Epidemiological and genetic study of exertional rhabdomyolysis in a Warmblood horse family in Switzerland.
Exertional rhabdomyolysis (ER) and its familial basis in Warmblood horses is incompletely understood. To describe the case details, clinical signs and management of ER-affected Warmblood horses from a family with a high prevalence of ER, to determine if histopathological signs of polysaccharide storage myopathy (PSSM) and the glycogen synthase (GYS1) mutation are associated with ER in this family, and to investigate potential risk factors for development of ER. A family consisting of a sire with ER and 71 of his descendants was investigated. History of episodes of ER, husbandry, feeding and use was assessed by interviewing horse owners using a standardised questionnaire. All horses were genotyped for GYS1. In 10 ER-affected horses, muscle histopathology was evaluated. Signs of ER were reported in 39% of horses and 51% of the entire family possessed the GYS1 mutation. Horses possessing the GYS1 mutation had a 7.1-times increased risk for developing ER compared to those with the normal genotype (95% confidence interval [CI] 2.37-21.23, P = 0.0005). All muscle samples from horses in the family with ER showed polysaccharide accumulation typical for PSSM, amylase-resistant in 9/10 cases. There was evidence (odds ratio 5.6, CI 1.00-31.32, P = 0.05) that fat or oil feeding improved clinical signs of ER. No other effects of environmental factors associated with clinical signs of ER were identified. PSSM associated with the GYS1 mutation is one identifiable cause of ER in Warmblood horses. Signs of ER are not always manifest in GYS1 positive horses and there are also other causes for ER in Warmblood horses. Breeding animals with the GYS1 mutation results in a high prevalence of ER due to its dominant mode of inheritance.


Ropivacaine, a new amide-type local anesthetic agent, is metabolized by cytochromes P450 1A and 3A in human liver microsomes.
Ropivacaine is a new amide-type local anesthetic agent. Unlike bupivacaine and mepivacaine, two structurally similar local anesthetic compounds, ropivacaine is exclusively the S-(-)-enantiomer. Ropivacaine is predominantly eliminated by extensive metabolism in the liver, with only 1% of the dose being excreted unchanged in the urine of humans. Four of the metabolites formed in human liver microsomes were identified as 3-OH-ropivacaine, 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and 2',6'-pipecoloxylidide (PPX). The enzymes involved in the human metabolism of ropivacaine have not been identified. To ascertain which forms of cytochrome P450 are involved, ropivacaine was incubated with human microsomes from 10 different livers having different cytochrome P450 activities. A strong correlation was found between the formation of 3-OH-ropivacaine and CYP1A (r = 0.87-0.89) and between the formation of 4-OH-ropivacaine, 2-OH-ropivacaine, and PPX and CYP3A (r = 0.97-1). Incubation of ropivacaine and human liver microsomes in the presence of alpha-naphthoflavone or furafylline, inhibitors of CYP1A, decreased the formation of 3-OH-ropivacaine by about 85%, without affecting the formation of the other metabolites. The formation of 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and PPX was markedly inhibited in the presence of troleandomycin, an inhibitor of CYP3A. Microsomes from cells expressing CYP1A2 formed 3-OH-ropivacaine, whereas 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and PPX were formed in microsomes from cells expressing CYP3A4. Inhibitors of CYP2C (sulfaphenazole), CYP2D6 (quinidine), and 2E1 (diethyldithiocarbamate) did not inhibit the formation of any metabolite from ropivacaine. In conclusion, CYP1A catalyzes the formation of 3-OH-ropivacaine, the main metabolite formed in vivo, whereas the formation of 4-OH-ropivacaine, 2-OH-methyl-ropivacaine, and PPX was catalyzed by CYP3A.


Comparative outcome of different treatment options for fragility fractures of the sacrum.
Fragility fractures of the sacrum (FFS) have been detected more and more frequently in recent times, and the incidence will continue to increase due to increasing life expectancy. The aim of this study was to compare the clinical outcome of conservative, interventional and surgical treatment of FFS. Retrospectively, 292 patients (276 women, 16 men) with confirmed FFS were followed up over a period of 2 years. The age of the women was Ø 81.2 (58 - 99) and that of the men Ø 78.1 (76 - 85) years. The pain was quantified using a VAS. Fractures were classified in accordance with the Rommens and Hofmann and with the Denis classification using conventional X-rays, CT and MRI. A QCT of the lumbar spine was performed to quantify bone mineral density. Concomitant diseases of every patient were recorded. An interdisciplinary case conference determined the individual treatment concept considering the age, type of fracture, pain level and comorbidities with classification into conservative, interventional (any type of sacroplasty) or surgical treatment. Over the course pain and independence were measured, complications and patient satisfaction were documented. A vitamin D determination was done, and existing comorbidities were included. Patients with a pain level of ≤5 benefited from the conservative therapy measures, with pain levels > 5 significantly delaying the development of mobility. After sacroplasty, the pain reduced significantly, which caused a rapid improvement in mobility without any significant difference being found between vertebro- (VSP), balloon (BSP), radiofrequency (RFS) and cement sacroplasty (CSP). In terms of pain reduction and mobilization, the surgical treated patients benefited from osteosynthesis, although more complex fracture types with lumbopelvic stabilization took longer. Overall, there were no deaths during the hospital stay. Mortality after 12 months was 21.7% for the conservative, 8.4% for the interventional and 13.6% for the surgical therapy group; the differences are significant. For patients in the conservative therapy group who were difficult to mobilize due to pain, the mortality increased to 24.3%. Over 24 months, patients achieved the best independence after sacroplasty. At 12 and 24 months, subjective satisfaction with the therapies was best after sacroplasty, followed by osteosynthesis and conservative measures. All patients had a pronounced vitamin D deficiency and manifest osteoporosis. Cardiovascular pathologies were the main concomitant diseases. Patients with FFS with a low level of pain benefit from conservative therapy measures, whereby complications and mortality increase significantly in the case of persistent immobilizing pain. Patients with an unacceptable level of pain resulting from non-dislocated fractures benefit significantly from sacroplasty. Patients with unstable and displaced fractures (Rommens and Hofmann type III and IV) should be operated on promptly. Different techniques are available for sacroplasty and osteosynthesis, which lead to an improvement of independence and a reduction in mortality.


An Outcomes Study on the Effects of the Singapore General Hospital Burns Protocol.
The Singapore General Hospital Burns Protocol was implemented in May 2014 to standardize treatment for all burns patients, incorporate new techniques and materials, and streamline the processes and workflow of burns management. This study aims to analyze the effects of the Burns Protocol 2 years after its implementation. Using a REDCap electronic database, all burns patients admitted from May 2013 to April 2016 were included in the study. The historical preimplementation control group composed of patients admitted from May 2013 to April 2014 (n = 96). The postimplementation prospective study cohort consisted of patients admitted from May 2014 to April 2016 (n = 243). Details of the patients collected included age, sex, comorbidities, total body surface area (TBSA) burns, time until surgery, number of surgeries, number of positive tissue and blood cultures, and length of hospital stay. There was no statistically significant difference in the demographics of both groups. The study group had a statistically significant shorter time to surgery compared with the control group (20.8 vs 38.1, P < 0.0001). The study group also averaged fewer surgeries performed (1.96 vs 2.29, P = 0.285), which, after accounting for the extent of burns, was statistically significant (number of surgeries/TBSA, 0.324 vs 0.506; P = 0.0499). The study group also had significantly shorter length of stay (12.5 vs 16.8, P = 0.0273), a shorter length of stay/TBSA burns (0.874 vs 1.342, P = 0.0101), and fewer positive tissue cultures (0.6 vs 1.3, P = 0.0003). The study group also trended toward fewer positive blood culture results (0.09 vs 0.35, P = 0.0593), although the difference was just shy of statistical significance. The new Singapore General Hospital Burns Protocol had revolutionized Singapore burns care by introducing a streamlined, multidisciplinary burns management, resulting in improved patient outcomes, lowered health care costs, and improved system resource use.


Nitric oxide regulates polarity of guinea pig distal colon pellet propagation and circular muscle motor response.
Peristaltic reflex does not fully explain the polarity of peristalsis. In the distal colon, we propose that the balance of circular muscle contraction proximal and distal to the pellet is a local reflex that predicts polarity of peristalsis. Guinea pig distal colon segments were harvested, and fecal pellet transit was measured. Photographs of fecal pellet propagation were taken, colonic radius proximal and distal to the moving pellet was measured, and the ratio of radius proximal to pellet to radius distal to pellet was measured. Isometric transducers were attached 1 cm proximal and distal to a fixed intraluminal balloon, and circular muscle (CM) response to balloon distension was recorded. N (G)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) was used to elicit an effect in experimental preparations and compared to controls. Fecal pellet transit was delayed after L-NAME treatment (163 ± 23.9 vs. 41.5 ± 1.9 s in control, n = 6, p < 0.001). Photo-analysis revealed a ratio of proximal/distal colonic radius in control colon to be 0.72 ± 0.02 (n = 17) and in L-NAME treated colon 1.0 ± 0.02 (n = 10, p < 0.01). The dominant CM response pattern was a large contraction proximal to the inflated balloon and a smaller contraction distal to the balloon. In the presence of L-NAME, distal contraction was larger than the proximal contraction in 66% of the experiments. Pellet propulsion in the guinea pig's distal colon depends on nitric oxide to provide appropriate balance of force between proximal and distal contraction, resulting in pellet propagation toward the anus. CM contracts both proximal and distal to the pellet, and the polarity of pellet progression depends on the balance of the two forces.


