Interleukin-6 affects scopolamine-induced amnesia, but not brain amino acid levels in mice.
We have previously shown that, after peripheral administration, different cytokines affect cognitive functions in mice. In this study, we evaluated the effects of mouse interleukin-6 (IL-6) on the classical behavioural test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pretraining i.p. administration of this cytokine (0.125 and 0.5 microgram/mouse) significantly reduced the amnesic action of the muscarinic receptor antagonist. As it is well known that brain amino acids are deeply involved in the modulation of cognitive processes we measured the levels of glutamine, aspartic acid, glutamic acid and GABA in the hippocampus and hypothalamus of mice treated with IL-6. At both doses which affected the cognitive functions, this cytokine had no effect on brain levels of measured amino acids. Neither nociceptive thresholds to a thermal stimulus, nor spontaneous locomotor activity were modified by the acute administration of IL-6 (0.5 microgram/mouse). Our data confirm previous observations indicating that peripheral administration of cytokines affects some, but not other brain functions and suggest the involvement of IL-6 in the central modifications induced by the immune activation.


Type II DNA topoisomerases: enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break.
The T4 DNA topoisomerase is a recently discovered multisubunit protein that appears to have an essential role in the initiation of T4 bacteriophage DND replication. Treatment of double-stranded circular DNA with large amounts of this topoisomerase in the absence of ATP yields new DNA species which are knotted topological isomers of the double-stranded DNA circle. These knotted DNA circles, whether covalently closed or nicked, are converted to unknotted circles by treatment with trace amounts of the T4 topoisomerase in the presence of ATP. Very similar ATP-dependent enzyme activities capable of unknotting DNA are present in extracts of Drosophila eggs. Xenopus laevis eggs and mammalian tissue culture cells. The procaryotic enzyme, DNA gyrase, is also capable of unknotting DNA. We propose that these unknotting enzymes constitute a new general class of DNA topoisomerases (type II DNA topoisomerases). These enzymes must act via mechanisms that involve the concerted cleavage and rejoining of two opposite DNA strands, such that the DNA double helix is transiently broken. The passage of a second double-stranded DNA segment through this reversible double-strand break results in a variety of DNA topoisomerization reactions, including relaxation:super-coiling; knotting:unknotting and catenation:decatenation. In support of this type of mechanism, we demonstrate that the T4 DNA topoisomerase changes the linking number of a covalently closed double-stranded circular DNA molecule only by multiples of two. We discuss the possible roles of such enzymes in a variety of biological functions, along with their probable molecular mechanisms.


RECQ helicase RECQL4 participates in non-homologous end joining and interacts with the Ku complex.
RECQL4, a member of the RecQ helicase family, is a multifunctional participant in DNA metabolism. RECQL4 protein participates in several functions both in the nucleus and in the cytoplasm of the cell, and mutations in human RECQL4 are associated with three genetic disorders: Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. We previously reported that RECQL4 is recruited to laser-induced DNA double-strand breaks (DSB). Here, we have characterized the functional roles of RECQL4 in the non-homologous end joining (NHEJ) pathway of DSB repair. In an in vitro NHEJ assay that depends on the activity of DNA-dependent protein kinase (DNA-PK), extracts from RECQL4 knockdown cells display reduced end-joining activity on DNA substrates with cohesive and non-cohesive ends. Depletion of RECQL4 also reduced the end joining activity on a GFP reporter plasmid in vivo. Knockdown of RECQL4 increased the sensitivity of cells to γ-irradiation and resulted in accumulation of 53BP1 foci after irradiation, indicating defects in the processing of DSB. We find that RECQL4 interacts with the Ku70/Ku80 heterodimer, part of the DNA-PK complex, via its N-terminal domain. Further, RECQL4 stimulates higher order DNA binding of Ku70/Ku80 to a blunt end DNA substrate. Taken together, these results implicate that RECQL4 participates in the NHEJ pathway of DSB repair via a functional interaction with the Ku70/Ku80 complex. This is the first study to provide both in vitro and in vivo evidence for a role of a RecQ helicase in NHEJ.


Bilateral hearing loss during vincristine therapy: a case report.
Vincristine sulfate is a chemotherapeutic agent used in different cancer therapies. It is also the first choice of treatment for peripheral T-cell lymphoma with cyclophosphamide and adriamycin. Sudden hearing loss during vincristine therapy is a very rare event. This is a case of a 16-year old girl who developed sudden bilateral hearing loss related to vincristine therapy.


Fungal community composition in soils subjected to long-term chemical fertilization is most influenced by the type of organic matter.
Organic matter application is a widely used practice to increase soil carbon content and maintain soil fertility. However, little is known about the effect of different types of organic matter, or the input of exogenous species from these materials, on soil fungal communities. In this study, fungal community composition was characterized from soils amended with three types of organic matter over a 30-year fertilization experiment. Chemical fertilization significantly changed soil fungal community composition and structure, which was exacerbated by the addition of organic matter, with the direction of change influenced by the type of organic matter used. The addition of organic matter significantly increased soil fungal richness, with the greatest richness achieved in soils amended with pig manure. Importantly, following addition of cow and pig manure, fungal taxa associated with these materials could be found in the soil, suggesting that these exogenous species can augment soil fungal composition. Moreover, the addition of organic matter decreased the relative abundance of potential pathogenic fungi. Overall, these results indicate that organic matter addition influences the composition and structure of soil fungal communities in predictable ways.


Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study.
To compare intracranial pressure (ICP) in subjects with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG; subset of POAG), and ocular hypertension (OHT) with that in subjects with no glaucoma. The study was a retrospective review of medical records of 62,468 subjects who had lumbar puncture between 1985 and 2007 at the Mayo Clinic. Of these, 57 POAG subjects, 11 NTG subjects (subset of POAG), 27 OHT subjects, and 105 control subjects met the criteria and were analyzed. A masked comparison of the relationship between ICP and other ocular and nonocular variables was performed by using univariate and multivariate analyses. ICP was significantly lower in POAG compared with age-matched control subjects with no glaucoma (9.1 +/- 0.77 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.0001). Subjects with NTG also had reduced ICP compared with the control subjects (8.7 +/- 1.16 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.01). ICP was higher in OHT than in age-matched control subjects (12.6 +/- 0.85 mm Hg vs. 10.6 +/- 0.81 mm Hg; P < 0.05). ICP is lower in POAG and NTG and elevated in OHT. ICP may play an important role in the development of POAG and NTG and in preventing the progression of OHT to POAG. Further prospective and experimental studies are warranted to determine whether ICP has a fundamental role in the pathogenesis of glaucoma.


Protective Effects of Anethum graveolens Seed's Oil Nanoemulsion Against Cadmium-Induced Oxidative Stress in Mice.
The cadmium (Cd) is a toxic heavy metal that induces oxidative stress in both humans and animals. The plant phenolic compounds are capable of alleviating the toxicity of heavy metals. The encapsulation of plant bioactive compounds using nanoemulsion technology could enhance their bioefficacy. In this study, the protective effects of Anethum graveolens seed's oil nanoemulsion (AGN) against cadmium-induced oxidative stress in mice were studied. The results showed that the major bioactive compounds of essential oil were carvone and limonene. The result of particle size analysis revealed the pseudo-spherical droplets with nanometer size (148.8 ± 9.48 nm), homogenous dispersion, and physical colloidal stability. The Cd intoxication in mice (5 mg/kg BW for 30 days) reduced the body weight gain; however, treatment of the mice with different concentration of AGN (0.125, 0.25, and 0.5 mg/L, 30 days) through drinking water improved the body weight loss, liver Cd deposition, lipid peroxidation, cellular antioxidant redox potential, and inflammation in the liver, kidney, and brain of the mice challenged by cadmium-induced oxidative stress. The results of the present study revealed that drinking the essential oil of Anethum graveolens nanoemulsion containing carvone and limonene could be a promising strategy to protect the tissues against cadmium-induced oxidative damage.


Tensor renormalization group study of hard-disk models on a triangular lattice.
High accuracy and performance of the tensor renormalization group (TRG) method have been demonstrated for the model of hard disks on a triangular lattice. We considered a sequence of models with disk diameter ranging from a to 2sqrt[3]a, where a is the lattice constant. Practically, these models are good for approximate description of thermodynamics properties of molecular layers on crystal surfaces. Theoretically, it is interesting to analyze if and how this sequence converges to the continuous model of hard disks. The dependencies of the density and heat capacity on the chemical potential were calculated with TRG and transfer-matrix (TM) methods. We benchmarked accuracy and performance of the TRG method comparing it with TM method and with exact result for the model with nearest-neighbor exclusions (1NN). The TRG method demonstrates good convergence and turns out to be superior over TM with regard to considered models. Critical values of chemical potential (μ_{c}) have been computed for all models. For the model with next-nearest-neighbor exclusions (2NN) the TRG and TM produce consistent results (μ_{c}=1.75587 and μ_{c}=1.75398 correspondingly) that are also close to earlier Monte Carlo estimation by Zhang and Deng. We found that 3NN and 5NN models shows the first-order phase transition, with close values of μ_{c} (μ_{c}=4.4488 for 3NN and 4.4<μ_{c}<4.5 for 5NN). The 4NN model demonstrates continuous yet rapid phase transition with 2.65<μ_{c}<2.7.


