. There was no difference in Kaplan-Meier overall survival curves comparing rural vs. urban patients (p = 0.77). There was no statistical difference in overall survival, time to surgery, and time to adjuvant chemotherapy between rural and urban patients with Stage III colon cancer.


Heterosubtype neutralizing responses to influenza A (H5N1) viruses are mediated by antibodies to virus haemagglutinin.
It is increasingly clear that influenza A infection induces cross-subtype neutralizing antibodies that may potentially confer protection against zoonotic infections. It is unclear whether this is mediated by antibodies to the neuraminidase (NA) or haemagglutinin (HA). We use pseudoviral particles (H5pp) coated with H5 haemagglutinin but not N1 neuraminidase to address this question. In this study, we investigate whether cross-neutralizing antibodies in persons unexposed to H5N1 is reactive to the H5 haemagglutinin. We measured H5-neutralization antibody titers pre- and post-vaccination using the H5N1 micro-neutralization test (MN) and H5pp tests in subjects given seasonal vaccines and in selected sera from European elderly volunteers in a H5N1 vaccine trial who had detectable pre-vaccination H5N1 MN antibody titers. We found detectable (titer > or = 20) H5N1 neutralizing antibodies in a minority of pre-seasonal vaccine sera and evidence of a serological response to H5N1 in others after seasonal influenza vaccination. There was excellent correlation in the antibody titers between the H5N1 MN and H5pp tests. Similar correlations were found between MN and H5pp in the pre-vaccine sera from the cohort of H5N1 vaccine trial recipients. Heterosubtype neutralizing antibody to H5N1 in healthy volunteers unexposed to H5N1 is mediated by cross-reaction to the H5 haemagglutinin.


Capsular warning syndrome caused by middle cerebral artery stenosis.
The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.


Beneficial reuse of precast concrete industry sludge to produce alkaline stabilized biosolids.
The precast concrete industry generates waste called concrete sludge during routine mixer tank washing. It is highly alkaline and hazardous, and typically disposed of by landfilling. This study examined the stabilization of municipal sewage sludge using concrete sludge as an alkaline agent. Sewage sludge was amended with 10 to 40% of concrete sludge by wet weight, and 10 and 20% of lime by dry weight of the sludge mix. Mixes containing 30 and 40% of concrete sludge with 20% lime fulfilled the primary requirements of Category 1 and 2 (Canada) biosolids of maintaining a pH of 12 for at least 72 hours. The heavy metals were below Category 1 regulatory limits. The 40% concrete sludge mix was incubated at 52 degrees C for 12 of the 72 hours to achieve the Category 1 and 2 regulations of less than 1000 fecal coliform/g solids. The nutrient content of the biosolids was 8.2, 10 and 0.6 g/kg of nitrogen, phosphorus and potassium respectively. It can be used as a top soil or augmented with potassium for use as fertilizer. The study demonstrates that concrete sludge waste can be beneficially reused to produce biosolids, providing a long-term sustainable waste management solution for the concrete industry.


Multisource Longitudinal Network and Latent Variable Model Analyses of ADHD Symptoms in Children.
Objective: Multisource longitudinal network analysis was used to determine if between-child and within-child variance of attention-deficit/hyperactivity disorder (ADHD) symptoms provided unique findings of ADHD relative to latent variable model (LVM) analyses.Method: Mothers and fathers of 802 Spanish first-grade children (54% boys) provided ratings of ADHD symptoms at two time points six weeks apart (assessment 1: 723 mothers and 603 fathers; assessment 2: 667 mothers and 584 fathers). Network and latent variable models were applied to the ratings.Results: Inattention, hyperactivity, and mixed hyperactive/impulsive symptom communities occurred for the within- and between-children's symptom networks with the results being consistent across mothers and fathers, especially for the between-children's symptom networks. LVM analyses identified three factors with the same symptoms on each factor as in the symptom communities. These models also showed invariance across mothers and fathers as well as assessments.Conclusions: Longitudinal networks provided several useful insights for ADHD, including centrality symptoms that differed across between- and within-child levels. However, many findings were also largely consistent with the LVM analyses. Future studies should use novel methods (e.g., intensive longitudinal measurement) and analytic tools to determine if more unique theoretical and clinical findings emerge when applying network analysis to longitudinally measured ADHD symptoms.


Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.
The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients.


Impact of a brief intervention on cervical health literacy: A waitlist control study with jailed women.
Jailed women are four-five times more likely to have had cervical cancer compared to women without criminal justice histories. Previous research has shown that an important contributor to cervical cancer risk, and perhaps lack of follow-up, is incarcerated women's low health literacy about broader reproductive health issues. Little work has been done to address this disparity. Thus, the objective of this study was to test the effectiveness of an intervention to improve incarcerated women's cervical health literacy and ultimately address cervical cancer disparities. Using a waitlist control design, we compared changes in cervical health literacy (knowledge, beliefs, self-efficacy, and confidence for screening and follow-up) among 188 incarcerated women who completed a 10-hour intervention between 2014 and 2016 in three Kansas City jails. We used bivariate tests and multivariate analyses that controlled for baseline cervical health literacy level and key covariates. Women in the intervention group showed significant gains in seven out of eight cervical health literacy domains (all p < 0.01), whereas the control group only improved in one domain (p < 0.01). When controlling for covariates, the intervention group had less barriers, perceptions of seriousness, susceptibility to disease, and increased self-efficacy for cervical health screening and follow-up, compared to the control group (all p < 0.05). A brief intervention is an effective way to improve jailed women's cervical health literacy, but should be provided alongside systemic efforts that expand access to correctional preventive health services, including the human papillomavirus vaccine, community-based cancer screenings, and health insurance after women leave jails and transition back to communities.


Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase 1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin Resistance of Lung Cancer Cells.
Aldo-keto reductase 1B10 (AKR1B10) is overexpressed in several extraintestinal cancers, particularly in non-small-cell lung cancer, where AKR1B10 is a potential diagnostic marker and therapeutic target. Selective AKR1B10 inhibitors are required because compounds should not inhibit the highly related aldose reductase that is involved in monosaccharide and prostaglandin metabolism. Currently, 7-hydroxy-2-(4-methoxyphenylimino)-2H-chromene-3-carboxylic acid benzylamide (HMPC) is known to be the most potent competitive inhibitor of AKR1B10, but it is nonselective. In this study, derivatives of HMPC were synthesized by removing the 4-methoxyphenylimino moiety and replacing the benzylamide with phenylpropylamide. Among them, 4c and 4e showed higher AKR1B10 inhibitory potency (IC50 4.2 and 3.5 nM, respectively) and selectivity than HMPC. The treatments with the two compounds significantly suppressed not only migration, proliferation, and metastasis of lung cancer A549 cells but also metastatic and invasive potentials of cisplatin-resistant A549 cells.


Wireless inertial measurement unit (IMU)-based posturography.
Classical posturography techniques have been recently enhanced by the use of different motion tracking devices, but for technical reasons they are not used to track directly the body spatial position of a subject. To describe and clinically evaluate a wireless inertial measurement unit-based mobile system to track body position changes. The developed system used a calculus transformation method using the acceleration data corrected by Kalman and Butterworth filters to output position data. A prospective non-randomized clinical study involving 15 healthy subjects was performed to evaluate the agreement between the confidence ellipse areas synchronously measured by the new developed system and a classical posturography system while performing a modified clinical test of sensory interaction in balance. The overall intra-class correlation index was 0.93 (CI 0.89, 0.96). Grouped by conditions, under conditions 1-4, Pearson's correlation was 0.604, 0.78, 0.882, and 0.81, respectively. The developed wireless inertial measurement unit-based posturography system was valid for tracking the sway variances in normal subjects under habitual clinical testing conditions. Further studies are needed to validate this system on patients and also under other posture conditions.