Corticomedullary shunting after ischaemia and reperfusion in the porcine kidney?
Renal perfusion may redistribute from cortex to medulla during systemic hypovolaemia and after renal ischaemia for other reasons, but there is no consensus on this matter. We studied renal perfusion after renal ischaemia and reperfusion. Renal perfusion distribution was examined by use of 153Gadolinium-labeled microspheres (MS) after 2 h (hrs) and 4 h ischaemia of the pig kidney followed by 4 h of reperfusion. Intra-arterial injected MS are trapped in the glomeruli in renal cortex, which means that MS are not present in the medulla under normal physiological conditions. Visual evaluation after reperfusion demonstrated that MS redistributed from the renal cortex to the medulla in 6 out of 16 pigs (38%) subjected to 4 h ischaemia and in one out of 18 pigs subjected to 2 h ischaemia. Central renal uptake of MS covering the medullary/total renal uptake was significantly higher in kidneys subjected to 4 h ischaemia compared with pigs subjected to 2 h ischaemia (69 ± 5% vs. 63 ± 1%, p < 0.001), and also significantly higher than in the contralateral kidney (69 ± 5% vs. 63 ± 2%, p < 0.001). Analysis of blood and urine demonstrated no presence of radioactivity. The study demonstrated the presence of MS in the renal medulla in response to renal ischaemia and reperfusion suggesting that severe ischaemia and reperfusion of the pig kidney leads to opening of functional shunts bypassing glomeruli.


Prenatal Echocardiographic Assessment of Foramen Ovale Appearance in Fetuses with D-Transposition of the Great Arteries and Impact on Neonatal Outcome.
Neonates with D-transposition of the great arteries (dTGA) may die at birth because of the inadequate intracardiac mixing due to a misdiagnosed restrictive foramen ovale. We reviewed our experience in echocardiographic assessment and perinatal management of fetuses with dTGA searching for new features that may predict the need for urgent balloon atrial septostomy (BAS) immediately after birth. We included fetuses diagnosed with dTGA between January 2000 and December 2014. We assessed pre- and postnatal appearance of the foramen ovale, ductus arteriosus and pulmonary veins. Both the diagnostic findings at the time of last prenatal echocardiogram and those findings deriving from a retrospective reevaluation of stored videos were considered. BAS was defined as urgent if performed in neonates with restrictive foramen ovale and severe hypoxemia. We reviewed 40 fetuses with dTGA. 20/40 fetuses received urgent BAS at birth. Not only the restrictive but also the hypermobile and the redundant appearance of the foramen ovale was significantly associated with urgent BAS (p < 0.0001, p = 0.002 and p = 0.0001, respectively). Prenatal evaluation of the foramen ovale appearance in fetuses with dTGA is still challenging. Based on our experience, also the redundant foramen ovale appearance may need urgent BAS at birth.


Effect of PTTG on endogenous gene expression in HEK 293 cells.
Pituitary tumor transforming gene (PTTG), also known as securin, is highly expressed in various tumors including pituitary, thyroid, colon, ovary, testis, lung, and breast. An overexpression of PTTG enhances cell proliferation, induces cellular transformation in vitro, and promotes tumor development in nude mice. PTTG also inhibits separation of sister chromatids leading to aneuploidy and genetic instability. A great amount of work has been undertaken to understand the biology of PTTG and its expression in various tumors. However, mechanisms by which PTTG mediates its tumorigenic function are not fully understood. To utilize this gene for cancer therapy, identification of the downstream signaling genes regulated by PTTG in mediation of its tumorigenic function is necessary. For this purpose, we expressed PTTG in human embryonic kidney (HEK293) cells that do not express PTTG and analyzed the downstream genes using microarray analysis. A total of 22,277 genes printed on an Affymetrix HG-U133A 2.0 GeneChip array were screened with labeled cRNA prepared from HEK293 cells infected with adenovirus vector expressing PTTG cDNA (AdPTTG cDNA) and compared with labeled cRNA prepared from HEK293 cells infected with control adenovirus (control Ad) or adenovirus vector expressing GFP (AdGFP). Out of 22,277 genes, 71 genes were down-regulated and 35 genes were up-regulated with an FDR corrected p-value of < or = 0.05 and a fold change of > or =2. Most of the altered genes identified are involved in the cell cycle and cell apoptosis; a few are involved in mRNA processing and nitrogen metabolism. Most of the up-regulated genes belong to the histone protein family. PTTG is a well-studied oncogene for its role in tumorigenesis. In addition to its importance in regulation of the cell cycle, this gene has also been recently shown to play a role in the induction of cell apoptosis. The microarray analysis in the present study demonstrated that PTTG may induce apoptosis by down-regulation of oncogenes such as v-Jun and v-maf and up-regulation of the histone family of genes.


What puts the 'yuck' in the yuck factor?
The advances in biotechnology have given rise to a discussion concerning the strong emotional reaction expressed by the public towards biotechnological innovations. This reaction has been named the 'Yuck-factor' by several theorists of bioethics. Leon Kass, the former chairman of the President's council on bioethics, has appraised this public reaction as 'an emotional expression of deep wisdom, beyond reason's power fully to articulate it'.(1) Similar arguments have been forwarded by the Catholic Church, several Protestant denominations and the Pro-Life movement. Several bioethicists have, however, opposed the idea of a disgust-based morality.(2) Recent findings in cognitive science support the view that the strong negative emotions people often experience when faced with biotechnological ideas are not expressions of inner wisdom. The negative emotions may rather be the result of a cognitive violation the biotechnological innovations easily cause. Due to their evolutionary background, people have certain automatic and quick cognitive tendencies routinely used for categorizing and reasoning about nature, usually termed 'folk biology'. Biotechnological processes like hybridisation and cloning clearly violate several of the cognitive rules people naturally apply for the explanation and categorization of their natural environment. As the cognitive tendencies routinely applied to the explanation of biological world are violated, an emotional response of fear, disgust and of something unnatural being underway is easily provoked. It is suggested in this paper that the reason behind the Yuck-factor is not a deep inner wisdom, but a violation of natural human cognitive tendencies concerning the biological world.


A Single Belief-Changing Psychedelic Experience Is Associated With Increased Attribution of Consciousness to Living and Non-living Entities.
Although the topic of consciousness is both mysterious and controversial, psychedelic drugs are popularly believed to provide unique insights into the nature of consciousness despite a lack of empirical evidence. This study addresses the question of whether psychedelics change the attribution of consciousness to a range of living and non-living entities. A survey was conducted in 1,606 respondents who endorsed a belief changing psychedelic experience. Participants rated their attributions of consciousness to a range of living and non-living entities before and after their psychedelic experience. Superstitious beliefs and belief in freewill were also assessed. From before the experience to after, there were large increases in attribution of consciousness to various entities including non-human primates (63-83%), quadrupeds (59-79%), insects (33-57%), fungi (21-56%), plants (26-61%), inanimate natural objects (8-26%), and inanimate manmade objects (3-15%). Higher ratings of mystical experience were associated with greater increases in the attribution of consciousness. Moreover, the increased attributions of consciousness did not decrease in those who completed the survey years after the psychedelic experience. In contrast to attributions of consciousness, beliefs in freewill and superstitions did not change. Notably, all findings were similar when restricted to individuals reporting on their first psychedelic experience. This study demonstrates that, among people who reported belief-changing psychedelic experiences, attribution of consciousness to various entities increases. Future prospective psychedelic drug administration studies that control for expectancies are needed.


Role of neuregulin-1 beta in the developing lung.
Neuregulins play a critical role in the developing heart, nervous, and mammary systems. Neuregulin-1-induced cardiac, neuronal, and mammary differentiation is based on a cell-cell communication model, where the ligand neuregulin-1 is produced and secreted by one cell type, which does not express its receptors erbB3 and erbB4 and acts on neighboring cell types that do express these receptors. We proposed that neuregulin-1 affects fetal lung maturation through a similar mechanism. Immunostaining showed neuregulin-1 in fetal lung that increased in fibroblasts at the onset of surfactant synthesis. Neuregulin-1 beta was found to be secreted by the fetal lung fibroblast and stimulated type II cell surfactant synthesis. Both fetal lung fibroblast-conditioned media and neuregulin-1 stimulated erbB2 receptor phosphorylation in type II cells. The effects of neuregulin-1 and of fibroblast-conditioned media on both surfactant synthesis and type II cell erbB2 phosphorylation were specifically blocked by antibody to neuregulin-1. Thus, neuregulin-1 beta may control fetal lung maturation through mesenchymal-epithelial interactions in a paracrine mechanism similar to that described for the developing heart, brain, and mammary systems.


Convex triangular vs. cylindrical field of view: how does the shape of the FOV affect radiation dose?
To compare the dosimetry between convex triangular fields of view (FOV) and similar dimension cylindrical FOVs of two cone-beam computed tomography (CBCT) models. Optically stimulated luminescence dosimeters (OSLDs) were placed in fiducial anatomical locations in an anthropomorphic phantom representing an adult head male for dosimetry scans. Convex triangular FOVs (100 × 80 mm/maxilla-mandible; 100 × 50 mm mandible; 100 × 50 mm/maxilla) from Veraviewepocs 3D R100 (J. Morita, Kyoto, Japan) (R100) and Veraview® X800 (J. Morita, Kyoto, Japan) (X800) and cylindrical FOVs from R100 and X800 (80 × 80 mm/maxilla-mandible; 80 × 50 mm/mandible; 80 × 50 mm/maxilla) were obtained, resulting in 12 different scan protocols. Equivalent doses for each relevant organ/tissue and the effective dose for each protocol were calculated. Mean effective doses were compared by the two-way analysis of variance (ANOVA) with Tukey's post hoc test to evaluate the effect of the FOV and device (α = 0.05). The effective doses ranged between 69 and 324 μSv for the convex triangular FOVs and 76 and 332 μSv for the cylindrical FOVs. Convex triangular FOVs from the R100 device had effective doses 2.3 to 15.3% lower than their corresponding cylindrical FOVs with similar height (p < 0.05), and that difference ranged between 8.8 and 11.8% for the X800 device (p < 0.05). Convex triangular fields of view delivered slightly lower effective doses than the cylindrical fields of view of similar dimensions in the R100 and X800 CBCT devices. Understanding the influence of the image geometry formation in effective dose allows optimization to reduce patient dose.