Survival Impact of Perioperative Red Blood Cell Transfusion During Pancreatectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Propensity Score Matching Analysis.
The aim of this study was to show the real impact of perioperative red blood cell transfusion (PBT) on prognosis in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma. Patients who underwent pancreatectomy between 2004 and 2018 were enrolled. Short- and long-term outcomes in patients who received PBT (PBT group) were compared with those who did not (non-PBT group). From a total of 197 patients, 55 (27.9%) received PBT, and 142 (72.1%) did not. The PBT group displayed a higher level of carbohydrate antigen 19-9 (P = 0.02), larger tumor size (P < 0.001), and a higher rate of lymph node metastasis (P = 0.02), and underwent more frequent pancreaticoduodenectomy (P < 0.001) and portal vein resection (P < 0.001). Before matching, recurrence-free survival (RFS) and overall survival (OS) in the PBT group were significantly worse than the non-PBT group (RFS: hazard ratio [HR], 1.73 [P = 0.002]; OS: HR, 2.06 [P < 0.001]). After matching, RFS and OS in the PBT group were not significantly different from the non-PBT group (RFS: HR, 1.44 [P = 0.15]; OS: HR, 1.53 [P = 0.11]). Our results show that PBT has no survival impact in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma.


A common haplotype of carnitine palmitoyltransferase 1b is associated with the metabolic syndrome.
The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria to provide substrates for β-oxidation. We performed an analysis including three coding SNP in the muscle isoform of the CPT1b gene (rs3213445, rs2269383 and rs470117) and one coding SNP in the CPT2 gene (rs1799821) to find associations with traits of the metabolic syndrome (MetS). Male participants (n 755) from the Metabolic Intervention Cohort Kiel were genotyped and phenotyped for features of the MetS. Participants underwent a glucose tolerance test and a postprandial assessment of metabolic variables after a standardised mixed meal. Carriers of the rare CPT1b 66V (rs3213445) allele had significantly higher γ-glutamyl transpeptidase (GGT), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) activities (P< 0·0001, P= 0·03 and P= 0·048, respectively) and a higher fatty liver index (FLI, P= 0·026). Fasting and postprandial TAG (P= 0·007 and P= 0·009, respectively) and fasting glucose (P= 0·012) were significantly higher in 66V-allele carriers. The insulin sensitivity index determined after a glucose load was lower in those subjects (P= 0·005). Total cholesterol (P= 0·051) and LDL-cholesterol (P= 0·062) tended to be higher in 66V-allele carriers when compared with I66I homozygotes. Homozygosity of the rare K531E allele presented with lower GGT and GOT activities (P= 0·011 and P= 0·027, respectively). E531E homozygotes tended to have lower GPT and FLI (P= 0·078 and P= 0·052, respectively). CPT2 V368I (rs1799821) genotypic groups did not differ in the investigated anthropometric and metabolic parameters. The present results confirm the association of CPT1b coding polymorphisms with the MetS, with a deleterious effect of the CPT1b I66V and a protective impact of the CPT1b K531E SNP, whereas haplotype analysis indicates a relevance of the E531K polymorphism only.


Hydraulics of a sewer flushing gate.
This paper presents field experiments carried out in a 1.8 m height egg-shaped sewer in Lyon, France in order to contribute to the knowledge and the simulation of Hydrass flushing gates. The main results are: i) definition of an empirical relationship giving the flow discharged by the gate as a function of the upstream water level and its use in modelling the gate behaviour, and ii) observation of the flush propagation along the sewer and evaluation of the potential cleansing efficiency.


Pulmonary lobar hypertrophy in a foal.
Pulmonary lobar hypertrophy was diagnosed in a 4-hour-old Quarter Horse full-term foal that had respiratory arrest shortly after birth. The gross and microscopic appearances were consistent with polyalveolar lobe, a congenital anomaly of human infants.


Physiological evidence that light-mediated decrease in cyclic GMP is an intermediary process in retinal rod transduction.
Brief, intracellularly injected pulses of cyclic GMP transiently depolarized toad retinal rod outer segments (ROS). The depolarization is antagonized by light, perhaps by the activation of phosphodiesterase (PDE), as shown in the biochemical studies of others. As measured by the antagonism of cyclic GMP pulses by light, PDE activity peaks after the peak of the receptor potential and has approximately the same recovery time as the membrane voltage after weak illumination, but recovers more slowly than the membrane potential after strong illumination, as sensitivity does in other preparations. A cyclic GMP pulse delivered just after the hyperpolarizing phase of the receptor potential tends to turn off the light response. The kinetics of recovery from this turnoff are similar to those of the initial phase of the receptor potential. This similarity suggests that the initial phase of the receptor potential is controlled by light-activated PDE. Both EGTA and saturating doses of cyclic GMP block the light response, but only cyclic GMP increases response latency, which suggests that if calcium is involved in transduction, it is controlled by the hydrolysis of cyclic GMP. After brief pulses of cyclic AMP, a new steady state of increased depolarization occasionally develops. The effects described above also occur under these conditions. The results are consistent with the hypothesis that light-activated hydrolysis of cGMP is an intermediary process in transduction.


Medical and nursing students attitudes towards interprofessional education in Nepal.
In order to elicit the attitudes of final year medical and 3rd year undergraduate nursing students, towards interprofessional education (IPE), a survey using a 25-item questionnaire and a five-point Likert scale design was administered to a convenience sample of 60 students. In addition, two focus group discussions were carried out, one in each student group, using a topic guide. The findings suggest that the majority of the students were aware about the concept and importance of IPE. The learning reported by participants reflected two main issues: participants emphasized firstly the importance of communication skills, both with other professionals and with patients, and secondly the development of increased awareness of others' roles. Research has demonstrated the importance of learning together as well as learning from and about different professionals within the context of a shared learning experience. Respondents should undertake appropriate skills development in IPE and be provided with knowledge and experience to ensure that they are adequately equipped to work with or learn from one another.


[Light-induced amaurosis fugax].
Internal carotid artery atherosclerotic disease may present with a wide variety of ipsilateral ocular symptoms and signs that can herald a devastating stroke. Asymptomatic retinal emboli, transient monocular visual loss (also known as amaurosis fugax) and central retinal artery occlusion are the most common. A 66-year-old man presented several spells of monocular light-induced amaurosis fugax related to a severe carotid occlusive disease. Ancillary tests showed an exhausted cerebrovascular reactivity and visual evoked potentials demonstrated an increased latency. Following a carotid endarterectomy the patient remained asymptomatic and ancillary tests normalized. Our report supports the theory that light-induced amaurosis fugax occurs on a hemodynamic basis. A prompt recognition of this symptom is critical since symptomatic severe carotid stenosis implies a high risk of ipsilateral stroke.


Changes in socioeconomic inequalities in the use of dental care following major healthcare reform in Chile, 2004-2009.
The study examines changes in the distribution and socioeconomic inequalities of dental care utilization among adults after the major healthcare reform in Chile, 2004-2009. We evaluated the proportion of people who visited the dentist at least once in the previous two years, and the mean number of visits. These outcome variables were stratified by sex, age (20-39, 40-59, 60-63; ≥64 years), educational level (primary, secondary, higher), type of health insurance (public, private, uninsured), and socioeconomic status (quintiles of an asset-index). We also used the concentration index (CIndex) to assess the extent of socioeconomic inequalities in the use of dental care, stratified by age and sex as a proxy for dental care needs. The use of dental care significantly increased between 2004 and 2009, especially in those with public health insurance, with lower educational level and lower socioeconomic status. The CIndex for the total population significantly decreased both for the proportion who used dental care, and also the mean number of visits. Findings suggest that the use of dental care increased and socioeconomic-related inequalities in the utilization of dental care declined after a Major Health Reform, which included universal coverage for some dental cares in Chile. However, efforts to ameliorate these inequalities require an approach that moves beyond a sole focus on rectifying health coverage.


Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling.
Postoperative shivering and cold hypersensitivity are major side effects of acute and chronic opioid treatments respectively. TRPM8 is a cold and menthol-sensitive channel found in a subset of dorsal root ganglion (DRG) nociceptors. Deletion or inhibition of the TRPM8 channel was found to prevent the cold hyperalgesia induced by chronic administration of morphine. Here, we examined the mechanisms by which morphine was able to promote cold hypersensitivity in DRG neurons and transfected HEK cells. Mice daily injected with morphine for 5 days developed cold hyperalgesia. Treatment with morphine did not alter the expressions of cold sensitive TREK-1, TRAAK and TRPM8 in DRGs. However, TRPM8-expressing DRG neurons isolated from morphine-treated mice exhibited hyperexcitability. Sustained morphine treatment in vitro sensitized TRPM8 responsiveness to cold or menthol and reduced activation-evoked desensitization of the channel. Blocking phospholipase C (PLC) as well as protein kinase C beta (PKCβ), but not protein kinase A (PKA) or Rho-associated protein kinase (ROCK), restored channel desensitization. Identification of two PKC phosphorylation consensus sites, S1040 and S1041, in the TRPM8 and their site-directed mutation were able to prevent the MOR-induced reduction in TRPM8 desensitization. Our results show that activation of MOR by morphine 1) promotes hyperexcitability of TRPM8-expressing neurons and 2) induces a PKCβ-mediated reduction of TRPM8 desensitization. This MOR-PKCβ dependent modulation of TRPM8 may underlie the onset of cold hyperalgesia caused by repeated administration of morphine. Our findings point to TRPM8 channel and PKCβ as important targets for opioid-induced cold hypersensitivity.