Regulation of protease-activated receptor-2 expression in gingival fibroblasts and Jurkat T cells by Porphyromonas gingivalis.
Periodontal disease destroys the tooth-supporting tissues as a result of chronic inflammation elicited by bacterial accumulation on tooth surfaces. Porphyromonas gingivalis is a major periodontal pathogen, with a significant capacity to perturb connective tissue homeostasis and immune responses in the periodontium, attributed to its virulence factors, including a group of secreted cysteine proteases (gingipains). PAR-2 (protease-activated receptor-2) is a G-protein-coupled receptor activated upon proteolytic cleavage, mediating intracellular signalling events related to infection and inflammation, such as cytokine production. GF (gingival fibroblasts) and T cells have central roles in periodontal inflammation, which can potentially be mediated by PAR-2. The aims of this study were to investigate the effects of P. gingivalis on PAR-2 gene expression in human GF and Jurkat T cells, using quantitative real-time PCR, and to evaluate the involvement of gingipains. After 6 h of challenge with ascending concentrations of P. gingivalis, PAR-2 expression was up-regulated in both cell types by approximately 5-fold, compared with the control. The P. gingivalis concentration required for maximal PAR-2 induction was 4-fold greater in GF than Jurkat T cells. Heat inactivation or chemical inhibition of cysteine proteases abolished the capacity of P. gingivalis to induce PAR-2 expression in Jurkat T cells. In conclusion, P. gingivalis can induce PAR-2 expression in GF and Jurkat T cells, potentially attributed to its gingipains. These findings denote that P. gingivalis may perturb the host immune and inflammatory responses by enhancing PAR-2 expression, thus contributing to the pathogenesis of periodontal disease.


Women's experience of traumatic stress in cancer treatment.
In this study we investigated gender differences in the prevalence and predictors of posttraumatic stress disorder (PTSD) in a sample of cancer patients. Eighty-seven patients (59 women and 28 men) recruited from a local cancer clinic completed measures of individual coping style, social support resources, symptoms of PTSD, and the nature of the trauma associated with these symptoms. PTSD symptoms were more frequently reported by women (27% versus 10%). Predictors of PTSD for women were (1) perceived intensity of cancer treatment; (2) problems with health care professionals; (3) and cognitive avoidant coping style. For men, the sole predictor of elevated PTSD scores was behavioral avoidance. Women reported significantly higher levels of treatment intensity (TI), greater numbers and types of treatment, and more problems with health care professionals. Interpersonal and relational aspects of their illness were reported as most stressful, compared with men who were more concerned with work and finances. These differences may, in part, reflect an androcentric model of cancer treatment, which women experience as particularly stressful.


Monocytosis in the BXSB model for systemic lupus erythematosus.
Autoimmunity in BXSB mice is associated with a progressive increase in the number of peripheral blood mononuclear cells (PBMC). This is due to a marked rise in circulating monocytes, identified by: (a) their appearance on light and electron microscopy; (b) their surface antigenic characteristics; (c) their expression of Fc receptors; and (d) their capacity for phagocytosis. Among murine models for systemic lupus erythematosus, only the BXSB strain is characterized by monocytosis, suggesting that cells of monocytic lineage may contribute significantly to the pathogenesis of autoimmune disease in BXSB mice.


Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.
A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.


Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy.
Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM). Ktrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI). In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.