Sideline Concussion Assessment: The Current State of the Art.
More than 200 million American adults and children participate in organized physical activity. Growing awareness has highlighted that concussion, especially when repeated, may be associated with prolonged neurological, cognitive, and/or neuropsychiatric sequelae. Objective diagnosis of concussion remains challenging. Although some concussion symptoms may be apparent even to nonmedical observers, diagnosis and removal from play for evaluation depend on validated assessment tools and trained, vigilant healthcare personnel. Over the past 2 decades, sideline concussion measures have undergone significant revision and augmentation to become more comprehensive batteries in order to detect a wide spectrum of symptomatology, eg, neurocognitive function, postconcussive symptoms, gait/balance, and saccadic eye movements. This review summarizes the current state-of-the-art concussion evaluation instruments, ranging from the Sports Concussion Assessment Tool (SCAT) and tools that may enhance concussion detection, to near-term blood-based biomarkers and emerging technology (eg, head impact sensors, vestibulo-ocular/eye-tracking, and mobile applications). Special focus is directed at feasibility, utility, generalizability, and challenges to implementation of each measure on-field and on the sidelines. This review finds that few instruments beyond the SCAT provide guidance for removal from play, and establishing thresholds for concussion detection and removal from play in qualification/validation of future instruments is of high importance. Integration of emerging sideline concussion evaluation tools should be supported by resources and education to athletes, caregivers, athletic staff, and medical professionals for standardized administration as well as triage, referral, and prevention strategies. It should be noted that concussion evaluation instruments are used to assist the clinician in sideline diagnosis, and no single test can diagnose concussion as a standalone investigation.


A versatile petri net based architecture for modeling and simulation of complex biological processes.
The research on modeling and simulation of complex biological systems is getting more important in Systems Biology. In this respect, we have developed Hybrid Function Petri net (HFPN) that was newly developed from existing Petri net because of their intuitive graphical representation and their capabilities for mathematical analyses. However, in the process of modeling metabolic, gene regulatory or signal transduction pathways with the architecture, we have realized three extensions of HFPN, (i) an entity should be extended to contain more than one value, (ii) an entity should be extended to handle other primitive types, e.g. boolean, string, (iii) an entity should be extended to handle more advanced type called object that consists of variables and methods, are necessary for modeling biological systems with Petri net based architecture. To deal with it, we define a new enhanced Petri net called hybrid functional Petri net with extension (HFPNe). To demonstrate the effectiveness of the enhancements, we model and simulate with HFPNe four biological processes that are diffcult to represent with the previous architecture HFPN.


Policy directions to promote healthy dietary patterns in Canada.
The effective promotion of healthy dietary patterns rests on a supportive policy environment. Given the vast, ever-expanding selection of foods in Canadian supermarkets and the proliferation of nutrition-related food marketing, more effective communication tools are needed to help consumers understand food selections within the context of a total diet. In addition, policy actions at the federal, provincial, and municipal levels are needed to lift economic and geographic barriers to food access for specific population subgroups.


A mind-body lifestyle intervention enhances emotional control in patients with major depressive disorder: a randomized, controlled study.
To investigate the effects of the Dejian mind-body intervention (DMBI), on depressive symptoms and electroencephalography (EEG) changes in relation to emotional processing in patients with depression. Seventy-five age-, gender-, and education-matched participants with depression were randomly assigned to receive either Cognitive Behavior Therapy (CBT) or DMBI or were placed in a control group. Overall depressive syndrome, specific mood-related symptoms (Hamilton Psychiatric Rating Scale for Depression, Beck Depression Inventory), and EEG data were collected individually during a resting state and during affective image viewing before and after 10 weeks of intervention. After intervention, both the DMBI and CBT groups showed significantly reduced levels of overall depressive syndrome and mood-related symptoms (Ps ≤ 0.002) than the control group. In addition, the DMBI group demonstrated a significantly greater extent of elevation in fronto-posterior EEG theta coherence on the right hemisphere when viewing different mood-induction (neutral, positive, and negative) stimuli than the CBT and control groups (Ps < 0.03). The elevated intra-right fronto-posterior coherence when viewing mood-induction stimuli correlated with improved mood levels after the intervention (Ps < 0.05). Our findings also showed that, only in the DMBI group, there was a significant suppression of theta source activity at the posterior and subcortical brain regions that are known to mediate negative emotional responses and the self-absorbed mode of thinking. The findings of reduced depressive symptoms and elevated frontoposterior coherence suggest that the DMBI can enhance emotional control in depression.


[Citrulline extracellular level in the nucleus accumbens during acquisition and extinction of classical conditioned fear response with pain reinforcement].
By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular levels of citrulline (NO co-product) and arginine (NO precursor) increase in the rat n. accumbens during acquisition and expression of a classical fear response. The conditioned rise of citrulline and arginine levels gradually decreased in the course of extinction. The renewal of the response produced an increase in extracellular citrulline and arginine levels. These data suggest that the acquisition of conditioned fear response causes an increase in NO production in the n. accumbens that weakens during the extinction and is restored during the reinstatement of the response.


[Genetic epidemiology: an expanding scientific discipline].
Genetic epidemiology is a relatively new discipline that studies the interaction between genetic and environmental factors in the production of human diseases. Taking advantage of the genetic markers provided by molecular biological research, complex computerized algorithms, and large databases, the field of genetic epidemiology has undergone notable development in the past 10 years. This article describes the objectives and methodology of genetic epidemiology, using concrete examples from the recent scientific literature.


Starvation response and growth in serum of Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia, and Pseudoramibacter alactolyticus.
The microbiota inhabiting the untreated root canal differ markedly from those found in post-treatment disease, yet there is limited information on the microbial characteristics distinguishing the different infections. We hypothesized that starvation survival is a key microbial property in species selection. This study analyzed starvation-survival behavior over 60 days of species representative of the untreated root canal infection: Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia and Pseudoramibacter alactolyticus. All species did not survive 1 day in water. In 1% serum, the 4 species could not survive beyond 2-3 weeks. They required a high initial cell density and >or=10% serum to survive the observation period. The results highlight a poor starvation-survival capacity of these 4 species compared with species prevalent in post-treatment infection, which are well equipped to endure starvation and survive in low numbers on minimal serum. These findings point to starvation-survival capacity as a selection factor for microbial participation in post-treatment disease.


Transmission of Staphylococcus aureus from mothers to newborns.
The study objective was to define the risk factors and the route of Staphylococcus aureus transmission between mother and newborn. Women at late pregnancy were screened for nasal and vaginal S. aureus colonization. Newborns were screened for nasal, auricular, umbilical, and rectal colonization at birth and before discharge. Carrier mothers and their newborns were rescreened at 1 month. Pulse-field gel electrophoresis was used to assess strain genetic relatedness. Of the 208 women screened, 34% were colonized with S. aureus. Overall, by 72-100 hours after birth, the cumulative incidence of S. aureus acquisition was 42.6/100 newborns of carrier mothers versus 7.4/100 newborns of noncarrier mothers (adjusted risk ratio = 5.7; 95% confidence interval [CI], 2.3-13.9). The risk to acquire a maternal strain was significantly higher than nonmaternal strain (adjusted risk ratio = 1.5; 95% CI, 1.3-1.9); Newborns to carrier mothers were also at a risk to acquire nonmaternal S. aureus strains compared with newborns to noncarrier mothers (adjusted risk ratio = 2.9; 95% CI, 1.6-5.4). The cumulative incidence of S. aureus acquisition was similar among newborns delivered by cesarean versus vaginal delivery (24.5 vs. 23.0/100 cases). At 1-month follow-up, the cumulative incidence of S. aureus acquisition reached 69.7/100 newborns of carrier mothers.Genetically identical strains were isolated in 32/40 (80%) mother-newborn pairs, among these, the source of the newborn strain was a maternal nasal strain in 29/32 (90%). Newborns of carrier mothers are at risk to acquire S. aureus colonization. Most newborns of carrier mothers are colonized within the first month of life. Horizontal transmission from the mother is probably the major source for S. aureus carriage in newborns.


A novel micro drill design based on Ros-DrillⒸ.
This paper presents the development of a novel micro drill device for single living organisms. Currently, microinjection for mice and some other species is performed with the help of piezo-driven actuators with a very small amount of mercury column in the proximal end of the pipette in order to increase the success rate. However, the toxicity of mercury exhibits a risk factor both for the operator and the injected cells. Therefore, mercury-free devices have become a necessity. Here, a novel micro drill is developed based on the same principle of Ros-DrillⒸ piercing approach; piercing via rotational movements. The new drill is driven by a brushless motor, and it incorporates the micropipette holder. Both the amplitude and the frequency of rotational oscillations can be adjusted in very wide ranges. The experiments reveal that the drill is suitable for different tasks such as microinjection and biopsy of different organisms. It presents good performance in terms of success rate, ease of usage, compactness and compatibility with different manipulation systems.


E-Cigarette Dependence in Youth.
The majority of e-cigarette vaping youth use nicotine when vaping. Some then become dependent on the nicotine, which can result in subsequent health effects. There has been limited evaluation of convergent validity of e-cigarette dependence measures for use specifically in youth. The aim of this study was to investigate and validate various e-cigarette dependence measures for use in youth populations. One thousand two hundred and five Canadian youth aged 16-24 who completed a cross-sectional online survey reported vaping at least monthly and were thus included in the analysis. E-cigarette dependence was assessed using a modified Penn State Electronic Cigarette Dependence Index (PS-ECDI), the E-Cigarette Dependence Scale (EDS), a self-perceived vaping dependence question, and time to first vape after waking. Internal consistency, convergent validity, and concurrent validity of the measures were assessed. Both the PS-ECDI and the EDS exhibited a good degree of internal consistency (α = 0.8472 and 0.8405, respectively). All measures exhibited convergent validity against each other and against time to first vape upon waking (p < .001), as well as concurrent validity against vaping frequency and nicotine concentration (p < .001). The PS-ECDI was inferior to the EDS, self-perceived measure, and time from waking when predicting daily vaping frequency, but, along with the self-perceived measure, was superior to the EDS and time from waking when predicting monthly vaping. All measures exhibit convergent and concurrent validity, as well as internal consistency. Depending on the needs of the study, it would be appropriate to use any of these measures when assessing e-cigarette dependence in adolescent and young-adult populations. The PS-ECDI and the self-perceived measure are equally effective in predicting monthly vaping, but the self-perceived measure was superior in predicting daily vaping. Thus, the one-item self-perceived measure of dependence is appropriate for use and preferable to the 11-item PS-ECDI or the 4-item EDS in situations of limited time or where subjects are at risk of respondent fatigue, and is superior to time to first vape after waking to predict vaping frequency.


