Preparation and characterization of silver nanoparticles-loaded calcium alginate beads embedded in gelatin scaffolds.
Silver nanoparticles (AgNPs)-loaded alginate beads embedded in gelatin scaffolds were successfully prepared. The AgNPs-loaded calcium alginate beads were prepared by electrospraying method. The effect of alginate concentration and applied voltage on shape and diameter of beads was studied. The diameter of dry AgNPs-loaded calcium alignate beads at various concentrations of AgNO3 ranged between 154 and 171 μm. The AgNPs-loaded calcium alginate beads embedded in gelatin scaffolds were fabricated by freeze-drying method. The water swelling and weight loss behaviors of the AgNPs-loaded alginate beads embedded in gelatin scaffolds increased with an increase in the submersion time. Moreover, the genipin-cross-linked gelatin scaffolds were proven to be nontoxic to normal human dermal fibroblasts, suggesting their potential uses as wound dressings.


Experimental studies on the pathogensis of temporal lobe epilepsy.
In 12 rhesus monkeys the injection of alumina cream into the temporal cortex, amygdala or hippocampus induced seizures after a latent period of six weeks to three months. Clinically the attacks are characterized by an arrest of movement, staring, unresponsiveness to most stimuli, wandering conjugate eye movements, automatisms, twitching of the contraleteral ear and less commonly commonly vocalization, chewing, hiccoughing, vomiting, adversive head movements and twitching of the face. The spiking from the amygdala and hippocampus, which usually fire together, propagates to the temporal cortex and multiple subcortical structures including the hypothalamus, anterior perforated space, anteromedial thalamus, cingulate gyrus, putamen, globus pallidus, subthalamus and mesencephalic reticular formation; from the temporal cortex to the amygdala and hippocampus, and secondarily to the diencephalic centers. There is a fairly consistent sequence of preferential propagation. Although there are some differences in the occurrences of clinical manifestations depending upon the sites of the focus, no specific structural correlation with clinical manifestations could be established. This experimental condition may provide a proper model for the study of clinical psychomotor epilipsy.


A high protein low fat meal does not influence glucose and insulin responses in obese individuals with or without type 2 diabetes.
When substituted for carbohydrate in a meal, dietary protein enhances glycaemic control in subjects with type 2 diabetes (DM2). It is unknown whether the effect is a result of increased protein or reduced carbohydrate. The present study aimed to compare the effects of two meals differing in protein to fat ratios on post-prandial glucose and insulin responses. This was a crossover, blind study in which obese subjects with (n = 23) and without (n = 26) DM2 consumed two meals in random order with equal amounts of energy (3.1 MJ, 741 kcal), fibre and carbohydrates and a 1-week washout period. Meals were a high protein, low fat (30% protein, 51% carbohydrates, 19% fat) meal and a low protein, high fat (15% protein, 51% carbohydrates, 34% fat) meal. Subjects were matched for age and body mass index. Plasma glucose and insulin were measured at fasting, 30, 60, 90, 120 min post-prandially. Insulin resistance and insulin sensitivity were assessed. There was no significant meal effect on glucose and insulin responses within groups. Glucose response was higher in diabetic (120 min 11 +/- 0.7 mmol L(-1)) compared to nondiabetic (120 min 5 +/- 0.2; P < 0.001) subjects. Diabetic subjects had significantly higher insulin resistance (P < 0.001) and lower insulin sensitivity (P < 0.001) than nondiabetics. Although peak insulin levels, 60 min post-prandially, did not differ between groups (81 +/- 9 pmol L(-1) for diabetic versus 79 +/- 7 pmol L(-1) for nondiabetic subjects), they were achieved much later, 90 min post-prandially, in diabetic, (99 +/- 8 pmol L(-1)) compared to nondiabetic (63 +/- 7 pmol L(-1), P = 0.002) subjects. Manipulating protein to fat ratio in meals does not affect post-prandial plasma blood glucose or insulin responses in obese people with and without DM2.


Patient engagement and reported outcomes in surgical recovery: effectiveness of an e-health platform.
Electronic health information platforms have the potential to support standardized care delivery models, engage patients, and deliver patient self-assessment tools. We tested whether an e-health platform could support the delivery and acquisition of patient-reported outcomes (PROs) during hospitalization after cardiac surgery. Secondarily, we tested if patient reported data were predictive of resource use (length of stay) or outcomes (discharge disposition). Subjects were 149 cardiac surgical patients, over age 50 years, undergoing routine surgery, with an expected length of stay of 5 to 7 days. While hospitalized, patients were provided with iPads (Apple), which delivered a personalized care plan. That plan included daily patient "To Do" lists with self-assessment modules that included recovery-related patient reported outcomes. Those included an early screen for discharge planning (ESDP) as well as daily pain and mobility self-assessments using the visual analog pain scale and the I-MOVE mobility scale. We measured completion rates for the self assessments, determined length of stay (short, intermediate, or long) and discharge disposition (home independently or other), and evaluated whether patient self-assessments were predictive of these outcomes. Patients completed 98% of the 1,418 self-assessments that were delivered. The ESDP and mobility self-assessments were predictive of length of hospital stay (p = 0.004 and p = 0.012, respectively) and of discharge disposition (p < 0.0001 and p < 0.007, respectively). Lower ESDP scores and higher I-MOVE scores were predictive of shorter lengths of stay and a higher likelihood of discharge to home independently. Our trial demonstrated that an e-health platform, combined with mobile computing, can effectively deliver customized care plans with which patients can interact. Furthermore, patient self-reported data are predictive of length of stay and discharge disposition.