[Atraumatic diagnosis and semi-invasive therapy of subclavian steal syndrome using percutaneous transluminal angioplasty. A current concept].
Percutaneous transluminal angioplasty (PTA) is a semiinvasive, non-operative transvascular technique for dilatation of stenosed vessel segments by help of balloon catheters. This technique was applied to 30 out of 42 patients with a subclavian steal mechanism due to highgrade proximal subclavian artery (PSA) lesions. The transfemoral, transaxillary or both approaches were used. A staging of the severity of the subclavian steal mechanism on the basis of the pre-interventional Doppler ultrasound findings (Grade I-IV) was proposed for adequate selection of patients for angioplasty. During balloon dilatation of the subclavian artery permanent CW Doppler monitoring of the ipsilateral vertebral blood flow velocity was performed at the mastoid. Balloon dilatation failed to be effective in 4 patients with complete subclavian artery occlusions (Stage IV). In 26 patients with high-grade stenoses of the proximal subclavian artery (Stage II/III), angioplasty led to recanalisation of the vessel and abolishment of the steal mechanism. However, relief or improvement of the concomitant subclavian steal syndrome could not be achieved except in one-third or two-thirds of the patients, respectively. Long term follow-up with repeat Doppler sonography indicated a complete removal of the subclavian lesions in 50% of the cases, whereas the remaining patients produced some kind of re-stenosis. However, repeat angioplasty became necessary in only 5 cases and was permanently successful in two of them. If patients with complete subclavian artery occlusions were excluded, the complication rate due to angioplasty was very low. Embolism into the finger arteries could only be observed once. In another case, accidental dissection and complete occlusion of the distal subclavia artery occurred but underwent spontaneous recanalisation. Doppler monitoring of vertebral flow velocity was very useful for both control of the effectiveness of the dilatation procedure and deeper insight into the pathophysiology of the subclavian steal mechanism. An unexpected delay phenomenon concerning the re-establishment of cephalad vertebral flow direction was observed immediately after recanalisation of the subclavian artery and was thought to protect the posterior circulation against early embolism due to mobilisation of plaque debris within the proximal subclavian segment. From an angiological point of view, the outcome of percutaneous transluminal angioplasty does not yet meet the success rates of various modern extra-thoracic surgical procedures for operative treatment of subclavian steal mechanism. However, the rate of improvement of clinical signs and symptoms is equal with both methods.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte.
To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.


beta-N-acetylglucosaminidase in the reproductive organs and seminal plasma of the bull.
The highest specific activity of beta-N-acetylglucosaminidase (beta-NAG) was found in the different parts of the epididymis, where the activity seemed to be partly in secretory and partly in non-secretory, tissue-bound form. Epididymal spermatozoa also contained moderate beta-NAG activity. The beta-NAG was separated by chromatofocussing and anion exchange chromatography with HPLC into multiple forms with distinct pI values (8.0-4.0). The cauda epididymidis, ampulla and the seminal vesicles formed the major secretory sources of the high beta-NAG activity in bull seminal plasma. The major secretory forms of beta-NAG in caput and cauda epididymidis showed distinct elution profiles. In the fractionation with gel filtration on Sepharose 6B, the beta-NAG activities derived from bull testis and caput epididymidis had smaller molecular weights than did the secretory enzymes in seminal plasma, seminal vesicle secretion and cauda epididymidis. Maximum activity of all beta-NAG isoenzymes was observed at pH 5.0. They were almost totally inactivated at 60 degrees C and about 75-80% of the activity was lost at 55 degrees C. All the isoenzymes were strongly inhibited by thiol reagents but not with other metal ions and chelating agents. Histochemical studies showed a strong granular (lysosomal) reaction for beta-NAG in basal cells and basal parts of the principal cells in all but the initial segment of the epididymis. An apical (secretory) reaction was prominent in the distal caput and corpus as well as in distal cauda. After the distal caput the luminal sperm mass became increasingly mixed with a beta-NAG-positive material. The epithelial cells of the ampulla and seminal vesicle displayed a moderate apical (secretory) reaction.


Role of Advanced Imaging in the Diagnosis and Management of Active Legg-Calvé-Perthes Disease.
Since the first description of Legg-Calvé-Perthes disease a century ago, the diagnosis, staging, prognosis, and treatment decisions have been based on plain radiographs. The goal of treatment is prevention of femoral head deformity, yet radiographic prognostic classifications are applied in the fragmentation stage, often after deformity occurs. These classifications are assigned too late in the progression of the disease to maximize the effects of intervention. Thus, alternative mechanisms to determine femoral head involvement earlier in the disease course are warranted. Increasingly, MRI has been used in the study of the disease. Gadolinium-enhanced and diffusion-weighted MRI has shown promising results that correlate with radiographic classifications and the early radiographic outcome. Advanced imaging has improved the assessment of hinge abduction, yet the exact definition remains controversial. The role of imaging in the management of Legg-Calvé-Perthes disease is rapidly evolving. New or refined imaging techniques may eventually allow earlier prognosis and treatment.


Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years' follow-up.
Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients' treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0-8.2, p < 0.001, lymph node metastases: HR 3.5; 95 % CI 1.3-9.7, p = 0.02). When a shift in subtype inherence between primary tumour and metastatic lymph node was identified, the prognosis seemed to follow the subtype of the lymph node. Molecular profiles are not stable throughout tumour progression in breast cancer. Prognostic information for individual patients appears to be available from the analysis of biomarker expression in synchronous metastatic lymph nodes. The study supports biomarker analysis also in asynchronous relapses.


Insulin-like growth factor-binding protein-5 inhibits osteoblast differentiation and skeletal growth by blocking insulin-like growth factor actions.
Signaling through the IGF-I receptor by locally synthesized IGF-I or IGF-II is critical for normal skeletal development and for bone remodeling and repair throughout the lifespan. In most tissues, IGF actions are modulated by IGF-binding proteins (IGFBPs). IGFBP-5 is the most abundant IGFBP in bone, and previous studies have suggested that it may either enhance or inhibit osteoblast differentiation in culture and may facilitate or block bone growth in vivo. To resolve these contradictory observations and discern the mechanisms of action of IGFBP-5 in bone, we studied its effects in differentiating osteoblasts and in primary bone cultures. Purified wild-type (WT) mouse IGFBP-5 or a recombinant adenovirus expressing IGFBP-5WT each prevented osteogenic differentiation induced by the cytokine bone morphogenetic protein (BMP)-2 at its earliest stages without interfering with BMP-mediated signaling, whereas an analog with reduced IGF binding (N domain mutant) was ineffective. When added at later phases of bone cell maturation, IGFBP-5WT but not IGFBP-5N blocked mineralization, prevented longitudinal growth of mouse metatarsal bones in short-term primary culture, and inhibited their endochondral ossification. Because an IGF-I variant (R3IGF-I) with diminished affinity for IGFBPs promoted full osteogenic differentiation in the presence of IGFBP-5WT, our results show that IGFBP-5 interferes with IGF action in osteoblasts and provides a framework for discerning mechanisms of collaboration between signal transduction pathways activated by BMPs and IGFs in bone.


Charge profiles, RBRVS data and pre-estimates: a lesson in fee setting.
The author describes a method of setting reimbursement levels that--especially when combined with a physician negotiation program--may be the most effective cost-control mechanism of any with its level of simplicity.


Improving medication safety in the Intensive Care by identifying relevant drug-drug interactions - Results of a multicenter Delphi study.
Drug-drug interactions (DDIs) may cause adverse outcomes in patients admitted to the Intensive Care Unit (ICU). Computerized decision support systems (CDSSs) may help prevent DDIs by timely showing relevant warning alerts, but knowledge on which DDIs are clinically relevant in the ICU setting is limited. Therefore, the purpose of this study was to identify DDIs relevant for the ICU. We conducted a modified Delphi procedure with a Dutch multidisciplinary expert panel consisting of intensivists and hospital pharmacists to assess the clinical relevance of DDIs for the ICU. The procedure consisted of two rounds, each included a questionnaire followed by a live consensus meeting. In total the clinical relevance of 148 DDIs was assessed, of which agreement regarding the relevance was reached for 139 DDIs (94%). Of these 139 DDIs, 53 (38%) were considered not clinically relevant for the ICU setting. A list of clinically relevant DDIs for the ICU setting was established on a national level. The clinical value of CDSSs for medication safety could be improved by focusing on the identified clinically relevant DDIs, thereby avoiding alert fatigue.