Abnormal response of superior sinoatrial node to sympathetic stimulation is a characteristic finding in patients with atrial fibrillation and symptomatic bradycardia.
We hypothesized that unresponsiveness of superior sinoatrial node (SAN) to sympathetic stimulation is strongly associated with the development of symptomatic bradycardia in patients with atrial fibrillation (AF). We performed 3D endocardial mapping in healthy controls (group 1, n=10) and patients with AF without (group 2, n=57) or with (group 3, n=15) symptomatic bradycardia at baseline and during isoproterenol infusion. Corrected SAN recovery time was abnormal in 0%, 11%, and 36% of groups 1, 2, and 3, respectively (P=0.02). At baseline, 90%, 26%, and 7% (P<0.001) of the patients had multicentric SAN activation patterns. For groups 1, 2, and 3, the median distance from the superior vena cava-right atrial junction to the most cranial earliest activation site (EAS) was 5.0 (25-75 percentile range, 3.5-21.3), 10.0 (4-20), and 17.5 (12-34) mm at baseline (P=0.01), respectively, and 4.0 (0-5), 5.0 (1-10), and 15.0 (5.4-33.3) mm, respectively, during isoproterenol infusion (P=0.01), suggesting an upward shift of EAS during isoproterenol infusion. However, although the EAS during isoproterenol infusion was at the upper one third of the crista terminalis in 100% of group 1 and 78% of group 2 patients, only 20% of group 3 patients showed a move of the EAS to that region (P<0.001). Superior SAN serves as the EAS during sympathetic stimulation in patients without AF and in most patients with AF without symptomatic bradycardia. In contrast, unresponsiveness of superior SAN to sympathetic stimulation is a characteristic finding in patients with AF and symptomatic bradycardia.


An indole-based near-infrared fluorescent "Turn-On" probe for H2O2: Selective detection and ultrasensitive imaging of zebrafish gallbladder.
Fluorescent probes play essential roles in medical imaging, where the researchers can select one of many molecules to use to help monitor the status of living systems under investigation. To date, a few scaffolds that allow the in vivo detection of H2O2 are available only. Herein, we provide a highly sensitive and selective near-infrared fluorescent probe that detects H2O2 based on the ICT sensing mechanism. We report the first indole-incorporated fluorescent probe Indo-H2O2 that allows H2O2 detection with a LOD of 25.2 nM featuring a boronate group conjugated to an indole scaffold; the boronate cleaves upon reaction with H2O2. A 5-membered malononitrile derivative was incorporated; Indo-H2O2 has near-infrared (NIR) properties and the reaction time is low (∼25 min) compared to other related probes. Indo-H2O2 was successfully employed in both endogenous and exogenous imaging trials of H2O2 in living cells. Indo-H2O2 also allows the real-time monitoring of H2O2in vivo. It preferentially accesses the gallbladder of zebrafish. Our findings support Indo-H2O2 as a highly sensitive fluorescent NIR probe for detecting H2O2, and an idea to incorporate a central indole unit in future fluorescent probe designs.


Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway.
The induction of apoptosis of tumor cells by the colonic fermentation product butyrate is thought to be an important mechanism in protection against colorectal cancer. Because a major action of butyrate is to inhibit histone deacetylase (leading to chromatin relaxation and altered gene expression), butyrate may induce apoptosis by derepression of specific cell death genes. Here we show that butyrate and trichostatin A (a more selective inhibitor of histone deacetylase) induce the same program of apoptosis in Jurkat lymphoid and LIM 1215 colorectal cancer cell lines that is strictly dependent on new protein synthesis (within 10 h) and that leads to the conversion of the proenzyme form of caspase-3 to the catalytically active effector protease (within 16 h) and apoptotic death (within 24 h). Cells primed with a low concentration of butyrate that itself did not induce activation of caspase-3 or apoptosis were, nevertheless, rendered highly susceptible to induction of apoptosis by staurosporine (an agent that has recently been shown to act by causing mitochondrial release of cytochrome c). Synergy between butyrate and staurosporine was due to the presence of a factor in the cytosol of butyrate-primed cells which enhanced over 7-fold the activation of caspase-3 induced by the addition of cytochrome c and dATP to isolated cytosol. We propose that changes at the level of chromatin structure, induced by a physiological substance butyrate, lead to the expression of a protein that facilitates the pathway by which mitochondria activate caspase-3 and trigger apoptotic death of lymphoid and colorectal cancer cells.


Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa.
Linear growth delay (stunting) affects roughly 155 million children under the age of 5 years worldwide. Treatment has been limited by a lack of understanding of the underlying pathophysiological mechanisms. Stunting is most likely associated with changes in the microbial community of the small intestine, a compartment vital for digestion and nutrient absorption. Efforts to better understand the pathophysiology have been hampered by difficulty of access to small intestinal fluids. Here, we describe the microbial community found in the upper gastrointestinal tract of stunted children aged 2-5 y living in sub-Saharan Africa. We studied 46 duodenal and 57 gastric samples from stunted children, as well as 404 fecal samples from stunted and nonstunted children living in Bangui, Central African Republic, and in Antananarivo, Madagascar, using 16S Illumina Amplicon sequencing and semiquantitative culture methods. The vast majority of the stunted children showed small intestinal bacterial overgrowth dominated by bacteria that normally reside in the oropharyngeal cavity. There was an overrepresentation of oral bacteria in fecal samples of stunted children, opening the way for developing noninvasive diagnostic markers. In addition, Escherichia coli/Shigella sp. and Campylobacter sp. were found to be more prevalent in stunted children, while Clostridia, well-known butyrate producers, were reduced. Our data suggest that stunting is associated with a microbiome "decompartmentalization" of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.


Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice.
For studying rare hereditary Alzheimer's disease (AD), transgenic (Tg) animal models overexpressing amyloid-beta protein precursor (AbetaPP) followed by increased amyloid-beta (Abeta) formation are used. In contrast, sporadic AD has been proposed to start with an insulin-resistant brain state (IRBS).We investigated the effect of IRBS induced by intracerebroventricularly (icv) administered streptozotocin (STZ) on behavior, glycogen synthase kinase-3 (GSK) alpha/beta content, and the formation of AD-like morphological hallmarks Abeta and tau protein in AbetaPP Tg2576 mice. Nine-month-old Tg mice were investigated 6 months after a single icv injection of STZ or placebo. Spatial cognition was analyzed using the Morris water maze test. Soluble and aggregated Abeta40/42 fragments, total and phosphorylated tau protein, and GSK-3alpha/beta were determined by ELISA. Cerebral (immuno)histological analyses were performed. In Tg mice, STZ treatment increased mortality, reduced spatial cognition, and increased cerebral aggregated Abeta fragments, total tau protein, and congophilic amyloid deposits. These changes were associated with decreased GSK-3alpha/beta ratio (phosphorylated/total). A linear negative correlation was detected between Abeta42 and cognition, and between GSK-3alpha/beta ratio and aggregated Abeta40+42. No marked necrotic and apoptotic changes were observed. In conclusion, IRBS may aggravate AD-like changes such as behavioral and increase the formation of pathomorphological AD hallmarks via GSK-3alpha/beta pathway in AbetaPP-overexpressing mice.


Relative importance of cigarette smoking in occupational lung disease.
Since 1900 respiratory disease has remained a constant serious cause of chronic ill health and premature death in Britain. The falling importance of tuberculosis and pneumonia has been off-set by the rise in lung cancer. Bronchitis morbidity and mortality have fallen only slightly since 1935. To produce any real improvement in the future existing information as to cause must be studied. The relative contribution of occupational exposure is compared with the importance of cigarette smoking. Relevant information is scanty and has been produced to emphasise the existence of occupational diseases rather than assess their importance to the community as whole. In Britain the evidence is that within the coal mining and iron and steel industries conditions are now such that dust exposure contributes little to the morbidity or mortality compared with the workers' smoking habits. Similar results have been shown by a cross-sectional survey of many dusty occupations in Western Germany. Only in the disappearing Welsh slate industry has dust disease been at least as important as smoking. Until the current regulations were introduced conditions existed among asbestos workers such that the combined effect of cigarette smoking and dust exposure led to a loss of life expectation of over 10 years in moderate smokers. Since the new regulations were introduced the risk for asbestos workers should approximate to that for other industrial workers. While control of occupational exposure to respiratory hazards remains important, a far greater improvement to respiratory health would be produced by controlling tobacco smoking.


Enforced abstinence from tobacco during in-patient dual-diagnosis treatment improves substance abuse treatment outcomes in smokers.
Although the prevalence of tobacco use in those in substance abuse treatment is known to be quite high, most treatment programs do not address tobacco. The purpose of this study was to determine substance abuse recovery rates a year after treatment in a fully integrated, 90-day inpatient, dual diagnosis treatment program where patients are required to quit tobacco use in addition to drug and alcohol use for the duration of their 3 month stay. Tobacco is treated in the same way as other drugs and alcohol. One hundred fifty-four patients enrolled in a yearlong follow-up after treatment study consisting of monthly phone contact to assess recovery from substance abuse. One hundred forty (n=140) patients completed the year follow-up. At the time of entry into the program 120 (86%) were using tobacco daily. At the end of the year this decreased to 102 (73%). Patients who were using tobacco were more likely to relapse to other drugs or alcohol (p = .01). Patients who actively attempted to abstain from tobacco after treatment were significantly more likely to remain continuously abstinent throughout the year (p = .03). This study demonstrates that tobacco use is correlated with relapse and addressing tobacco in treatment as seriously as and in the same fashion as other drugs, improves outcomes. When provided with a tobacco free treatment environment for 90 days, patients with substance abuse and mental illness can and do make the decision to quit tobacco and stay quit, aiding their ability to remain sober.


Responses and molecular heterogeneity of IR-GIP after intraduodenal glucose and fat.
The plasma responses and molecular heterogeneity of human immunoreactive gastric inhibitory polypeptide (IR-GIP) after intraduodenal administration of equicaloric amounts of glucose (25 g) and fat (10 g) were determined with five different antisera. Two of these do not cross-react with 8 kdaltons (kDa) IR-GIP. In the fasting state plasma IR-GIP concentrations were highest measured with antisera, which detected both 5 and 8 kDa IR-GIP. The total integrated or incremental IR-GIP areas were similar after glucose and fat when determined with the same antiserum. When antisera with similar cross-reactivity with human 5 kDa IR-GIP were compared, no difference in incremental IR-GIP areas after either stimulus was found between antisera that did and did not measure 8 kDa IR-GIP. Gel filtration of plasma showed a consistent increase in 5 kDa IR-GIP 60 min after both glucose and fat but small and inconsistent changes in 8 kDa IR-GIP. Thus fat on a weight and molar basis is more potent than glucose in releasing IR-GIP. Both fat and glucose release predominantly the 5 kDa IR-GIP. Although of importance for the absolute IR-GIP level in plasma, 8 kDa IR-GIP contributes little to the increase in IR-GIP after both stimuli.