Flunarizine selectively blocks transient calcium channel currents in N1E-115 cells.
The sensitivities of two types of voltage-dependent calcium channel currents in N1E-115 neuroblastoma cells to various agents were studied using the whole cell version of the patch clamp technique. Cells cultured in normal media expressed predominantly transient (T) currents whereas cells cultured in media with dimethylsulfoxide for 1 month expressed predominantly long-lasting (L) currents. Furthermore, by selecting cells with one or two short neurites it was possible to obtain cells which expressed only L channels. The dihydropyridine agonist, Bay K-8644 (5 microM), increased the amplitude of L channel currents by a factor of nearly two, whereas T channel currents were unaffected. Nifedipine (0.1 mM) significantly inhibited L channel currents, whereas T channel currents were insensitive to this treatment. Flunarizine, a diphenylpiperazine, had no effect on L channel currents but selectively inhibited T channel currents in a dose-dependent manner, with a significant effect at a concentration of 1 microM. However, flunarizine did not change the I-V relationships of T channel currents. Furthermore, the voltage dependence of T channel inactivation was shifted toward more negative potential by flunarizine. The present study provides direct evidence of the selective inhibition of T channel currents by flunarizine in N1E-115 neuroblastoma cells.


Therapy-related acute myeloid leukemia with CBFB/MYH11 in a patient with ovarian cancer after exposure to chemotherapy.
In patients with acute myeloid leukemia (AML), about 25%-35% of patients have a history of other hematological diseases, 10% of patients have a history of malignant tumors in other systems and have received cytotoxic treatment including chemotherapy and/or radiation, and the disease is categorized as therapy-related acute myeloid leukemia (t-AML) according to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Two subsets of t-AML are generally recognized based on the nature of prior treatments and the characteristics of the disease. The most common type occurs after exposure to alkylating agents and/or radiation, with a latent period of 5 to 10 years. The less common type occurs after treatment with agents targeting topoisomerase II and has a shorter latent period of 1 to 5 years. The majority of these cases are associated with balanced recurrent chromosomal translocations frequently involving MLL at 11q23, RUNX1 at 21q22, or CBFB at 16q22 and morphologically resemble the features of de novo AML associated with these translocations. Here, we describe a rare case of a 48-year-old female with ovarian cancer who developed AML with CBFB/MYH11 fusion, less than two years after exposure to paclitaxel and carboplatin chemotherapy.


Influence of serum percentage on the behavior of Wharton's jelly mesenchymal stem cells in culture.
Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into several lineages with valuable applications in regenerative medicine. MSCs differentiation is highly dependent on physicochemical properties of the culture substrate, cell density and on culture medium composition. In this study, we assessed the influence of fetal bovine serum (FBS) level on Wharton's jelly (WJ)-MSCs behavior seeded on polyelectrolyte multilayer films (PEMF) made of four bilayers of poly-allylamine hydrochloride (PAH) as polycation and poly-styrene sulfonate (PSS) as polyanion. MSCs isolated from WJ by explants method were amplified until the third passage. Their phenotypic characterization was performed by flow cytometry analyses. MSCs were seeded on PEMF, in Endothelial growth medium-2 (EGM-2) supplemented by either 5% or 2% FBS. Cell's behavior was monitored for 20 days by optical microscopy and immunofluorescence. Until 2 weeks on glass slides, no difference was observed whatever the FBS percentage. Then with 5% FBS, MSCs formed three-dimensional spheroids on PSS/PAH after 20 days of culture with a nuclear aggregate. Whereas, with 2% FBS, these spheroids did not appear and cells grown in 2D conserved the fibroblast-like morphology. The decrease of FBS percentage from 5% to 2% avoids 3D cell spheroids formation on PAH/PSS. Such results could guide bioengineering towards building 2D structures like cell layers or 3D structures by increasing the osteogenic or chondrogenic differentiation potential of MSCs.


Alzheimer's Disease Caregiver Characteristics and Their Relationship with Anticipatory Grief.
In Alzheimer's disease, two fundamental aspects become important for caregivers: ambiguity and ambivalence. Thus, anticipatory grief is considered an active psychological process that is very different from the mere anticipation of death. The present study aims to determine which characteristics of family caregivers of people with dementia, such as age, gender, educational level, relationship with the person with dementia, years with dementia or years as a caregiver, are related to the presence of anticipatory grief. A cross-sectional design was employed. The sample consisted of a total of 129 subjects who cared for a family member with dementia. A sociodemographic data sheet and a battery of tests measure the presence of anticipatory grief, caregiver burden and/or psychopathology. The results obtained allowed us to confirm some of the hypotheses regarding the anticipatory grief construct, the importance of the care time factor, in years and per day, as well as the relevance of the previous demographic and psychopathological profile (being female, spouse function and possible depressive symptomatology). Likewise, from the prediction analyzes performed, it seems that these variables can predict anticipatory grief. These results propose interesting opportunities to formulate care proposals to professionals and family caregivers in relation to care tasks and caregiver skills.


Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats.
The incidence and degree of cysteamine- or dulcerozine-induced duodenal ulcers are increased by systemic capsaicin desensitization (50 mg kg-1 s.c. 4 days before) in adult rats. Acute administration of capsaicin, but not neurokinins or CGRP, produced a small but distinct plasma extravasation (Evans blue leakage) in the rat proximal duodenum which was absent in capsaicin-pretreated rats. These findings indicate the existence of a capsaicin-sensitive 'duodenal defence mechanism' in rats.


Implementing the figure of peer support workers in mental health: an international perspective from the context of its implementation in Catalonia.
In the context of debates surrounding the training of mental health peer support workers and their incorporation into the Catalan Health System, this article presents a literature review complemented by interviews carried out between 2020 and 2021 with both international and Spanish experts. Based on the information obtained, content analysis of elements of their training and integration within the health system was performed. German-speaking countries offer the most homogeneous training and recruitment programs. In the case of English- and French-speaking countries, non-profit or third sector organizations are usually in charge of training programs and recruitment. Various experiences with training programs exist in the Ibero-American world, although they are not recognized as professional qualifications. Recommendations are offered for the development of this figure in Catalonia, which include advancing towards professional training with recognition as health care providers, as well as contracting options from both socio-health or health care providers or from third sector entities.


Force illusions and drifts observed during muscle vibration.
We explored predictions of a scheme that views position and force perception as a result of measuring proprioceptive signals within a reference frame set by ongoing efferent process. In particular, this hypothesis predicts force illusions caused by muscle vibration and mediated via changes in both afferent and efferent components of kinesthesia. Healthy subjects performed accurate steady force production tasks by pressing with the four fingers of one hand (the task hand) on individual force sensors with and without visual feedback. At various times during the trials, subjects matched the perceived force using the other hand. High-frequency vibration was applied to one or both of the forearms (over the hand and finger extensors). Without visual feedback, subjects showed a drop in the task hand force, which was significantly smaller under the vibration of that forearm. Force production by the matching hand was consistently higher than that of the task hand. Vibrating one of the forearms affected the matching hand in a manner consistent with the perception of higher magnitude of force produced by the vibrated hand. The findings were consistent between the dominant and nondominant hands. The effects of vibration on both force drift and force mismatching suggest that vibration led to shifts in both signals from proprioceptors and the efferent component of perception, the referent coordinate and/or coactivation command. The observations fit the hypothesis on combined perception of kinematic-kinetic variables with little specificity of different groups of peripheral receptors that all contribute to perception of forces and coordinates. NEW & NOTEWORTHY We show that vibration of hand/finger extensors produces consistent errors in finger force perception. Without visual feedback, finger force drifted to lower values without a drift in the matching force produced by the other hand; hand extensor vibration led to smaller finger force drift. The findings fit the scheme with combined perception of kinematic-kinetic variables and suggest that vibration leads to consistent shifts of the referent coordinate and, possibly, of coactivation command to the effector.


Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia.
Exogenous progesterone has been shown to reduce brain edema and ischemia-induced cell damage and to improve physiological and neurological function during the early stage of focal cerebral ischemia. In the present study, the authors assessed the neuroprotective potential of progesterone during the late stage of ischemia in a transient middle cerebral artery (MCA) occlusion model in the rat. Forty-eight male spontaneously hypertensive rats were randomly assigned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accomplished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion volume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group. Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with control rats. Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.


Why are carbapenems active against Enterobacter cloacae resistant to third generation cephalosporins?
The broad antibacterial activity of carbapenems includes Gram-negative rods resistant to third generation cephalosporins. To increase the understanding of this improved activity, the factors involved in the efficacy of imipenem and ceftriaxone against Enterobacter cloacae have been examined. Resistance to ceftriaxone is primarily the result of a selection of resistant clones ("derepressed mutants"), pre-existing within the Enterobacter populations. Most of the resistant clones produce large amounts of beta-lactamases, and some of them show a decreased expression of porin F coupled with an increased expression of porin C. Determination of outer membrane permeability, as calculated in intact cells using a HPLC-based technique, showed that imipenem penetrated three times faster than ceftriaxone. Moreover, unlike ceftriaxone, imipenem penetration was not affected in a porin F deficient mutant. This suggests that imipenem has an additional pathway not available for ceftriaxone, possibly porin C. The rate of beta-lactamase hydrolysis in experimental conditions thought to be physiologically relevant, and the affinity for PBPs, estimated by calculation, were similar for the two antibiotics. Thus, the activity of imipenem against ceftriaxone resistant E. cloacae seems to result mainly from a selective permeability of the outer membrane.