Degradation of RXRs influences sensitivity of rat osteosarcoma cells to the antiproliferative effects of calcitriol.
Several cell lines, including ROS17/2.8 rat osteosarcoma (ROS) cells, contain functional VDRs and RXRs but are resistant to the antiproliferative effects of calcitriol and retinoids. We explored the role of receptor degradation in this hormone resistance. Results of transactivation assays indicated that ROS cells contain insufficient amounts of RXR to activate a DR-1 reporter, and Western blot analyses of cell extracts showed that the degradation of RXR is accelerated and produces an aberrant 45-kDa RXR. We stably expressed functional fluorescent chimeras of VDR and RXR [green fluorescent protein (GFP)-VDR; yellow fluorescent protein (YFP)-RXR] to evaluate degradation mechanisms and the impact of excess receptor expression on antiproliferative effects. Microscopy showed a diminished expression of YFP-RXR in ROS cells compared with the expression in CV-1 cells. Treatment with inhibitors of proteasomal degradation (lactacystin and MG132) selectively enhanced GFP-VDR and YFP-RXR expression and also increased the endogenous levels of VDR and RXR. Expression of GFP-VDR had no effect on the sensitivity of ROS cells to calcitriol. Increases of RXR levels by YFP-RXR expression, drug treatments, or the combination of the two, however, restored the growth-inhibitory effects of calcitriol and 9-cis-RA and restored p21 induction by calcitriol. These studies revealed that an accelerated and aberrant RXR degradation could cause resistance to the antiproliferative effects of calcitriol and retinoids in ROS cells.


Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study.
Platelet glycoprotein IIb/IIa (GpIIb-IIIa), a membrane receptor for fibrinogen and von Willebrand factor, has been implicated in the pathogenesis of acute coronary syndromes but has not been previously investigated in relation to stroke in young adults. We used a population-based case-control design to examine the association of the GpIIIa polymorphism P1A2 with stroke in young women. Subjects were 65 cerebral infarction cases (18 patients with and 47 without an identified probable etiology) 15 to 44 years of age from the Baltimore-Washington region and 122 controls frequency matched by age from the same geographic area. A face-to-face interview for vascular disease risk factors and a blood sample for the P1A2 allele and serum cholesterol were obtained from each participant. Logistic regression was used to estimate the odds ratio for one or more P1A2 alleles after adjustment for other risk factors. Among cases and controls, the prevalence rates of one or more P1A2 alleles were 21% and 22% among blacks and 36% and 28% among whites, respectively. This genotype was significantly associated with hypertension only in black control subjects but otherwise not with any of the established vascular risk factors. The adjusted odds ratio for cerebral infarction of one or more P1A2 alleles was 1.1 (confidence interval [CI], 0.6 to 2.3) overall, 0.5 (CI, 0.1 to 7.1) among blacks, and 1.4 (CI, 0.5 to 3.7) among whites. For the cases with an identified probable etiology, the corresponding odds ratios were 3.0 (CI, 0.9 to 10.4) overall, 0.7 (CI, 0.1 to 7.1) among blacks, and 12.8 (CI, 1.2 to 135.0) among whites. No association was found between the P1A2 polymorphism of GpIIIa and young women with stroke. However, subgroup analyses showed that the P1A2 polymorphism of GpIIIa appeared to be associated with stroke risk among white women, particularly those with a clinically identified probable etiology for their stroke. Further work with an emphasis on stroke subtypes and with multiracial populations is warranted.


Cognitive continuum theory in interprofessional healthcare: A critical analysis.
Effective clinical decision making is among the most important skills required by healthcare practitioners. Making sound decisions while working collaboratively in interprofessional healthcare teams is essential for modern healthcare planning, successful interventions, and patient care. The cognitive continuum theory (CCT) is a model of human judgement and decision making aimed at orienting decision-making processes. CCT has the potential to improve both individual health practitioner, and interprofessional team understanding about, and communication of, clinical decision-making processes. Examination of the current application of CCT indicates that this theory could strengthen interprofessional team clinical decision making (CDM). However, further research is needed before extending the use of this theoretical framework to a wider range of interprofessional healthcare team processes. Implications for research, education, practice, and policy are addressed.