Ganoderic Acid A Targeting β-Catenin in Wnt Signaling Pathway: In Silico and In Vitro Study.
Wnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation of β-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of β-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrödinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of β-catenin and ganoderic acid A with GScore (-9.44), kcal/mol, lipophilic EvdW (-2.86), electro (-0.72), Glide emodel (-50.401), MM-GBSA (-87.441), H bond (-1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner.


Chimerism and tolerance in transplantation.
Studies in experimental models (1953-1956) demonstrated that acquired donor-specific allotolerance in immunologically immature or irradiated animals is strongly associated with donor leukocyte chimerism. Bone marrow transplantation in immune-deficient or cytoablated human recipients was a logical extension (1968). In contrast, clinical (1959) and then experimental organ transplantation was systematically accomplished in the apparent absence of leukocyte chimerism. Consequently, it was assumed for many years that success with organ and bone marrow transplantation involved fundamentally different mechanisms. With the discovery in 1992 of small numbers of donor leukocytes in the tissues or blood of long-surviving organ recipients (microchimerism), we concluded that organ engraftment was a form of leukocyte chimerism-dependent partial tolerance. In this initially controversial paradigm, alloengraftment after both kinds of transplantation is the product of a double immune reaction in which responses, each to the other, of coexisting donor and recipient immune systems results in variable reciprocal clonal exhaustion, followed by peripheral clonal deletion. It was proposed with Rolf Zinkernagel that the individual alloresponses are the equivalent of the MHC-restricted T cell recognition of, and host response to, intracellular parasites and that the mechanisms of immune responsiveness, or nonresponsiveness, are governed by the migration and localization of the respective antigens. Elucidation of the mechanisms of nonresponsiveness (clonal exhaustion-deletion and immune ignorance) and their regulation removed much of the historical mystique of transplantation. The insight was then applied to improve the timing and dosage of immunosuppression of current human transplant recipients.


[Speech-language pathology formation in the city of Salvador and the consolidation of SUS].
The Human Resources in Health (HRH) academic field is recognized as a critical area, which is part of the reorientation process in the health sector. The elaboration of the Unified Health System (SUS) represents challenges to the academic field process, especially regarding new careers such as speech-language pathology. This is related with the lack of awareness regarding collective health and the past history that strengthened the public health policies in Brazil. Yet, the powerful influence of the service model to the spontaneous demand and reabilitation therapy plays another key role in the aspect. The aim was to analyze the academic field of the speech-language pathology profile in the city of Salvador, Bahia State. Documental analysis and coordinator interviews were used to investigate how the public area is characterized in 3 modules. It was noticed little adhesion of the upper level institutions to the legislation of the field; lack of contact between graduating students and collective health, and a teaching-service disconnection. The graduation of the speech therapist was shown incipient regarding SUS's consolidation. Identifying challenges and opportunities of changes in HRH formation in upper level institutions may lead to better levels of aid to the population, quality of education and expansion of theoretical and practical models of knowledge.


Living through a volcanic eruption: Understanding the experience of survivors as a phenomenological existential phenomenon.
Mount Merapi in Indonesia is the most active volcano in the world with its 4-6-year eruption cycle. The mountain and surrounding areas are populated by hundreds of thousands of people who live near the volcano despite the danger posed to their wellbeing. The aim of this study was to explore the lived experience of people who survived the most recent eruption of Mount Merapi, which took place in 2010. Investigators conducted interviews with 20 participants to generate textual data that were coded and themed. Three themes linked to the phenomenological existential experience (temporality and relationality) of living through a volcanic eruption emerged from the data. These themes were: connectivity, disconnection and reconnection. Results indicate that the close relationship individuals have with Mount Merapi and others in their neighbourhood outweighs the risk of living in the shadow of an active volcano. This is the first study to analyze the phenomenological existential elements of living through a volcanic eruption.