Statistical methods for handling unwanted variation in metabolomics data.
Metabolomics experiments are inevitably subject to a component of unwanted variation, due to factors such as batch effects, long runs of samples, and confounding biological variation. Although the removal of this unwanted variation is a vital step in the analysis of metabolomics data, it is considered a gray area in which there is a recognized need to develop a better understanding of the procedures and statistical methods required to achieve statistically relevant optimal biological outcomes. In this paper, we discuss the causes of unwanted variation in metabolomics experiments, review commonly used metabolomics approaches for handling this unwanted variation, and present a statistical approach for the removal of unwanted variation to obtain normalized metabolomics data. The advantages and performance of the approach relative to several widely used metabolomics normalization approaches are illustrated through two metabolomics studies, and recommendations are provided for choosing and assessing the most suitable normalization method for a given metabolomics experiment. Software for the approach is made freely available.


The antioxidant properties of zinc.
The ability of zinc to retard oxidative processes has been recognized for many years. In general, the mechanism of antioxidation can be divided into acute and chronic effects. Chronic effects involve exposure of an organism to zinc on a long-term basis, resulting in induction of some other substance that is the ultimate antioxidant, such as the metallothioneins. Chronic zinc deprivation generally results in increased sensitivity to some oxidative stress. The acute effects involve two mechanisms: protection of protein sulfhydryls or reduction of (*)OH formation from H(2)O(2) through the antagonism of redox-active transition metals, such as iron and copper. Protection of protein sulfhydryl groups is thought to involve reduction of sulfhydryl reactivity through one of three mechanisms: (1) direct binding of zinc to the sulfhydryl, (2) steric hindrance as a result of binding to some other protein site in close proximity to the sulfhydryl group or (3) a conformational change from binding to some other site on the protein. Antagonism of redox-active, transition metal-catalyzed, site-specific reactions has led to the theory that zinc may be capable of reducing cellular injury that might have a component of site-specific oxidative damage, such as postischemic tissue damage. Zinc is capable of reducing postischemic injury to a variety of tissues and organs through a mechanism that might involve the antagonism of copper reactivity. Although the evidence for the antioxidant properties of zinc is compelling, the mechanisms are still unclear. Future research that probes these mechanisms could potentially develop new antioxidant functions and uses for zinc.


The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue.
Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs. Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters. Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement. Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.


Impact of environmental cleaning on the colonization and infection rates of multidrug-resistant Acinetobacter baumannii in patients within the intensive care unit in a tertiary hospital.
To continuously evaluate the effect of environmental cleaning and hand hygiene compliance on the colonization and infection rates of multidrug-resistant Acinetobacter baumannii (MDR-AB) in the patients within an intensive care unit (ICU). Environmental cleaning on the high-touch clinical surfaces (HTCS) within a comprehensive ICU was evaluated through monitoring fluorescent marks when the overall compliance with hand hygiene during 2013-2014 was monitored. Meanwhile, samples from the HTCS and inpatients were collected and sent for bacterial culture and identification. The drug susceptibility testing was further implemented to monitor the prevalence of MDR-AB. The genetic relatedness of MDR-AB collected either from the HTCS or inpatients was analyzed by pulsed field gel electrophoresis (PFGE) when an outbreak was doubted. The overall compliance with hand hygiene remained relatively stable during 2013-2014. Under this circumstance, the clearance rate of fluorescence marks on the environmental surfaces within ICUs significantly increased from 21.9 to 85.7%, and accordingly the colonization and infection rates of MDR-AB decreased from 16.5 to 6.6‰ and from 7.4 to 2.8‰, respectively, from the beginning to the end of 2013. However, during 2014, because of frequent change and movement of environmental services staff, the clearance rate of fluorescence marks decreased below 50.0%, and the overall colonization and infection rates of MDR-AB correspondingly increased from 9.1 to 11.1‰ and from 1.5 to 3.9‰, respectively. PFGE displayed a high genetic relatedness between the MDR-AB strains analyzed, indicating a dissemination of MDR-AB during the surveillance period. For the easily disseminated MDR-AB within ICUs, the clearance rate of fluorescence labeling on HTCS is negatively correlated with the hospital infection rate of MDR-AB. Such an invisible fluorescence labelling is an effective and convenient method to continuously monitor cleanness of medical environment within hospitals.


Compressive Estimation and Imaging Based on Autoregressive Models.
Compressed sensing (CS) is a fast and efficient way to obtain compact signal representations. Oftentimes, one wishes to extract some information from the available compressed signal. Since CS signal recovery is typically expensive from a computational point of view, it is inconvenient to first recover the signal and then extract the information. A much more effective approach consists in estimating the information directly from the signal's linear measurements. In this paper, we propose a novel framework for compressive estimation of autoregressive (AR) process parameters based on ad hoc sensing matrix construction. More in detail, we introduce a compressive least square estimator for AR(p) parameters and a specific AR(1) compressive Bayesian estimator. We exploit the proposed techniques to address two important practical problems. The first is compressive covariance estimation for Toeplitz structured covariance matrices where we tackle the problem with a novel parametric approach based on the estimated AR parameters. The second is a block-based compressive imaging system, where we introduce an algorithm that adaptively calculates the number of measurements to be acquired for each block from a set of initial measurements based on its degree of compressibility. We show that the proposed techniques outperform the state-of-the-art methods for these two problems.


TRIOLEIN-I-131 TOLERANCE IN PATIENTS WITH CORONARY HEART DISEASE.
The value of the oral triolein-I(131) "tolerance" test in the study of patients with coronary heart disease was assessed. Thirtynine patients were divided into three groups: those with clinical evidence of coronary heart disease, those with increased risk, and those with no increased risk of coronary heart disease. The variability of the results precluded differentiation between the groups on the basis of this test. A minority of the patients with coronary heart disease showed strikingly elevated blood levels of lipid-bound radioactivity following the oral ingestion of triolein-I(131). It was concluded that this test is of no use in the diagnosis of coronary heart disease but may identify those patients with coronary heart disease who dispose of orally ingested fat in a grossly abnormal fashion.


Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification.
Direct comparison of the hepatoma cell lines HepG2 and HepaRG has previously been performed by only evaluating a limited set of genes or proteins. In this study, we examined the whole-genome gene expression of both cell lines before and after exposure to the genotoxic (GTX) carcinogens aflatoxin B1 and benzo[a]pyrene and the nongenotoxic (NGTX) carcinogens cyclosporin A, 17beta-estradiol, and 2,3,7,8-tetrachlorodibenzo-para-dioxin for 12 and 48 h. Before exposure, this analysis revealed an extensive network of genes and pathways, which were regulated differentially for each cell line. The comparison of the basal gene expression between HepG2, HepaRG, primary human hepatocytes (PHH), and liver clearly showed that HepaRG resembles PHH and liver the most. After exposure to the GTX and NGTX carcinogens, for both cell lines, common pathways were found that are important in carcinogenesis, for example, cell cycle regulation and apoptosis. However, also clear differences between exposed HepG2 and HepaRG were observed, and these are related to common metabolic processes, immune response, and transcription processes. Furthermore, HepG2 performs better in discriminating between GTX and NGTX carcinogens. In conclusion, these results have shown that HepaRG is a more suited in vitro liver model for biological interpretations of the effects of exposure to chemicals, whereas HepG2 is a more promising in vitro liver model for classification studies using the toxicogenomics approach. Although, it should be noted that only five carcinogens were used in this study.


Testicular infarction complicating strangulated inguinal herniae in Nigerian children.
Between 1985 and 1990 30 children were operated on for strangulated inguinal herniae in the University of Benin Teaching Hospital, Benin City, Nigeria. Six of the children (20%) had testicular infarction secondary to the strangulated hernia. Half of the children with infarcted testes had viable bowel at operation. The surgeon dealing with African children with strangulated herniae needs to be sensitised to this condition and the possibility that the testis may well be infarcted before the intestines.


Laparoscopic myomectomy using self-made retrieval bag to contain tissue extraction.
To introduce an effective approach using a self-made retrieval bag during laparoscopic myomectomy to contain tissue extraction. Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique, approved by the Shengjing Hospital of China Medical University. University hospital. A 32-year-old woman diagnosed with a uterine myoma (diameter, 6 cm). She had endured 5 years of intermittent lower abdominal pain and 2 years of infertility. A self-made retrieval bag during laparoscopic myomectomy was used (consists of four steps) to contain tissue extraction. 1. Self-made retrieval bag using a sterile medical bag. 2. Inspect the pelvic cavity, evaluate and determine the location and number of myomas. 3. Resect the myoma. 4. Morcellate the myoma into pieces inside the retrieval bag using laparoscopic power morcellation. Value and feasibility of using a self-made retrieval bag in laparoscopic myomectomy. The myoma was successfully and completely resected by laparoscopy using a self-made retrieval bag to contain tissue extraction. Operative time was 93 minutes. In the follow-up period, the patient did not report any symptom of iatrogenic parasitic myoma. The woman had a pregnancy at month 26 after operation and underwent a cesarean section. This resulted in a full-term baby. Our surgical approach demonstrated a number of noteworthy advantages. The use of retrieval bag to contain tissue extraction during laparoscopic morcellation can avoid the risk of iatrogenic parasitic myoma. The retrieval bag is self-made using a sterile packing bag, which is cost free and also reduces operative expenses.