Fibre-induced feed sorting in King Quail (Coturnix chinensis): behavioural plasticity elicited by a physiological challenge.
We examined the effect of an abrupt change in diet fibre content on the feed intake, gastrointestinal morphology and utilisation of gastroliths by a small (ca. 40 g body mass) herbivorous bird, the King Quail (Coturnix chinensis). King Quail were acclimated for 14 days on a low-fibre (LF) pullet starter diet. Following acclimation, half the quail population was immediately switched to a 23% wood-shaving diluted high-fibre (HF) diet for a further 14 days. Contrary to expectations, we found no differences in feed intake, gut morphology or gastrolith mass between the LF- and HF-fed quail. However, when switched from the LF to HF diet, the quail commenced feed-sorting behaviours that permitted HF-fed animals to maintain body condition (mass, abdominal fat mass) without adjustments to intestinal organ sizes or gastrolith mass. Feed sorting was initiated only after exposure to the HF diet, which corresponded with an immediate reduction in food intake, suggesting that the sorting behaviour was cued by a physiological challenge associated with the HF diet. This challenge apparently induced preferential sorting behaviour and was possibly due to abrupt changes in the rate of food passage, impacting satiation or other internal cues.


A Comparative Evaluation of Remineralizing Potential of Three Commercially Available Remineralizing Agents: An In Vitro Study.
An in vitro study to evaluate and compare the remineralization potential of commercially available remineralizing agents containing silver diamine fluoride (SDF), casein sucrose phosphate (CSP), casein phospho peptide-amorphous calcium phosphate (CPP-ACP) using DIAGNOdent. Thirty freshly extracted premolars for orthodontic treatment were collected. Specimens were randomly divided into 3 groups of 10 each: group I: SDF, group II: CSP, group III: CPP-ACP. The samples were subjected to DIAGNOdent analysis for recording the baseline values. Specimens were placed in demineralizing solution incubated at 37°C for 72 hours. DIAGNOdent values were recorded after demineralization. Following this, remineralization procedure was carried out using 3 different remineralizing agents: group I samples with SDF, group II with CSP, and group III with CPP-ACP. The remineralization procedure was performed to group I once and repeated for 14 days for group II and group III and storage solution was changed every 24 hours. The samples were subjected to DIAGNOdent analysis after 72 hours, 7 days, and 14 days and values were recorded. The data were analysed using Statistical Package for the Social Sciences (SPSS) with analysis of variance (ANOVA) and post hoc test. Intragroup comparison of DIAGNOdent readings showed a highly significant difference between baseline, postdemineralization, and postremineralization values. Among intergroup comparison, SDF showed maximum remineralization values followed by CSP and CPP-ACP, respectively. Silver diamine fluoride, CSP, and CPP-ACP are proven to possess remineralization potential. A comparative evaluation of these three remineralizing agents will aid in identifying most potent and effective agent in treating initial caries lesions in an effective noninvasive and child-friendly manner. Vinod D, Gopalakrishnan A, Subramani SM, et al. A Comparative Evaluation of Remineralizing Potential of Three Commercially Available Remineralizing Agents: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(1):61-65.


Mineralogy of asbestos.
The term asbestos collectively refers to a group of naturally occurring fibrous minerals which have been exploited in numerous commercial and industrial settings and applications dating to antiquity. Its myriad uses as a "miracle mineral" owe to its remarkable properties of extreme resistance to thermal and chemical breakdown, tensile strength, and fibrous habit which allows it to be spun and woven into textiles. Abundant in nature, it has been mined considerably, and in all continents save Antarctica. The nomenclature concerning asbestos and its related species is complex, owing to the interest held therein by scientific disciplines such as geology, mineralogy and medicine, as well as legal and regulatory authorities. As fibrous silicates, asbestos minerals are broadly classified into the serpentine (chrysotile) and amphibole (crocidolite, amosite, tremolite, anthophyllite, actinolite) groups, both of which may also contain allied but nonfibrous forms of similar or even identical chemical composition, nonpathogenic to humans. Recently, fibrous amphiboles, not historically classified or regulated as asbestos (winchite, richterite), have been implicated in the causation of serious disease due to their profusion as natural contaminants of vermiculite, a commercially useful and nonfibrous silicate mineral. Although generally grouped, classified, and regulated collectively as asbestos, the serpentine and amphibole groups have different geologic occurrences and, more importantly, significant differences in crystalline structures and chemical compositions. These in turn impart differences in fiber structure and dimension, as well as biopersistence, leading to marked differences in relative potency for causing disease in humans for the group of minerals known as asbestos.