Broadband telecom photon pairs from a fiber-integrated PPLN ridge waveguide.
We demonstrate a spectrally correlated photon-pair source at telecom wavelengths (spanning across the S-, C-, and L-bands), based on type-0 spontaneous parametric downconversion (SPDC) in a fiber-coupled Zn-indiffused MgO doped periodically poled lithium niobate (PPLN) ridge waveguide. Modal analysis of the waveguide performed through numerical finite element method (FEM) simulation indicates that device temperature can be used to dramatically vary and control the emission spectrum. Efficient photon-pair generation is measured over a broad wavelength range from ∼1520 - 1580 nm [full width at half maximum (FWHM) > 45 nm] with a coincidence-to-accidental ratio (CAR) as high as ∼668 and spectral brightness ∼2.5 × 107 pairs/s/mW/nm. Such sources can be employed in wavelength division multiplexed (WDM) quantum key distribution (QKD) over existing fiber-optic networks.


The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23.
Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4(+) and CD8(+) T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs), which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S) 19, which has previously been employed successfully to vaccinate cattle. We first looked into the potential of S19 to hamper the cytokine-induced maturation of DCs; however, infected cells expressed CD25, CD40, CD80, and CD86 to a comparable extent as uninfected, cytokine-matured DCs. Furthermore, S19 activated DCs in the absence of exogeneous stimuli, enhanced the expression of HLA-ABC and HLA-DR, and was able to persist intracellularly without causing cytotoxicity. Thus, DCs provide a cellular niche for persisting brucellae in vivo as a permanent source of antigen. S19-infected DCs produced IL-12/23p40, IL-12p70, and IL-10, but not IL-23. While heat-killed bacteria also activated DCs, soluble mediators were not involved in S19-induced activation of human DCs. HEK 293 transfectants revealed cellular activation by S19 primarily through engagement of Toll-like receptor (TLR)2. Thus, as an immunological prerequisite for vaccine efficacy, B. abortus S19 potently infects and potently activates (most likely via TLR2) human DCs to produce Th1-promoting cytokines.


[Coronary artery aneurysm associated with fistula: two anatomically similar cases with different clinical presentation].
Coronary artery fistulas are rare anomalies and their association with a coronary aneurysm even more infrequent. We report two cases which are illustrative because of their different clinical presentations. In the first case the diagnosis was made after discovering fortuitously a heart murmur. In contrast in the second case the coronary artery fistula was demonstrated during a check-up for thoracic pain. In both cases the right coronary artery gave a fistulous communication to the right atrium.


Diffusion-weighted magnetic resonance and magnetization transfer imaging in the assessment of ischemic human stroke.
We compared characteristic features in ischemic stroke lesions from the hyperacute to the chronic stage on diffusion-weighted (DW) and magnetization transfer (MT) images with those on T2-weighted (T2W) images, and assessed changes in apparent diffusion coefficient (ADC), MT effect (MTe), and T2 ratios (infarct/normal) over time. DW images were particularly useful for detecting hyperacute infarcts within 6 hours of onset and in distinguishing acute lesions from chronic lesions. ADC ratios were lower within 7 days after onset and rose toward 1.0 in the subacute phase, becoming relatively isotense on ADC maps, but elevated thereafter. Although MTe ratios were unchanged or only subtly changed in the acute stage, they became significantly lower in the subacute and chronic stages. These combined magnetic resonance (MR) techniques were useful in the assessment of ischemic stroke and facilitated the determination of the age of cerebral infarct.


CONQUEST Quality Standards: For the Collaboration on Quality Improvement Initiative for Achieving Excellence in Standards of COPD Care.
Chronic obstructive pulmonary disease (COPD) are managed predominantly in primary care. However, key opportunities to optimize treatment are often not realized due to unrecognized disease and delayed implementation of appropriate interventions for both diagnosed and undiagnosed individuals. The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) is the first-of-its-kind, collaborative, interventional COPD registry. It comprises an integrated quality improvement program focusing on patients (diagnosed and undiagnosed) at a modifiable and higher risk of COPD exacerbations. The first step in CONQUEST was the development of quality standards (QS). The QS will be imbedded in routine primary and secondary care, and are designed to drive patient-centered, targeted, risk-based assessment and management optimization. Our aim is to provide an overview of the CONQUEST QS, including how they were developed, as well as the rationale for, and evidence to support, their inclusion in healthcare systems. The QS were developed (between November 2019 and December 2020) by the CONQUEST Global Steering Committee, including 11 internationally recognized experts with a specialty and research focus in COPD. The process included an extensive literature review, generation of QS draft wording, three iterative rounds of review, and consensus. Four QS were developed: 1) identification of COPD target population, 2) assessment of disease and quantification of future risk, 3) non-pharmacological and pharmacological intervention, and 4) appropriate follow-up. Each QS is followed by a rationale statement and a summary of current guidelines and research evidence relating to the standard and its components. The CONQUEST QS represent an important step in our aim to improve care for patients with COPD in primary and secondary care. They will help to transform the patient journey, by encouraging early intervention to identify, assess, optimally manage and followup COPD patients with modifiable high risk of future exacerbations.


Exploratory analysis of multiple omics datasets using the adjusted RV coefficient.
The integration of multiple high-dimensional data sets (omics data) has been a very active but challenging area of bioinformatics research in recent years. Various adaptations of non-standard multivariate statistical tools have been suggested that allow to analyze and visualize such data sets simultaneously. However, these methods typically can deal with two data sets only, whereas systems biology experiments often generate larger numbers of high-dimensional data sets. For this reason, we suggest an explorative analysis of similarity between data sets as an initial analysis steps. This analysis is based on the RV coefficient, a matrix correlation, that can be interpreted as a generalization of the squared correlation from two single variables to two sets of variables. It has been shown before however that the high-dimensionality of the data introduces substantial bias to the RV. We therefore introduce an alternative version, the adjusted RV, which is unbiased in the case of independent data sets. We can also show that in many situations, particularly for very high-dimensional data sets, the adjusted RV is a better estimator than previously RV versions in terms of the mean square error and the power of the independence test based on it. We demonstrate the usefulness of the adjusted RV by applying it to data set of 19 different multivariate data sets from a systems biology experiment. The pairwise RV values between the data sets define a similarity matrix that we can use as an input to a hierarchical clustering or a multidimensional scaling. We show that this reveals biological meaningful subgroups of data sets in our study.


Promoting Physical Activity With Self-Tracking and Mobile-Based Coaching for Cardiac Surgery Patients During the Discharge-Rehabilitation Gap: Protocol for a Randomized Controlled Trial.
Home-based cardiac rehabilitations (CRs) with digital technologies have been researched and implemented to replace, augment, and complement traditional center-based CR in recent years with considerable success. One problem that technology-enhanced home-based CR can potentially address is the gap between cardiac interventions and formal CR programs. In the Netherlands and some other countries (eg, Australia), patients after cardiac interventions stay at home for 3-4 weeks without much support from their physicians, and often engage in very little physical activity (PA). A home-based exercise program enabled by digital technologies may help patients to better prepare for the later center-based CR programs, potentially increasing the uptake rate of those programs. In a randomized controlled trial (RCT), we will evaluate the effectiveness of a home-based walking exercise program enhanced by self-tracking and mobile-based coaching (treatment condition), comparing it with a version of the same program without these technologies (control condition). The added value of the digital technologies is justified if patients in the treatment group walk more steps on average (primary outcome) and show better physical fitness in a bicycle ergometer test and higher self-efficacy toward PA (secondary outcomes). Based on a power analysis, we will recruit 100 cardiac patients and assign them evenly to the 2 parallel groups. Eligible patients are those who are scheduled in the postanesthesia care unit, know the Dutch language, have basic literacy of using smartphones, and are without medical conditions that may increase risks associated with PA. In a face-to-face meeting with a nurse practitioner, all patients are prescribed a 3-week exercise program at home (2 walking exercises per day with increasing duration), based on national and international guidelines and tailored to their physical conditions after cardiac intervention. Their physical activities (daily steps) will be measured by the Axivity AX3 accelerometer worn at hip position. Patients in the treatment group will also be supported by a Neo Health One self-tracking device and a mobile platform called Heart Angel, through which they are monitored and coached by their nurses. After the study, all patients will perform a bicycle ergometer test and return the devices within 1 week. In addition, 5 questionnaires will be sent to the patients by emails to assess their self-efficacy toward PA and other psychological states for exploratory analyses (at discharge, at the end of each monitoring week, and 1 week after the study). To minimize bias, the randomization procedure will be performed after introducing the exercise program, so the nurse practitioners are blind to the experimental conditions until that point. The study protocol has been approved by the Medical Research Ethics Committees United on February 26, 2018 (NL 62142.100.17/R17.51). By the end of 2018, we completed a small pilot study with 8 patients and the results based on interviews and app usage data suggest that a larger clinical trial with the targeted population is feasible. We expect to complete the RCT by the end of 2021, and statistical analyses will follow. Results of the RCT will help us to test the hypothesized benefits of self-tracking and mobile-based coaching for cardiac patients in home-based exercise programs during the discharge-rehabilitation gap. If the results are positive, cost-effectiveness analysis will be performed based on the insights of the study to inform the translation of the technology-enhanced program to clinical practice. We also note limitations of the trial in the discussion. Registered at Netherlands Trial Register NL8040; https://www.trialregister.nl/trial/8040. PRR1-10.2196/16737.