Culture and differentiation of purified human adipose-derived stem cells by membrane filtration via nylon mesh filters.
Human adipose-derived stem cells (hASCs) cultured for 5 passages were filtered through nylon (NY) mesh filter membranes coated with and without extracellular matrix proteins to obtain the permeation solution. Subsequently, the culture media were filtered via the membranes to obtain the recovery solution. Then, the membranes were cultured in cell culture medium to obtain the migrated cells from the membranes. The hASCs in the permeation solution, through any type of NY mesh filter membrane having 11 and 20 μm pore sizes, had lower osteogenic differentiation ability than conventional hASCs cultured on tissue culture polystyrene (TCP) dishes for passage 5, whereas the hASCs purified by the membrane migration method through NY mesh filter membranes coated with recombinant vitronectin, which have 11 and 20 μm pore sizes, showed a higher proliferation speed as well as higher osteogenic differentiation potential than the conventional hASCs cultured on TCP dishes for passage 5. The membrane filtration and migration methods would be useful for cell sorting for specific cells, such as hASCs with high proliferation and high osteogenic differentiation ability, which do not need antibody binding or genetic modification of the cells for the specific isolation of the cells.


Simulating the effects of climate change on the carbon balance of North American high-latitude forests.
The large magnitude of predicted warming at high latitudes and the potential feedback of ecosystems to atmospheric CO2 concentrations make it important to quantify both warming and its effects on high-latitude carbon balance. We analysed long-term, daily surface meteorological records for 13 sites in Alaska and north-western Canada and an 82-y record of river ice breakup date for the Tanana River in interior Alaska. We found increases in winter and spring temperature extrema for all sites, with the greatest increases in spring minimum temperature, average 0.47 °C per 10 y, and a 0.7-day per 10 y advance in ice breakup on the Tanana River. We used the climate records to drive an ecosystem process model, BIOME_BGC, to simulate the effects of climate change on the carbon and water balances of boreal forest ecosystems. The growing season has lengthened by an average of 2.6 days per 10 y with an advance in average leaf onset date of 1.10 days per 10 y. This advance in the start of the active growing season correlates positively with progressively earlier ice breakup on the Tanana River in interior Alaska. The advance in the start of the growing season resulted in a 20% increase in net primary production for both aspen (Populus tremuloides) and white spruce (Picea glauca) stands. Aspen had a greater mean increase in maintenance respiration than spruce, whereas spruce had a greater mean increase in evapotranspiration. Average decomposition rates also increased for both species. Both net primary production and decomposition are enhanced in our simulations, suggesting that productive forest types may not experience a significant shift in net carbon flux as a result of climate warming.


An affinity label for the regulatory dithiol of ribulose-5-phosphate kinase from maize (Zea mays).
Ribulose-5-phosphate kinase from maize (Zea mays) can exist in either a reduced, active form or an oxidized, inactive form. Reduced ribulose-5-phosphate kinase is rapidly and irreversibly inactivated by the dichlorotriazine dye Reactive Red 1 (Procion Red MX-2B), but the irreversible inactivation of the oxidized form of ribulose-5-phosphate kinase occurs at only 0.05% of this rate. The rate of inactivation of the reduced enzyme by Reactive Red 1 (apparent bimolecular rate constant 10(4)M-1 X s-1 at pH 7.4 and 25 degrees C) is several orders of magnitude greater than previous estimates of the rates of dye-mediated inactivation of other enzymes. The dye-dependent inactivation of the reduced enzyme is inhibited by Hg2+ or p-mercuribenzoate (thiol reagents that reversibly inhibit ribulose-5-phosphate kinase activity), or by ATP and ADP, the nucleotide substrates of the enzyme. Hydrolysed Reactive Red 1, which does not inactivate the enzyme, is a reversible inhibitor of ribulose-5-phosphate kinase. This inhibition is competitive with respect to ATP (Ki approximately 0.5 mM). The dye appears to act as an affinity label for the ATP/ADP-binding site by preferentially arylating a thiol residue generated during the reductive activation of the enzyme that is achieved by dithiothreitol or thioredoxin in vitro or during illumination of leaves.


Climate-driven sympatry may not lead to foraging competition between congeneric top-predators.
Climate-driven sympatry may lead to competition for food resources between species. Rapid warming in the West Antarctic Peninsula (WAP) is coincident with increasing gentoo penguin and decreasing Adélie penguin populations, suggesting that competition for food may exacerbate the Adélie penguin decline. On fine scales, we tested for foraging competition between these species during the chick-rearing period by comparing their foraging behaviors with the distribution of their prey, Antarctic krill. We detected krill aggregations within the horizontal and vertical foraging ranges of Adélie and gentoo penguins, and found that krill selected for habitats that balance the need to consume food and avoid predation. In overlapping Adélie and gentoo penguin foraging areas, four gentoo penguins switched foraging behavior by foraging at deeper depths, a strategy which limits competition with Adélie penguins. This suggests that climate-driven sympatry does not necessarily result in competitive exclusion of Adélie penguins by gentoo penguins. Contrary to a recent theory, which suggests that increased competition for krill is one of the major drivers of Adélie penguin population declines, we suggest that declines in Adélie penguins along the WAP are more likely due to direct and indirect climate impacts on their life histories.


Neuropathic pain in osteoarthritis: a review of pathophysiological mechanisms and implications for treatment.
Osteoarthritis (OA) is the leading cause of musculoskeletal pain and functional disability worldwide, affecting a growing number of individuals in the western society. Despite various conservative and interventional treatment approaches, the overall management of the condition is problematic, and pain-the major clinical problem of the disease-remains sub-optimally controlled. The objectives of this review are to present the pathophysiologic mechanisms underlying the complexity of pain in OA and to discuss the challenges for new treatment strategies aiming to translate experimental findings into daily clinical practice. A narrative literature review of studies investigating the existence of a neuropathic component in OA pain was conducted. We searched PubMed, Embase and Scopus for English language publications. A hand-search of reference lists of relevant studies was also performed. Recent advances have shed additional light on the pathophysiology of osteoarthritic pain, highlighting the contribution of central pain pathways together with the sensitisation of peripheral joint receptors and changes of the nociceptive process induced by local joint inflammation and structural bone tissue changes. Thus, a neuropathic pain component may be predominant in individuals with minor joint changes but with high levels of pain refractory to analgesic treatment, providing an alternative explanation for osteoarthritic pain perception. A growing amount of evidence suggests that the pain in OA has a neuropathic component in some patients. The deeper understanding of multiple mechanisms of OA pain has led to the use of centrally acting medicines that may have a benefit on alleviating osteoarthritic pain. The ineffective pain management and the increasing rates of disability associated with OA mandate for change in our treatment paradigm.


Recurrence phenotypes and establishment of latency following rabbit keratitis produced by multiple herpes simplex virus strains.
Distinct high frequency recurrence (HFRc) or low frequency recurrence (LFRc) phenotypes were observed following rabbit keratitis with three type 1 and five type 2 herpes simplex virus strains. LFRc strains were found to have latently infected the animal but were detected very rarely, if at all, in the eye following the acute phase. The recurrence phenotypes defined in singly infected animals remained unchanged following bilateral infection of the same animal with strains of opposite phenotype. Cocultivation of virus from bilaterally infected animals showed that both virus strains were capable of latently infecting the same animal. Restriction enzyme analysis of plaque-purified virus revealed that some ganglia were latently infected with both parental strains. Recombinants were also found. Some latently infected animals could be re-infected acutely. However, establishment of latency by the superinfecting strain was inhibited.


Assignment of the casein kinase II gene family to cattle chromosomes.
Theileriosis, or East Coast fever, a parasitic disease in cattle, is associated with overexpression of casein kinase II. Casein kinase II is composed of two catalytic subunits (alpha or alpha') and two regulatory beta subunits. The genes encoding these subunits of casein kinase II were mapped to bovine chromosomes by polymerase chain reaction analysis of a well-characterized bovine x rodent somatic hybrid cell panel. The alpha-subunit (CSNK2A1) was mapped to bovine chromosome 13, the alpha'-subunit (CSNK2A2) to chromosome 5 and the beta-subunit (CSNK2B) to chromosome 23. Both CSNK2A1 and CSNK2B mapped to known regions of conserved synteny between human and cattle, while CSNK2A2 defined a new homology segment between the human and bovine genomes.


Ontogeny of osteonectin expression in embryos and larvae of sea bream (Sparus auratus).
Osteonectin (OSN) is a glycoprotein which is implicated in development, bone formation and mineralisation, tumorigenesis, angiogenesis, and wound healing. Regulation of its expression by hormones may be one of the mechanisms by which the endocrine system affects bone metabolism. As a first step to understanding OSN function in fish, the gene expression of the recently cloned cDNA for sea bream, Sparus auratus, osteonectin (sbOSN) was characterised during embryonic and larval development. sbOSN mRNA was first detected by semi-quantitative reverse transcription-polymerase chain reaction in embryos at early gastrula and its expression increased continuously until hatch, after which it decreased until 15 days post-hatch (dph), increased transiently until 24 dph and decreased thereafter. In situ hybridisation showed it had a differential tissue distribution which was age dependent. In general, sbOSN mRNA was identified in cartilaginous and calcified structures of both dermal and endochondral origin but its expression was not restricted to the skeleton. sbOSN transcripts were also detected in the skin, perichordal sheath, nerve cord, and kidney tubules.


[Effects of maize plant type and planting width on the early morphological characters and yield of relayplanted soybean].
This paper studied the effects of different maize plant type and planting width on the early morphological characters and yield of relayplanted soybean under wheat/maize/soybean relayplanting. The results showed that different maize plant type led to different micro-climate in soybean planting strip, which was a direct factor affecting the changes in morphological characters and tissue structure of soybean. Large planting width and relay cropping with erect maize resulted in the short plant, thick main stem, large accumulation of dry matter, higher LAI and SLM, and high yield of soybean, while small planting width and relay cropping with flat maize led to the undergrowth of leaf and stem, overgrowth of plant, thin and lodging-susceptible stem, and low yield of soybean. From the tissue sections of soybean leaf and stem at early blossoming stage under conditions of planted with different maize plant type and 1.17 m/0.83 m (soybean/maize) of planting width, it was found that under more shading, the leaf thickness decreased, epidermis cells became larger, cuticle became thinner, differentiation of palisade tissue and spongy tissue was inconspicuous, space between cells was large, epidermis and secondary xylem of stem all became thinner, parenchyma cells were loose, formulation of vessel delayed, and phloem fibers were less developed. It was concluded that relayplanting soybean with erect maize in a planting width of 1.17 m/0.83 m (soybean/maize) could be the best field combination in ensuring high yield and high efficiency all the year round.