Crossover experiments applied to network formation reactions: improved strategies for counting elastically inactive molecular defects in PEG gels and hyperbranched polymers.
Molecular defects critically impact the properties of materials. Here we introduce a paradigm called "isotopic labeling disassembly spectrometry" (ILDaS) that facilitates unprecedented precise experimental correlations between elastically inactive network defects (dangling chains and primary loops) and network formation kinetics and precursor structure. ILDaS is inspired by classical crossover experiments, which are often used to interrogate whether a reaction mechanism proceeds via an inter- or intramolecular pathway. We show that if networks are designed from labeled bifunctional monomers that transfer their labels to multifunctional junctions upon network formation, then the extent of junction labeling correlates directly with the number of dangling chains and cyclic imperfections within the network. We demonstrate two complementary ILDaS approaches that enable defect measurements with short analysis times, low cost, and synthetic versatility applicable to a broad range of network materials including polydisperse polymer precursors. The results will spur new experimental and theoretical investigations into the interplay between polymer network structure and properties.


Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets.
Rates of distal and junctional adenocarcinomas are increasing in Western countries. Systematic review of epidemiological evidence linking obesity to esophageal adenocarcinoma (EA) was performed for studies published from 2005 to 2010. The current understanding of obesity's role in the etiology and potential dysplastic progression of Barrett's esophagus (BE) to EA is reviewed. Accumulating epidemiological studies provide evidence of obesity's role as a driving force behind the increasing rates of EA. The simplest construct is that obesity promotes reflux, causing chronic inflammation and BE, predisposing to adenocarcinoma. However, as obesity is positively associated with the prevalence of many cancers, other mechanisms are important. A link may exist between fat distribution patterns and the risk of BE and EA. Altered metabolic profiles in the metabolic syndrome (MetS) may be a key factor in cell cycle/genetic abnormalities that mark the progression of BE towards cancer. Research highlighting a unique role of MetS in the length of BE, and its association with systemic inflammation and insulin resistance is discussed, as well as adipokine receptor expression in both BE and esophageal epithelium, and how MetS and the systemic response impacts on key regulators of inflammation and tumorigenesis. CONCLUSIONS/IMPACT: Obesity is positively associated with EA. The systemic inflammatory state consequent on the altered metabolism of obese patients, and the associated impact of adipocytokines and pro-coagulant factors released by adipocytes in central fat, may underlie obesity's relationship to this cancer. Novel therapeutic agents that may antagonize adipo-cytokines and potentially offer a promising role in cancer therapy are discussed.


Structural basis for the root effect in haemoglobin.
The remarkable ability of root effect haemoglobins to pump oxygen against high O2 gradients results from extreme, acid-induced reductions in O2 affinity and cooperativity. The long-sought mechanism for the root effect, revealed by the 2 angstrom crystal structure of the ligand-bound haemoglobin from Leiostomus xanthurus at pH 7.5, unexpectedly involves modulation of the R-state. Key residues strategically assemble positive-charge clusters across the allosteric beta1 beta2-interface in the R-state. At low pH, protonation of the beta N terminus and His 147(HC3)beta within these clusters is postulated to destabilize the R-state and promote the acid-triggered, allosteric R-->T switch with concomitant O2 release. Surprisingly, a set of residues specific to root effect haemoglobins recruit additional residues, conserved among most haemoglobins, to produce the root effect.


Update on long QT syndrome.
Long QT syndrome (LQTS) is an inherited disorder characterized by a prolonged QT interval in the 12-lead electrocardiogram and increased risk of malignant arrhythmias in patients with a structurally normal heart. Since its first description in the 1950s, advances in molecular genetics have greatly improved our understanding of the cause and mechanisms of this disease. Sixteen genes linked to LQTS have been described and genetic testing had become an integral part of the diagnosis and risk stratification. This article provides an updated review of the genetic basis, diagnosis, and clinical management of LQTS.