Modeling filtration of dispersed crude oil droplets by the copepod Calanus finmarchicus.
Oil droplets may form and disperse in the water column after an accidental spill of crude oil or petroleum products at sea. Micro-sized oil droplets may be available for filter feeding organisms, such as the copepod Calanus finmarchicus, which has been shown to filter oil droplets. In the present paper, a modeling approach was used to estimate potential ingestion amounts by copepod filtration of oil droplets. The new model was implemented in the OSCAR (Oil Spill Contingency and Response) software suite, and tested for a series of oil spill scenarios and key parameters. Among these, the size of the filtered droplets was found to be the most important factor influencing the model results. Given the assumptions and simplifications of the model, filtration of dispersed crude oil by C. finmarchicus was predicted to affect the fate of 1-40% of the total released oil mass, depending on the release scenario and parameter values used, with the lower end of that range being more probable in an actual spill situation.


Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension.
To review the literature on the use of hypertonic saline (HS) in treating cerebral edema and intracranial hypertension. Review of scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through November 1999. Pertinent literature is referenced, including clinical and laboratory investigations, to demonstrate principles and efficacy of treatment with HS in patients with intracranial space-occupying pathology. The literature was reviewed to summarize the mechanisms of action, efficacy, adverse effects, systemic effects, and comparisons with standard treatments in both clinical and laboratory settings. HS has an osmotic effect on the brain because of its high tonicity and ability to effectively remain outside the bloodbrain barrier. Numerous animal studies have suggested that fluid resuscitation with HS bolus after hemorrhagic shock prevents the intracranial pressure (ICP) increase that follows resuscitation with standard fluids. There may be a minimal benefit in restoring cerebral blood flow, which is thought to be mitigated through local effects of HS on cerebral microvasculature. In animal models with cerebral injury, the maximum benefit is observed in animals with focal injury associated with vasogenic edema (cryogenic injury). The ICP reduction is seen for < or =2 hrs and may be maintained for longer periods by using a continuous infusion of HS. The ICP reduction is thought to be caused by a reduction in water content in areas of the brain with intact blood-brain barrier such as the nonlesioned hemisphere and cerebellum. Most comparisons with mannitol suggest almost equal efficacy in reducing ICP, but there is a suggestion that mannitol may have a longer duration of action. Human studies published to date reporting on the use of HS in treating cerebral edema and elevated ICP include case reports, case series, and small controlled trials. Results from studies directly comparing HS with standard treatment in regard to safety and efficacy are inconclusive. However, the low frequency of side effects and a definite reduction of ICP observed with use of HS in these studies are very promising. Systemic effects include transient volume expansion, natriuresis, hemodilution, immunomodulation, and improved pulmonary gas exchange. Adverse effects include electrolyte abnormalities, cardiac failure, bleeding diathesis, and phlebitis. Although unproven, a potential for central pontine myelinolysis and rebound intracranial hypertension exists with uncontrolled administration. HS demonstrates a favorable effect on both systemic hemodynamics and intracranial pressure in both laboratory and clinical settings. Preliminary evidence supports the need for controlled clinical trials evaluating its use as resuscitative fluid in brain-injured patients with hemorrhagic shock, as therapy for intracranial hypertension resistant to standard therapy, as firstline therapy for intracranial hypertension in certain intracranial pathologies, as small volume fluid resuscitation during spinal shock, and as maintenance intravenous fluid in neurocritical care units.


Assessing the between-background stability of metabolic effects arising from lignin-related transgenic modifications, in two Populus hybrids using non-targeted metabolomics.
The advances in 'high-throughput' biology have significantly expanded our fundamental understanding of complex biological processes inherent to tree growth and development. Relative to the significant achievements attained with whole genome re-sequencing and transcriptomics efforts, the development and power of post-transcriptional tools such as proteomics and metabolomics continue to lag behind in tree biology. However, the inclusion of these powerful functional genomics platforms should substantially enable systems biology assessments of tree development, physiology and response(s) to biotic and abiotic stresses. Herein, we employ a non-targeted metabolomics platform to elucidate the metabolic plasticity of xylem lignification in distinct hybrid poplar genetic backgrounds, as well as in transgenic trees in these backgrounds expressing two common constructs: the first construct (C4H::F5H) augments monolignol content (syringyl:guaiacyl (S:G) ratio), while the second construct (C3'H-RNAi) reduces cell wall lignification. The results clearly show that genotype-specific metabolism exists, and provide an appropriate foundation for properly comparing the influence of background on the relationships between metabolic and specific phenotypic traits. Moreover, it was apparent that transgene-induced phenotypic gradients in cell wall chemical wood can be associated with global metabolism of secondary xylem biosynthesis, however in a genotype-specific manner. This result implies that the same may be true for phenotypic gradients arising through natural genetic variation, intensive breeding or environmental factors. It is also apparent that while distinct, at a global level the wood-forming metabolisms of different poplar hybrids can, to some extent, respond similarly to the influences of genetic manipulation of lignin-related genes. This further implies that with the correct approach, it may be possible to associate the emergence of specific wood traits from different genetic backgrounds-be they transgene-induced or otherwise-with stable metabolic signatures.


Genotypic and Phenotypic Characterization of Salmonella Isolated from Fresh Ground Meats Obtained from Retail Grocery Stores in the Brookings, South Dakota, Area.
Salmonella is one of the most common foodborne pathogens found in retail fresh meat products. The purpose of this study was to characterize the Salmonella that is found in common types of fresh ground meats available to consumers in grocery stores in the Brookings, South Dakota, area. Salmonella serotypes were detected in 50 (19%) of 261 retail fresh ground meat samples, with 2 (2%) of 115 ground turkey samples, 6 (14%) of 42 chicken samples, and 42 (40%) of 104 ground pork samples testing positive for Salmonella. The Salmonella isolates were sequenced using an Illumina MiSeq genome sequencer. The resulting genomic sequences were analyzed to determine the serotypes of the isolates and to detect the presence of virulence and antibiotic resistance genes. The Salmonella isolated from the ground meats belonged to 23 different serotypes. The predominant serotype isolated from ground chicken was Enteriditis (5 of 6, 83%). Among the ground pork isolates, the most common serotypes were the potential monophasic variant of Typhimurium (5 of 42, 12%), Uganda (5 of 42, 12%), Anatum (4 of 42, 10%), Derby (3 of 42, 7%), Infantis (3 of 42, 7%), and London (3 of 42, 7%). Among the 45 Salmonella isolates tested to determine their resistance to common veterinary antibiotics, 25 (56%) were found to be susceptible to all 14 antibiotics tested, 11 (24%) were resistant to 1 antibiotic, 4 (9%) were resistant to 2 antibiotics, 1 (2%) was resistant to 3 antibiotics, 2 (4%) were resistant to 4 antibiotics, 1 (2%) was resistant to 8 antibiotics, and 1 (2%) was resistant to 10 antibiotics. The most common antibiotic resistances observed in this study were to streptomycin (15 of 45, 33%), tetracycline (11 of 45, 24%), and sulfisoxazole (7 of 45, 16%). The results of phenotypic evaluation of antibiotic resistance profiles of Salmonella isolates correlated well with the antibiotic resistance genes detected in the genomic sequences of the isolates.


Increased expression of COX-2 in the development of human lung cancers.
It is well accepted that an increase in the expression of cyclooxygenase-2 (COX-2), a key inducible enzyme involved in the production of prostaglandins and other eicosanoids, may play a significant role in carcinogenesis in addition to its well-known role in inflammatory reactions. Whereas previous studies were largely confined to colorectal tumorigenesis, we have shown that a significantly increased expression of COX-2 may also play a role in the development of lung cancer. COX-2 expression was found to be frequently elevated in lung cancer, especially in adenocarcinoma, and the proportion of lung cancer cells with marked COX-2 expression was much higher in lymph node metastases than in the corresponding primary tumors. It was also shown that early stage adenocarcinoma patients with increased COX-2 expression who were surgically treated had a shorter survival. Our studies, which used high- and low-metastatic human lung cancer cell sublines established in our laboratory, revealed an association between metastatic capabilities and COX-2 expression levels: COX-2-specific inhibitors could inhibit in vitro the invasion of the highly metastatic NCI-H460-LNM35 clone through Matrigel-containing basement membrane components as well as the spontaneous in vivo metastasis in SCID mice. Taken together, these findings suggest that an increase in COX-2 expression maybe associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype.


Factors influencing physician use of clinical electronic information technologies after adoption by their medical group practices.
A major factor limiting efficiency and quality gains from clinical information technologies is the lack of full use by the clinicians. To identify the practice and physician characteristics that influence the use of e-scripts after adoption. Data were obtained from 27 primary care medical group practices that had e-script technology for 2 years. Physician and practice characteristics were obtained from the clinics, and the proportion of each physician's prescriptions sent electronically was calculated from the prescription records. Practice culture data were obtained from a survey of the physicians in each practice. Data were analyzed using hierarchal regression. Practice-level variables explain most of the variance in the use of e-scripts by physicians, although there are significant differences in use among specialties as well. General internists have slightly lower use rates and pediatricians have the highest rates. Larger practices and multispecialty practices have higher use rates, and five practice culture dimensions influence these rates; two have a negative influence and three (organizational trust, adaptive, and a business orientation) have a positive influence. While previous studies have identified physician characteristics and product deficiencies as factors limiting the use of electronic information technologies in medical practices, our data indicate that the influence of these factors may be highly dependent on the culture of the practice. Consequently, practice administrators can improve physician acceptance and use of these technologies by making sure that there is a culture/technology fit before deciding on a product.