Analysis of respiration during germination and enlargement of spores of Bacillus megaterium and of the fungus Myrothecium verrucaria.
1. There are certainly two, and probably three, stages in the development of B. megaterium from the spore to inception of cell division. The rapid increase in rate of respiration during the initial 10 minutes on glucose-peptone-yeast extract medium coincides with decrease in optical density and with increase in stainability. From about 10 to 100 minutes, the rate increases linearly, coinciding with swelling of the spores and ending at approximately the time of rupture of the spore case. From about 100 to 180 minutes, there is a second and steeper linear increase in respiration rate coinciding with cell elongation. These physiological and morphological phenomena are discussed as criteria for germination. 2. The rate of respiration of M. verrucaria spores also increases linearly up to about 300 minutes in sucrose-yeast extract medium. No breaks in the curves are observed during formation of the germ tubes. 3. Oxygen uptake follows the parabolic curve See PDF for Equation within the limits of experimental error for both types of spores. 4. It is postulated that metabolism during these stages of linear increase may be regulated by processes occurring at cellular or intracellular surfaces or by synthesis of a limiting enzyme at constant rate.


Expression profile of differentially-regulated genes during progression of androgen-independent growth in human prostate cancer cells.
Because of the heterogeneous nature of prostate cancer, identifying the molecular mechanisms involved during the transition from an androgen-sensitive to an androgen-independent phenotype is very complex. An LNCaP cell model that recapitulates prostate cancer progression, comprising early passage androgen-sensitive (LNCaP-C33) and late passage androgen-independent (LNCaP-C81) phenotypes, would help to provide a better understanding of such molecular events. In this study, we examined the genes expressed by LNCaP-C33 and LNCaP-C81 cells using cDNA microarrays containing 1176 known genes. This analysis demonstrated that 34 genes are up-regulated and eight genes are down-regulated in androgen-independent cells. Northern blot analysis confirmed the differences identified by microarrays on several candidate genes, including c-MYC, c-MYC purine-binding transcription factor (PuF), macrophage migration inhibitory factor (MIF), macrophage inhibitory cytokine-1 (MIC-1), lactate dehydrogenase-A (LDH-A), guanine nucleotide-binding protein Gi, alpha-1 subunit (NBP), cyclin dependent kinase-2 (CDK-2), prostate-specific membrane antigen (PSM), cyclin H (CCNH), 60S ribosomal protein L10 (RPL10), 60S ribosomal protein L32 (RPL32), and 40S ribosomal protein S16 (RPS16). These differentially-regulated genes are correlated with progression of human prostate cancer and may be of therapeutic relevance as well as an aid in understanding the molecular genetic events involved in the development of this disease's hormone-refractory behavior.


Modifying effect of dietary fat on benzo[a]pyrene-induced respiratory tract tumours in hamsters.
Groups of 40 Syrian golden hamsters of both sexes were fed diets containing either 5% fat (control), 20% saturated fat (beef tallow) or 20% unsaturated fat (sunflower seed oil) from weaning and during the whole experimental period (up to 656 days). Respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene attached to ferric oxide and suspended in saline. Mortality was slightly, but not statistically significantly higher in the high fat groups than in the low fat control group. Microscopic examination of the respiratory tract revealed an increased number of tumour bearing animals, an increased multiplicity of respiratory tract tumours and an increased total number of respiratory tract tumours in animals fed high fat diets. The tumour enhancing effect of fat was most pronounced in the high unsaturated fat group. Especially epidermoid papillomas, epidermoid carcinomas and combined epidermoid and adenocarcinomas contributed to the observed differences in tumour response amongst groups. It was concluded that dietary fat enhances benzo[a]pyrene-induced respiratory tract carcinogenesis in hamsters.


A mathematical framework for minimally invasive tumor ablation therapies.
Minimally invasive tumor ablations (MITAs) are an increasingly important tool in the treatment of solid tumors across multiple organs. The problems experienced in modeling different types of MITAs are very similar, but the development of mathematical models is mostly performed in isolation according to modality. Fundamental research into the modeling of specific types of MITAs is indeed required, but to choose the optimal treatment for an individual the primary clinical requirement is to have reliable predictions for a range of MITAs. In this review of the mathematical modeling of MITAs 4 modalities are considered: radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. The similarities in the mathematical modeling of these treatments are highlighted, and the analysis of the models within a general framework is discussed. This will aid in developing a deeper understanding of the sensitivity of MITA models to physiological parameters and the impact of uncertainty on predictions of the ablation zone. Through robust validation and analysis of the models it will be possible to choose the best model for a given application. This is important because many different models exist with no objective comparison of their performance. The collection of relevant in vivo experimental data is also critical to parameterize such models accurately. This approach will be necessary to translate the field into clinical practice.


Is the strength of implicit alcohol associations correlated with alcohol-induced heart-rate acceleration?
Heart rate (HR) acceleration during the ascending limb of the blood alcohol curve has proven to be a reliable measure of the sensitivity to the activating effects of alcohol. In this study, we investigated the correlation between an ethanol-induced cardiac change and the strength of implicit alcohol-related arousal and approach associations and attentional bias for alcohol-related stimuli in heavy drinkers. These 3 types of implicit alcohol-related cognitions have been proposed to reflect the strength of incentive sensitization that is experienced after repeated alcohol use. Forty-eight heavy drinking men performed a modified version of the Implicit Association Test (IAT) to measure their implicit alcohol arousal and approach-avoidance associations. A modified version of the emotional Stroop was used to measure attentional bias for alcohol-related stimuli (blocked and unblocked). Next, a high dose of alcohol (1.0 mL/kg body weight 95% USP alcohol) was administered in a short period of time. Resting baseline HR, blood alcohol concentrations, mood, and craving for alcohol were assessed before alcohol administration and for 2 hours post-alcohol consumption. Contrary to our hypothesis, a negative association was found between implicit arousal associations and alcohol-induced HR change. This indicates that strong arousal associations were correlated with a decrease in alcohol-induced HR. Approach associations and attentional bias were not correlated with alcohol-induced HR change, but both were correlated positively with each other. Alcohol-arousal associations and other implicit cognitions (attentional bias, approach associations) are not positively related to individual differences in the sensitivity to alcohol's activating effects, at least not in the present sample consisting primarily of family history-negative heavy drinkers.


Cognitive behavioral therapy-based brief intervention for volatile substance misusers during adolescence: a follow-up study.
Of 62 males admitted for treatment in Turkey in 2008 with a diagnosis of volatile substance misuse (VSM) dependency, half were randomly allocated to receive a cognitive behavioral therapy (CBT)-based brief intervention and an education program and half participated only in the education program. One year after treatment, 38.2% of the experimental group and 58.1% of the control group had continued VSM during the last three months. This statistically significant difference indicates that CBT-based brief intervention is associated with reducing VSM in adolescents. Factors associated with abstinence after treatment are identified and study limitations are noted.


Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors.
GRP78 is a stress-inducible chaperone protein with antiapoptotic properties that is overexpressed in transformed cells and cells under glucose starvation, acidosis, and hypoxic conditions that persist in poorly vascularized tumors. Previously we demonstrated that the Grp78 promoter is able to eradicate tumors using murine cells in immunocompetent models by driving expression of the HSV-tk suicide gene. Here, through the use of positron emission tomography (PET) imaging, we provide direct evidence of spontaneous in vivo activation of the HSV-tk suicide gene driven by the Grp78 promoter in growing tumors and its activation by photodynamic therapy (PDT) in a controlled manner. In this report, we evaluated whether this promoter can be applied to human cancer therapy. We observed that the Grp78 promoter, in the context of a retroviral vector, was highly activated by stress and PDT in three different types of human breast carcinomas independent of estrogen receptor and p53. Complete regression of sizable human tumors was observed after prodrug ganciclovir treatment of the xenografts in immunodeficient mice. In addition, the Grp78 promoter-driven suicide gene is strongly expressed in a variety of human tumors, including human osteosarcoma. In contrast, the activity of the murine leukemia virus (MuLV) long-terminal repeat (LTR) promoter varied greatly in different human breast carcinoma cell lines, and in some cases, stress resulted in partial suppression of the LTR promoter activity. In transgenic mouse models, the Grp78 promoter-driven transgene is largely quiescent in major adult organs but highly active in cancer cells and cancer-associated macrophages, which can diffuse to tumor necrotic sites devoid of vascular supply and facilitate cell-based therapy. Thus, transcriptional control through the use of the Grp78 promoter offers multiple novel approaches for human cancer gene therapy.


Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0.
Herpes simplex virus type 1 is capable of inhibiting host cell DNA synthesis following lytic infection. However, the mechanism and nature of potential effects on cell cycle progression have not been described. In this report, we characterize the dysregulation of the cell cycle following infection with the replication-incompetent virus d106, where immediate-early gene expression is restricted to infected-cell polypeptide 0 (ICP0) and the expression of all other viral genes is dramatically reduced or is not observed. Infection with d106 resulted in the accumulation of cells in both the G(1)/S and G(2)/M compartments, consistent with cell cycle arrest at both checkpoints. The isogenic variant d109, which does not express any viral proteins, failed to induce this phenotype, suggesting that the expression of ICP0 is crucial for cell cycle arrest. Analysis of global cellular gene expression patterns following infection with d106 and d109 revealed that a relatively small subset of cellular genes were induced as a consequence of ICP0 expression. A number of these genes induced in the presence of ICP0 are classically considered p53-responsive genes, including p21, gadd45, and mdm-2. However, infection with d106 of cells with both alleles of p53 deleted resulted in the same cell cycle arrest phenotype and similar cellular gene expression patterns, suggesting that the expression of ICP0 results in cell cycle arrest potentially via p53-dependent and p53-independent mechanisms. In addition, it was found that the effects of infection with d106 on viral and cellular gene expression were similar to the effects observed following treatment of cells with the histone deacetylase inhibitor trichostatin A.