Ruminal availabilities of protein and starch: effects on growth and ruminal and plasma metabolites of dairy calves.
Newborn Holstein calves (n = 75) were blocked by date of birth and sex and assigned randomly to one of eight isonitrogenous starters that contained protein and starch sources of different ruminal availabilities. Soybean meal or soybeans roasted to an exit temperature of 146 degrees C, raw or conglomerated corn, and urea at 1% of DM or no urea were used in a 2 x 2 x 2 factorial arrangement. The conglomeration process consisted of grinding the grain, adding water, pelleting the mixture, and roasting, which increased the degree of starch gelatinization fivefold. Starters were fed for ad libitum intake from 0.5 to 8 wk. Urea supplementation of conglomerated corn starters depressed performance, but the depression was greater when conglomerated corn was used with soybean meal than when it was used with roasted soybeans. Ruminal NH3 and plasma urea increased with increased RDP in starters, but the response varied according to corn type and soy protein source. Urea supplementation depressed plasma Lys, doubled plasma Cit with soybean meal and conglomerated corn starters, but depressed plasma Cit with roasted soybeans and conglomerated corn starters. Conglomerated corn depressed plasma Val and Gly, and roasted soybeans increased plasma Phe. Performance was similar when calves consumed starters containing ruminally synchronous or asynchronous CP and starch sources.


Identification of HLA-A2 restricted CD8(+) T-lymphocyte responses to Plasmodium vivax circumsporozoite protein in individuals naturally exposed to malaria.
Specific CD8(-) T-lymphocyte (CTL) activity against Plasmodium pre-erythrocytic stages (P-ES) derived antigens is considered one of the most important mechanisms for malaria protection. Plasmodium vivax is the second most prevalent human malaria parasite species distributed worldwide. Although several CTL epitopes have been identified in Plasmodium falciparum P-ES derived antigens, none has been described for P. vivax to date. In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast. First, we analysed the prevalence of HLA-A2 allele in the study populations and found that approximately 38 of the individuals expressed this molecule and that 50 of them were HLA-A*0201. We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response. Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay. Specific CD8(-) T-lymphocyte responses were detected for three peptides located in the C-terminal region of the protein. Specific responses to these peptides were also detected in several individuals expressing different HLA-A*02 subtypes. The potential of these peptides to induce specific cytolysis and that of long synthetic peptides comprising these epitopes as P. vivax malaria vaccine subunits are being studied.


Epidemiology and aetiology of acute non-tuberculous salpingitis. A comparison between the early 1970s and the early 1980s with special reference to gonorrhoea and use of intrauterine contraceptive device.
More patients were hospitalised for acute salpingitis at the Department of Obstetrics and Gynaecology, Orebro Medical Centre, Orebro, Sweden, during the 5 year period 1970-1974 (period I) as compared with that of 1980-1984 (period II), 666 patients and 524 respectively, a decrease of 22%. The majority of cases, 92% in period I and 85% in period II, occurred among women 15-34 years of age, that is a relative increase of patients aged over 34 from 8% in period I to 15% in period II. Concomitant urogenital gonorrhoea occurred in 26.2% of the patients in period I compared with 12.0% in period II, a highly significant decrease (p less than 0.001) mainly confined to the age group 15-24, whereas there was no relative difference for the two periods in the age group 25-34 years. The number of patients using intrauterine contraceptive device (IUCD) was 96/666 (14.4%) in period I compared with 113/524 (21.6%) in period II (p less than 0.001). There were also relatively more IUCD users among the patients with gonorrhoea and acute salpingitis in period II (15.5%) compared with period I (10.4%) but this difference was not statistically significant. From 1981 to 1984 370/424 patients were cultured for Chlamydia trachomatis and 27.8% (103/370) were positive. Thus Chlamydia trachomatis is at present, at least in the Orebro area, the most frequently isolated STD agent among acute salpingitis patients while gonorrhoea is of much less importance.


Freeze-dried, plastic-embedded tissue preparation: a review.
The freeze-dried, plastic-embedded specimen is a versatile type of animal soft tissue preparation, with attributes that commend it for some types of analytical and morphological studies. The preparation involves rapid freezing, freeze-drying, osmic acid vapor fixation, and embedding in an epoxy resin. This preparation, though difficult and tedious, offers some advantages for quantification and localization of water-soluble constituents in intracellular spaces. When prepared according to established protocol, there is evidence to suggest that the embedded sample faithfully retains intracellular levels of water-soluble constituents that are present at time of cryofixation. The sample can be stored easily and indefinitely and the tissue can be examined in a variety of ways. Thin sections will accept many stains for light and electron microscopy; the sample can be used for some histochemical procedures; and quantification of intracellular electrolytes is possible with electron probe microanalysis using one of several techniques. A major disadvantage of the method is the lack of satisfactory preservation of normal solute distributions in extracellular spaces. Important considerations for instruments equipped with Si(Li) energy detector systems are the decrease in mass fraction of the elements of interest due to embedding material, and complications in analysis for some elements because of the presence of osmium. This latter problem is of little consequence for analysis by wavelength spectrometers; and the increase in sample density, because of the embedding material, can be used to advantage for thick sample analysis.


Potato phenolics impact starch digestion and glucose transport in model systems but translation to phenolic rich potato chips results in only modest modification of glycemic response in humans.
Beneficial effects of some phenolic compounds in modulation of carbohydrate digestion and glycemic response have been reported, however effects of phenolics from processed potato products on these endpoints are not well known. The aims of this study were to characterize phenolic profiles of fresh potatoes (purple, red, or white fleshed; 2 varieties each) and chips, and to examine the potential for potato phenolic extracts (PPE) to modulate starch digestion and intestinal glucose transport in model systems. Following in vitro assessment, a pilot clinical study (n=11) assessed differences in glycemic response and gastric emptying between chips from pigmented and white potatoes. We hypothesized that phenolics from pigmented potato chips would be recovered through processing and result in a reduced acute glycemic response in humans relative to chips made from white potatoes. PPEs were rich in anthocyanins (~98, 11 and ND mg/100 g dw) and chlorogenic acids (~519, 425 and 157 mg/100 g dw) for purple, red and white varieties respectively. While no significant effects were observed on starch digestion by α-amylase and the α-glucosidases, PPEs significantly (p<0.05) decreased the rate of glucose transport, measured following transport of 1,2,3,4,5,6,6-d7 -glucose (d7-glu) across Caco-2 human intestinal cell monolayers, by 4.5-83.9%. Consistent with in vitro results, consumption of purple potato chips modestly but significantly (p<0.05) decreased blood glucose at 30 and 60 minutes post consumption compared to white chips without impacting gastric emptying. These results suggest that potato phenolics may play a modest role in modulation of glycemic response and these effects may result in subtle differences between consumer products.


Effect of a short antibiotic treatment with roxithromycin on circulating adhesion molecules after coronary stenting: a single-center pilot trial.
The aim of this study was to assess the effect of periprocedural antibiotic treatment with roxithromycin on circulating cell adhesion molecules and restenosis after coronary stent implantation. Case-control study enrolling 25 consecutive patients submitted to coronary stenting for stable, single-vessel coronary artery disease, treated with 300 mg roxithromycin once daily for 5 days, starting 2 days before the procedure (group R). Twenty-five patients, matched for lesion site, length and diameter, as control group (group C). The serological status for Chlamydia pneumoniae (CP) infection (IgG, ELISA) was assessed in all patients. The plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and C-reactive protein at 1 month after coronary stenting were compared with baseline values. Binary restenosis (> or = 50%) was also evaluated at 6 months. sICAM-1 significantly decreased at 1 month in group R vs group C (371 +/- 181 vs 573 +/- 273 ng/ml, p = 0.005). This decrease was more evident in patients with a positive serology for CP (CP+) (group R 373 +/- 131 vs group C 597 +/- 255 ng/ml, p = 0.014). Antibiotic treatment had no effects on circulating E-selectin levels at 1 month (56.7 +/- 97 vs 49.8 +/- 62 ng/ml, p = 0.54). The restenosis rate (9/50, 18%) was similar in the two groups (group R 5/25 [20%], group C 4/25 [16%]). The restenosis rate was similar in the CP+ vs CP- group (6/35 [17%] vs 3/15 [20%]). A short course of treatment with roxithromycin at the time of coronary stenting induces a significant reduction in the sICAM-1 levels at 1 month but apparently does not influence the restenosis rate.


Characterisation of treated effluent from four commonly employed wastewater treatment facilities: A UK case study.
Sewage treatment systems are a common feature across the landscape of the United Kingdom, serving an estimated 96% of the population and discharging approximately eleven billion litres of treated wastewater daily. While large treatment facilities are ubiquitous across the landscape, they are not the only method employed in domestic wastewater treatment. This study investigates whether differences in nutrient export (carbon, nitrogen and phosphorus) and organic matter composition (determined by optical indices, SUVA254, S350-400 and E2:E3) from treated effluent could be detected between four of the most common facilities employed in the treatment of wastewater across the UK. Set in the context of the River Wylye, a small headwater catchment, treatment facilities studied included; a septic tank system, small packet treatment works, and two large sewage treatment works, one of which employed phosphorus stripping for phosphorus removal. Inorganic N and P concentrations ranged between 7.51 and 42.4 mg N l-1 and 0.22 and 8.9 mg P l-1 respectively, with DOC concentrations ranging between 1.63 and 11.8 mg C l-1. Optical indices were comparable to those observed in catchments where organic matter is dominated by autochthonous production, suggesting the dominance of low molecular weight material when compared to values observed across temperate aquatic systems. Combining data from both the Environment Agency and Ordinance Survey we estimate that only 15% of domestic properties not connected to mains sewerage in the study catchment have an Environment Agency consent/exemption permit. This calculation suggests that the quantity of small point sources are significantly underestimated, undermining efforts under current legislation to improve stream ecosystem health.


Can natural language processing be effectively applied for audit data analysis in gynaecological oncology at a UK cancer centre?
The British Gynaecological Cancer Society (BGCS) has highlighted the disparity of ovarian cancer outcomes in the UK compared to other European countries. Therefore, cancer quality assurance audits and subspecialty training are important in improving the UK standard of care for these patients. The current workforce crisis afflicting the NHS creates difficulty in dedicating teams of clinicians to these audits. We present a single institution study to evaluate if NLP-generated code can improve the efficiency of ovarian cancer and subspeciality reaccreditations audits. We used the chat bot Google Bard to write Visual Basic Applications algorithms that utilise Excel files from electronic health records. Primary ovarian cancer data from 2019 to 2022 was retrospectively collected from the Cambridge University Hospital electronic health records. The surgical subspecialty reaccreditation audit analysed the 2022 surgical database. A modular coding approach with Google Bard was applied to generate audit algorithms. The time to complete these current audits was compared against the 2016 ovarian cancer and 2020 subspeciality reaccreditation audits. The previous ovarian cancer audit conducted in 2016 required 3 clinicians for the 135 cases and data collection required 1800 min. Data analysis was completed in 300 min. The current ovarian cancer audit allocated 2 clinicians to the 600 surgical cases. Data collection was completed in 3120 min, 3360 min for code development and 720 min for testing. The 2020 subspecialty reaccreditation audit was completed in 360 min. The 2022 subspecialty reaccreditation audit was completed in 1680 min, with 960 min for code development, 240 for debugging and 480 min for testing. We have demonstrated that NLP-generated code can significantly increase the efficiency of surgical quality assurance audits by eliminating the need for manual data analysis. With the current trajectory of NLP development, increasingly complex algorithms can be developed with minimal programming knowledge.


Conversations between carers and people with schizophrenia: a qualitative analysis using leximancer.
We examined conversations between people with schizophrenia (PwS) and family or professional carers with whom they interacted frequently. We allocated PwS to one of two communication profiles: Low-activity communicators talked much less than their conversational partners, whereas high-activity communicators talked much more. We used Leximancer text analytics software to analyze the conversations. We found that carers used different strategies to accommodate to the PwS's behavior, depending on the PwS's communication profile and their relationship. These findings indicate that optimal communication strategies depend on the PwS's conversational tendencies and the relationship context. They also suggest new opportunities for qualitative assessment via intelligent text analytics technologies.


Old trees bloom new flowers, lysosome targeted near-infrared fluorescent probe for ratiometric sensing of hypobromous acid in vitro and in vivo based on Nile red skeleton.
Hypobromous acid (HOBr), one of the significant reactive oxygen species (ROS) that acts as an important role in human immune system, however the increasing level of HOBr in human body can cause the disorder of eosinophils (EPO), leading to oxidative stress in organelles, and further causing a series of diseases. In this study, a ratiometric fluorescent probe DMBP based on Nile red skeleton was developed to detect HOBr specifically by the electrophilic substitution with HOBr. DMBP emits near-infrared (NIR) fluorescence at 653 nm, after reacting with HOBr, the emission wavelength of DMBP shifted blue and a new peak appeared at 520 nm, realizing a ratiometric examination of HOBr with a limit of detection of 89.00 nM. Based on its sensitive and specific response to HOBr, DMBP was applied in the visual imaging of HOBr in HepG2 cells and zebrafish. Foremost, probe DMBP has excellent lysosome targeting ability and NIR emission reduced the background interference of biological tissues, providing a potential analytical tool to further investigate the role of HOBr in lysosome.


The Spirit Is Willing, But the Flesh is Weak: Why Young People Drink More Than Intended on Weekend Nights-An Event-Level Study.
Heavy alcohol use is common among young adults on weekend nights and is assumed to be intentional. However, little is known about the extent to which heavy consumption is planned prior to the onset of drinking and what factors contribute to drinking more than intended. This study investigates drinking intentions at the beginning of an evening and individual and situational factors associated with a subsequent consumption over the course of multiple nights. Using a smartphone application, 176 young people aged 16 to 25 (mean age = 19.1; 49% women) completed questionnaires on drinking intentions, consumption, and drinking environments before, during, and after multiple Friday and Saturday nights (n = 757). Multilevel regressions were used to investigate individual-level and night-level factors associated with previous drinking intentions and subsequent deviations from intentions. Participants intended to consume 2.5 drinks (SD = 2.8) per night yet consumed 3.8 drinks (SD = 3.9) on average. Drinking intentions were higher among those who frequently went out at night and engaged in more frequent predrinking. Participants drank more than intended on 361 nights (47.7%). For both genders, the number of drinks consumed before 8 pm, attending multiple locations, and being with larger groups of friends contributed to higher consumption than intended at the individual and the night levels. Heavier consumption than intended also occurred when drinking away from home for men and when going to nightclubs for women. Making young adults aware of the tendency to drink more than intended, particularly when drinking begins early in the evening, moves from location to location, and includes large groups of friends, may be a fruitful prevention target. Structural measures, including responsible beverage service, may also help in preventing excessive drinking at multiple locations.


Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.
Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.


Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors.
Type 2 diabetes mellitus (T2DM) is intrinsically connected to overweight and obesity. It is a complex metabolic disorder that predisposes patients to, and is associated with, cardiovascular disease. In addition to the triumvirate of core defects associated with T2DM (involvement of the pancreatic beta cell, the muscle, and the liver), other mechanisms including hyperglucagonemia, accelerated gastric emptying, and incretin deficiency/resistance are also involved. This has led to the development of incretinbased therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. These newer therapies have beneficial effects on glycosylated hemoglobin A1c (HbA1c) levels, weight, and pancreatic beta-cell function.


Amphiphilic random copolymer vesicle induces differentiation of mouse C2C12 myoblasts.
Herein we report that vesicular assembly from a simple non-ionic amphiphilic random copolymer initiates extremely efficient myotube formation from C2C12 myoblast cells in standard growth media lacking horse serum. Control experiments with structurally related polymers and a small molecule suggest the absolute necessity of the vesicular assembly as well as the particular hydrophilic functionality in mediating such high yielding muscle cell generation. The LDH assay indicates that the membrane integrity is retained during cell-cell fusion. Expression of various myogenic factors such as MyoD, myogenin and P-21 has been examined in the presence of the polymersome and control molecules to rationalize this serendipitous discovery.


Thermal effects in the shear-transformation-zone theory of amorphous plasticity: comparisons to metallic glass data.
We extend our earlier shear-transformation-zone theory of amorphous plasticity to include the effects of thermally assisted molecular rearrangements. This version of our theory is a substantial revision and generalization of conventional theories of flow in noncrystalline solids. As in our earlier work, it predicts a dynamic transition between jammed and flowing states at a yield stress. Below that yield stress, it now describes thermally assisted creep. We show that this theory accounts for the experimentally observed strain-rate dependence of the viscosity of metallic glasses, and that it also captures many of the details of the transient stress-strain behavior of those materials during loading. In particular, it explains the apparent onset of superplasticity at sufficiently high stress as a transition between creep at low stresses and plastic flow near the yield stress. We also argue that there are internal inconsistencies in the conventional theories of these deformation processes, and suggest ways in which further experimentation as well as theoretical analysis may lead to better understanding of a broad range of nonequilibrium phenomena.


[Iodine metabolism in leprosy patients (study using a whole-body radiometry method)].
A method of total body radiometry was used to study iodine metabolism in 47 patients with lepromatous leprosy. Disorders were found in 1/3 of the cases. The level of organic iodine in the body was the most informative of all iodine metabolism indices. In the active stage of leprosy it was twice as low, on an average, as the normal one, in the stage of incomplete and stable regression it rose not reaching, however, the values of healthy persons. The lowest mean value of an organic iodine level in the body was observed in patients with noticeable specific polyneuritis. The content of iodine in the thyroid of leprosy patients showed a tendency to a rise starting from the active stage, however it was only in the stages of incomplete and stable regression that it significantly exceeded the normal level. The data obtained should be considered during therapy of lepers to predict and control an unfavorable complication like specific polyneuritis.


Virtues of a worldwide congenital heart surgery database.
The rationale for a congenital heart surgery database lies in the organized manner in which information can be compiled to accomplish programmatic evaluation, monitor clinical outcomes, comply with governmental requirements, perform retrospective and prospective clinical studies, and participate in local, national, and global improvement strategies. The task of inaugurating an effective congenital heart surgery database has taken many years and involved concurrent development efforts at multiple sites. Two such efforts took place in North America with the Society of Thoracic Surgeons Congenital Heart Surgery Database, and in Europe with the European Congenital Heart Defects Database. These initial efforts provided the impetus for development of an international congenital heart surgery database that would allow scientific exchanges on an international scale and promote multi-institutional evaluation of congenital heart surgery. Sample outcome templates from the Society of Thoracic Surgeons and the European Association for Cardio-thoracic Surgery's accepted minimum database data set are reviewed for the specific diagnostic entry ventricular septal defect, to familiarize the reader with potential available data summaries and outcome analyses, including risk stratification, when data harvest is performed. In Europe, the agreed upon minimum data set are now collected as part of the Pediatric European Cardiac Surgical Registry, while in North America users of the CardioAccess database and users of the minimum data set downloaded from the Society of Thoracic Surgeons web site are being notified of plans for a 2002 data harvest incorporating the minimum database data set. It is likely that the extant voluntary, minimal data set congenital heart surgery database will be replaced by a mandated system required by states, provinces, and countries. Data collection schemes and data validation programs will become standardized, which will result in improved data quality and uniform congenital heart center participation. As participation with valid data approaches 100% of congenital heart centers, the power and importance of the database increases exponentially. Reliable information can be used to assess residency/fellowship programs, resource allocation, major therapeutic trends, manpower issues, and in the end, all initiatives that will require accurate information.


Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma.
Renal cell carcinoma (RCC) is the most common malignancy in the kidney. Antiangiogenic targeted therapies inhibit the progression of RCC, but have limited impacts on invasion or metastasis of tumor cells. Integrin-linked kinase (ILK) is a serine/threonine kinase implicated in the regulation of cell growth/survival, cell-cycle progression, epithelial-mesenchymal transition (EMT), invasion/migration, and angiogenesis. However, the role of ILK in RCC has not been evaluated. We investigated the role of ILK on cancer progression and metastasis and the therapeutic potential of ILK inhibition in RCC. Our investigation reveals that ILK is expressed at a low level in normal cells and low-stage RCC cells and is highly expressed in advanced and metastatic cells. Caki-1, a metastatic RCC cell line, showed higher expression of molecular EMT markers, including Snail and Zeb1, but decreased activity of GSK3β. Knockdown of ILK using small interference (si)-ILK minimally inhibited tumor proliferation and cell-cycle progression was not significantly affected. However, ILK knockdown suppressed the formation of stress fibers and focal adhesions and impeded phenotypic EMT markers, including cell migration and invasion, in Caki-1 and UMRC-3 cells. Finally, in vivo knockdown of ILK suppressed the progression, invasion, and metastasis of primary RCC in nude mice by downregulation of EMT markers (Snail, Zeb1, vimentin, and E-cadherin). Our results show that ILK may be essential for invasion and metastasis in RCC and regulates vimentin and E-cadherin expression by regulating the EMT-related transcription factors Snail and Zeb1. These results suggest that ILK may be a potential target in RCC.


Effect of Fluoride Concentration on Reduction of Enamel Demineralization According to the Cariogenic Challenge.
Fluoride present in toothpaste at 1,100 µg/g is considered effective on caries control. However, under high cariogenic challenge due to increasing sugar exposure, higher fluoride concentration (5,000 µg/g) could be necessary to compensate the unbalance on caries process. This was tested in a pH-cycling regimen, which evaluated the effect of fluoride concentration relative to toothpaste on reduction of enamel demineralization under conditions of two levels of cariogenic challenge. Enamel slabs (n=20) were subjected to two pH-cycling regimens, simulating 8x and 16x/day sugar exposure and were treated with solutions containing: 0 (no fluoride), 275 or 1,250 µg F/mL, resulting in 6 treatment groups: 4-h/0-F; 8-h/0-F; 4-h/275-F; 8-h/275-F; 4-h/1,250-F and 8-h/1,250-F. The 275 and 1,250 µg F/mL concentrations simulate mouth salivary dilution when 1,100 and 5,000 µg/g toothpastes are used. Enamel demineralization was assessed by surface (%SHL) and cross-sectional hardness. Fluoride taken up by enamel was also evaluated. Data were analyzed by ANOVA one-way and Tukey's test. The treatment with 1,250 µg F/mL significantly reduced %SHL compared with 275 µg F/mL (p<0.05), irrespective the level of cariogenic challenge (4-h/1,250-F vs. 4-h/275-F and 8-h/1,250-F vs 8-h/275-F comparisons, respectively). These data were supported by fluoride concentration found in enamel. These findings suggest that higher fluoride concentrations could partly compensate the greater caries risk under higher cariogenic challenge due to increasing sugar exposure.


Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe.
Group A rotaviruses can infect both humans and animals. Individual rotavirus strains can occasionally cross species barriers and might hereby contribute to the emergence of new genotypes in heterologous hosts. The incidence and impact of zoonotic rotavirus are not well defined, and one reason for this is a lack of data about strains circulating in suspected reservoir animal hosts. In this study we report the incidence, genetic diversity, and molecular epidemiology of rotaviruses detected in domestic cattle and swine in 6 European countries. From 2003 to 2007, 1101 and more than 2000 faecal specimens were collected from swine and cattle, both healthy and diarrhoeic, and tested for rotaviruses. Viruses from positive stools were genotyped and a subset of strains was characterized by nucleotide sequencing and phylogenetic analysis of the VP7 (G) and VP4 (P) genes. Rotaviruses were detected in 43% of bovine samples and in 14% of porcine samples. In cattle, 10 different combinations of G and P types were identified and the most common strains were G6P[11] and G6P[5]. In swine, the number of identified G-P combinations was higher (n=21), however, no single combination was predominant across Europe. Newly described genotype specificities, P[27] and P[32], were identified in swine. When compared at the nucleotide sequence level, the identified porcine rotavirus strains and contemporary human strains grouped together phylogenetically, whereas bovine rotavirus strains formed separate clades. These data demonstrate large genetic diversity of porcine and bovine rotavirus strains across Europe, and suggest that livestock herds may serve as potential reservoirs for human infections.


Optical manipulation and defect creation in a liquid crystal on a photoresponsive surface.
Light-induced modulations of the refractive index and pattern formation are desirable to generate complex photonic structures via exposure to light. Here we show that local modulations of the effective refractive index and reconfigurable defects can be locally induced in a hybridized thin birefringent film of a nematic liquid crystal (LC) on a photoresponsive (generating photoinduced electric fields) iron doped lithium niobate surface via exposure to a focused laser beam. Samples were studied with a tailored imaging approach, which provided the ability to investigate these optically excited, field-induced responses on a microscopic level. Upon exposure with a focused laser beam, the fluent LC was expanded on the substrate's surface and localized field-induced defects were optically created. Both umbilic (central) and line defects were observed. The formation of field-induced umbilic defects was modeled in numerical simulations. In addition, line defects were experimentally studied. It was seen that line defects interconnected the centers of two central defects (field-induced defects, which were present at the upper and lower surfaces of the LC layer). In addition, line disclinations separating reverse tilt domains (caused by the inhomogeneous distribution of the photogenerated fields) were seen. These line disclinations were pinned to the central defects. By exposure with two adjacent focused laser beams two umbilic defects were created side by side and interconnected with a line defect (the line defects pinned to each umbilic defect were joined in a single defect line). An alternative technique is presented to field-induce promising photonic motives (microlenses, resonators, line defects) in a liquid crystalline, hybridized birefringent film on a microscopic scale by using a low-power laser (opposed to the high power necessary to induce optical Kerr responses in a neat LC).


[Clinico-dynamic features of neurotic and psychotic hysterical depressions in the late period of craniocerebral injuries].
Twenty patients with neurotic and twenty patients with psychotic hysterical depressions developing in the presence of long-term consequences of craniocerebral injuries were subjected to a comparative examination. Differences and transitions between these two conditions are not a uniform intensification of a definite set of symptoms but present a qualitative transformation of the status with extension of disorders to all spheres of mental activity.


Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.
In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.


[The definition of chronic kidney disease in a context of aging population].
Chronic kidney disease (CKD) is a progressively chronic disease that carries a high burden of morbidity and mortality and is associated with significant healthcare utilization and costs. Recent trends shown that the prevalence of CKD is stable in Europe and USA, whereas tends to decline in some countries with a high standard of care. According to international guidelines, chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (eGFR) less than 60 ml/min. This staging method has a main drawback, its imprecise assessment of renal function at the extremes of the age bracket: the use of a fixed threshold value (glomerular filtration rate [GFR <60 ml /min]) to define chronic renal failure appears an imprecise measure in the young and in the elderly. In these two groups, in fact, the measurement of GFR is difficult to categorize in a "rigid" system of classification. The reduction of the GFR with aging is due to a complex process that leads to a steady reduction of the functioning nephrons over 40 years of age. Taken together, these findings should spur us to adopt a new definition of CKD. An age-adapted definition of CKD could be a good solution to avoid a diagnosis of CKD in elderly patients (GFR >45 ml/min) when there are no prognostic implications on survival. The adoption of this new definition would also reduce the high prevalence of the disease in the general population, with a beneficial reduction of the costs associated with monitoring a mildly decreased eGFR.


Predictors of Nocturnal Hypoxemic Burden in Patients Undergoing Elective Coronary Artery Bypass Grafting Surgery.
Background: Nocturnal hypoxemia has been linked to increased cardiovascular morbidity and mortality. Several common diseases, such as sleep-disordered breathing (SDB), heart failure (HF), obesity, and pulmonary disease, coincide with an elevated nocturnal hypoxemic burden with and without repetitive desaturations. Research question: This study aimed to evaluate the association of relevant common diseases with distinctive metrics of nocturnal hypoxemic burden with and without repetitive desaturations in patients undergoing coronary artery bypass grafting surgery. Study design and methods: In this subanalysis of the prospective observational study, CONSIDER-AF (NCT02877745) portable SDB monitoring was performed on 429 patients with severe coronary artery disease the night before cardiac surgery. Pulse oximetry was used to determine nocturnal hypoxemic burden, as defined by total recording time spent with oxygen saturation levels < 90% (T90). T90 was further characterized as T90 due to intermittent hypoxemia (T90desaturation) and T90 due to nonspecific and noncyclic SpO2-drifts (T90non-specific). Results: Multivariable linear regression analysis identified SDB (apnea-hypopnea-index ≥ 15/h; B [95% CI]: 6.5 [0.4; 12.5], p = 0.036), obesity (8.2 [2.5; 13.9], p = 0.005), and mild-to-moderate chronic obstructive pulmonary disease (COPD, 16.7 [8.5; 25.0], p < 0.001) as significant predictors of an increased nocturnal hypoxemic burden. Diseases such as SDB, obesity and HF were significantly associated with elevated T90desaturation. In contrast, obesity and mild-to-moderate COPD were significant modulators of T90non-specific. Interpretation: SDB and leading causes for SDB, such as obesity and HF, are associated with an increased nocturnal hypoxemic burden with repetitive desaturations. Potential causes for hypoventilation syndromes, such as obesity and mild-to-moderate COPD, are linked to an increased hypoxemic burden without repetitive desaturations. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02877745.