Low-profile versus standard-profile multibranched thoracoabdominal aortic stent grafts.
This study compared midterm results using low-profile stent grafts (LPSGs; 18F) and standard-profile stent grafts (SPSGs; 22F-24F) for endovascular pararenal and thoracoabdominal aortic aneurysm (TAAA) repair. From July 2005 to March 2015, 134 asymptomatic patients underwent endovascular repair of a pararenal or TAAA using multibranched aortic stent grafts. In March 2011, we started using a LPSG with nitinol stents and thin-walled polyester fabric. Prospectively collected data on operative repair, complications, and outcomes were compared between the two groups. LPSGs were used in 37 patients (8 women [21.6%]; mean ± standard deviation age, 72.5 ± 8 years) and SPSGs in 97 patients (25 [26%] women; mean age, 73 ± 8 years). Medical comorbidities, aneurysm size, and aneurysm extent were similar in the LPSG and SPSG groups. Mean follow-up time was longer in the SPSG group (3.1 ± 2 years) than in the LPSG group (1.3 ± 0.9 years; P < .001). Operative time, renal failure, stroke, myocardial infarction, and perioperative death were not significantly different between the two groups (P > .05). Aneurysm-related death, rupture, stent graft migration, type I or III endoleaks, aneurysm enlargement >5 mm, branch vessel occlusion, and reintervention rates were similar between the two groups (P > .05). However, the combined outcome of conduit use or access artery injury occurred at a lower rate in the LPSG group than in the SPSG group (16% vs 36%; P = .03). Women experienced significantly higher rates of conduit use and access artery injury than men after repair with SPSGs (64% vs 26%, respectively; P = .001) but similar rates after repair with the LPSG (25% vs 14%, respectively; P = .45). LPSGs had similar safety profile and midterm outcomes compared with the SPSGs for treatment of pararenal and TAAA. The substitution of LPSGs for SPSGs lowered the number of patients who required conduit insertion to avoid access artery injury, especially in women, thereby reducing an otherwise striking gender difference.


Nitrogen removal from reject water with primary sludge as denitrification carbon source.
A novel system was used for nitrogen removal from reject water. This system includes one anoxic/oxic reactor for nitrification and a special reactor for denitrification in which primary sludge was added intermittently as electron donor. In denitrification reactor, sludge fermentation and denitrification reaction took place simultaneously and promoted each other. It was found that effluent recycle could improve nitrogen removal efficiency due to reclaiming of alkalinity. Under steady state conditions, the average solid retention time (SRT) in denitrification reactor was 12-15 d, a total nitrogen loading rate was 0.2 kg N/(m(3) day) and TN removal efficiency was more than 90% without extra carbon source addition. Primary sludge was degraded so that volatile suspended solid (VSS) decreased by 50%. Further investigation showed that ORP could be taken as a control parameter for sludge addition.


[The coiled bodies and satellite microbodies of the oocyte nuclei in hibernating Rana temporaria frogs contain actin].
Immunocytochemical analysis of preparation of dispersed nuclei content in oocytes of III-IV stages of oogenesis, in terms of Dumont (1972), from hibernating grass frogs using monoclonal antibodies against actin, revealed two types of intranuclear structures containing this protein: coiled bodies (CB) and satellite microbodies (SM). Staining of these preparations with Rhodamin-phalloidin, known specifically to interact with fibrillar actin, did not reveal it in these structures. Results of our biochemical studies, using protease ESP32 specifically cutting only globular actin, are suggesting that both CB and SM contain globular actin. Gall et al. (1975) proposed that CB may be involved in assembling and sorting of small nuclear RNA for the three main RNA processing pathways: pre-mRNA splicing, pre-rRNA processing, and histone pre-mRNA 3'-end formation. Our finding of actin in CB allows a suggestion on actin involvement in the transport of RNA processing complexes from CB to some actual places where processing of RNA takes place. According to our previous data (Tsvetkov, Parfenov., 1994), SM participate in the karyosphere capsule formation. This process is preceded by SM fusion triggered presumably by actin.


Delayed-Onset Familial Sagittal Suture Synostosis.
Sagittal craniosynostosis is the most common of all craniosynostoses. Patients with sagittal craniosynostosis exhibit a typical cranial appearance, including scaphocephaly, and an elongated head, with a fused and ridged sagittal suture. Moreover, some recent reports described atypical sagittal craniosynostosis accompanied by autism, speech delay, and hyperactivity. This condition, known as delayed-onset craniosynostosis, is rarely reported, given that it is difficult to determine if the condition is congenital or has a delayed-onset.This report describes the clinical course and treatment of 2 brothers with atypical sagittal synostosis. The shapes of their heads were not indicative of scaphocephaly and the younger brother exhibited delayed-onset sagittal synostosis. Their father and paternal grandmother exhibited similar cranial morphologies. Therefore, we hypothesized the involvement of a familial factor in the etiology of atypical sagittal synostosis in these patients.


F-domain valency determines outcome of signaling through the angiopoietin pathway.
Angiopoietin 1 and 2 (Ang1 and Ang2) modulate angiogenesis and vascular homeostasis through engagement of their very similar F-domain modules with the Tie2 receptor tyrosine kinase on endothelial cells. Despite this similarity in the underlying receptor binding interaction, the two angiopoietins have opposite effects: Ang1 induces phosphorylation of protein kinase B (AKT), strengthens cell-cell junctions and enhances endothelial cell survival while Ang2 antagonizes these effects 1-4 . To investigate the molecular basis for the opposing effects, we examined the protein kinase activation and morphological phenotypes produced by a series of computationally designed protein scaffolds presenting the Ang1 F-domain in a wide range of valencies and geometries. We find two broad phenotypic classes distinguished by the number of presented F-domains: scaffolds presenting 4 F-domains have Ang2 like activity, upregulating pFAK and pERK but not pAKT, and failing to induce cell migration and tube formation, while scaffolds presenting 6 or more F-domains have Ang1 like activity, upregulating pAKT and inducing migration and tube formation. The scaffolds with 8 or more F-domains display superagonist activity, producing stronger phenotypes at lower concentrations than Ang1. When examined in vivo , superagonist icosahedral self-assembling nanoparticles caused significant revascularization in hemorrhagic brains after a controlled cortical impact injury.


Assumptions about culture in discourse on ethnic minority health.
This paper is interested in the way the concept of culture is deployed in documents aimed at investigating, informing on and promoting aspects of ethnic minority health. Within a health-political discourse focusing increasingly on individual lifestyles, ethnic minority health became subject to increased political and professional interest in the last decades of the twentieth and the first decade of the twenty-first century. Analysis of the discourse on ethnic minority health emerging in five texts addressing health professionals shows that the culture of ethnic minority citizens is primarily seen as contributing to low levels of knowledge about health and to adverse health behavior. Thus, the texts present cultural beliefs and practices as contributing to the high prevalence of lifestyle diseases among ethnic minority population groups. The analysis, however, demonstrates that a more nuanced discourse is evolving, taking the complexity of the culture concept into account. In accordance with Danish health-political priorities, the most recent text analyzed in this study promotes an individualistic approach to both ethnic minority and Danish ethnic majority citizens.


Use of a formalin-treated, live Escherichia coli vaccine in the prevention of neonatal enteric colibacillosis in swine.
A field trial was conducted to evaluate the effectiveness of an Escherichia coli vaccine in prevention of neonatal enteric colibacillosis in swine. Sows (272 total) were allotted to control (151 sows) and vaccinated groups (121 sows). Sows in the vaccinated groups were given a single intramuscular injection of a formalin-treated, live E coli vaccine 10 to 20 days prior to farrowing. The effects of the vaccination were to: (1) reduce mortality from 2.14 to 0.93 (P less than 0.001) pigs per litter; (2) reduce number of pigs with diarrhea, from 7.28 to 3.12 (P less than 0.004) per litter; and (3) increase number of pigs weaned, from 7.62 to 8.2 (P less than 0.005) per litter. The advantages of vaccination were most apparent in the barns with less than adequate sanitation and ventilation.


Examining the role of neuroinflammation in major depression.
Recent findings have established a connection between inflammation and major depression and specifically the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. This article reviews clinical and experimental studies examining the role of the HPA axis, HPA hyperactivity (resulting in increased cortisol levels), as well as the proinflammatory cytokines tumor necrosis factor, C-reactive protein, and the interleukins, in depressed patients. Similarly this paper will review data supporting increased cytokine levels in depression and specifically differential effects in treatment-resistant patients, as well as potentially distinguishing in particular depression subtypes. Understanding the role of the immune system and inflammation in patients with major depression is essential in order to develop efficacious treatments potentially targeting inflammation in relation to the depression in order to reduce patient symptomatology and comorbidities.


Time reversal of noise sources in a reverberation room.
Usually, time reversal is studied with pulsed emissions. Here, the properties of time reversal of the acoustic field emitted by noise sources in a reverberation room are studied numerically, theoretically, and experimentally. A time domain numerical simulation of a two-dimensional enclosure shows that the intensity of a time-reversed noise is strongly enhanced right on the initial source position. A theory based on the link that exists between time reversal of noise and the "well-known" time reversal of short pulse is developed. One infers that the focal spot size equals half a wavelength and the signal to noise ratio only depends on the number of transceivers in the time reversal mirror. This last property is characteristic of the time reversal of noise. Experimental results are obtained in a 5 X 3 X 3 m3 reverberation room. The working frequency range varies from 300 Hz to 2 kHz. The ability of the time reversal process to physically reconstruct the image of two noise sources is studied. To this end, care is given to the technique to separate two close random sources, and also to the influence of temperature fluctuations on the focusing quality.