Cellular iron depletion and the mechanisms involved in the iron-dependent regulation of the growth arrest and DNA damage family of genes.
Iron plays a crucial part in proliferation while iron deficiency results in G(1)/S arrest, DNA damage, and apoptosis. However, the precise role of iron in cell cycle control remains unclear. We showed that iron depletion using the iron chelators, desferrioxamine (DFO), or 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311), increased the mRNA levels of the growth arrest and DNA damage 45α gene, GADD45α (Darnell, G. and Richardson, D. R. (1999) Blood 94, 781-792). In this study, we examined the effect of iron depletion on up-regulating GADD family members involved in growth control, including cell cycle arrest, apoptosis, and DNA repair, making them therapeutic targets for tumor suppression. We showed the GADD family members were up-regulated by cellular iron depletion. Further, up-regulation of GADD45α after iron deprivation was independent of hypoxia-inducible factor-1α (HIF-1α), octamer-1 (Oct-1), p53 and early growth response 1 (Egr1). We then analyzed the regulatory elements responsible for iron depletion-mediated regulation of GADD45α and identified the specific transcription factor/s involved. This region was within -117 bp and -81 bp relative to the start codon where the consensus sequences of three transcription factors are located: the CCAAT-binding factor/nuclear factor-Y (NF-Y), the stabilizing molecule v-MYB and the enhancer, CCAAT enhancer-binding protein (CEBPα). Mutation analysis, shRNA studies, Western blotting, and electrophoretic mobility shift assays led to the identification of NF-Y in the transcriptional up-regulation of GADD45α after iron depletion. Furthermore, like GADD45α, NF-YA was up-regulated after iron chelation and down-regulated by iron supplementation. These results are important for understanding the mechanisms of iron depletion-mediated cell cycle arrest, DNA damage repair, and apoptosis.


Acute care models for older people living with frailty: a systematic review and taxonomy.
The need to improve the acute care pathway to meet the care needs of older people living with frailty is a strategic priority for many healthcare systems. The optimal care model for this patient group is unclear. A systematic review was conducted to derive a taxonomy of acute care models for older people with acute medical illness and describe the outcomes used to assess their effectiveness. Care models providing time-limited episodes of care (up to 14 days) within 48 h of presentation to patients over the age of 65 with acute medical illness were included. Care models based in hospital and community settings were eligible. Searches were undertaken in Medline, Embase, CINAHL and Cochrane databases. Interventions were described and classified in detail using a modified version of the TIDIeR checklist for complex interventions. Outcomes were described and classified using the Core Outcome Measures in Effectiveness Trials (COMET) taxonomy. Risk of bias was assessed using RoB2 and ROBINS-I. The inclusion criteria were met by 103 articles. Four classes of acute care model were identified, acute-bed based care, hospital at home, emergency department in-reach and care home models. The field is dominated by small single centre randomised and non-randomised studies. Most studies were judged to be at risk of bias. A range of outcome measures were reported with little consistency between studies. Evidence of effectiveness was limited. Acute care models for older people living with frailty are heterogenous. The clinical effectiveness of these models cannot be conclusively established from the available evidence. PROSPERO registration (CRD42021279131).


[Canalicular system of enterocytes at rest and its changes during lipid absorption].
A study was made of the structural changes in different organoids of enterocytes of the rat small intestine at "rest" and during lipid absorption using ultrathin sections, impregnation with Ur-Pb-Cu, and continuous impregnation with OsO4. With the latter technique a specific canalicular system was found in the enterocytes, which we failed to observe on ultrathin sections. During lipid absorption the canalicular system underwent fragmentation. The vesicules on the trans-surface of the Golgi apparatus were enlarged, and the number of flattened cisterns was significantly lower. The changes in cellular organoids and their interrelations observed in the present study support the earlier hypothesis of the resynthesis of triglycerides within the enterocytes, the formation of chylomicrons and their transfer into the intercellular space.


The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.
Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.


Effects of varying dietary undegradable protein on dry matter intake, growth, and carcass composition of Holstein calves.
The objective was to study the effect of feeding diets varying in rumen undegradable protein on DMI, growth, feed efficiency, and carcass composition in Holstein calves from birth to 25 wk of age. Sixty Holstein calves were assigned in a randomized complete block design to one of three dietary treatment groups that differed in rumen undegradable protein as a percentage of total protein. Protein undegradabilities of the TMR fed for ad libitum intake for period 1 (wk 1 to 12 of age) were 33, 37, and 46% and for period 2 (wk 14 to 25 of age) were 30, 34, and 38%. Intake was not different among diets during period 1. During period 2, animals fed the highest and lowest levels of undegradable protein diet consumed less DM, and those animals on the highest undegradable diet had the least amount of crude protein intake. Feed efficiency was increased with increasing rumen undegradable protein for period 2. Carcass composition was not affected by dietary treatment for either 9-10-11 rib section or the half carcass. Prediction equations for carcass protein and fat were calculated for 25-wk Holstein calves using urea space and live weight. These results indicate that the amount of undegradable intake protein currently recommended for growing dairy replacements may not be justified when intake is ad libitum. In the present study, urea space was not found to be beneficial over live weight for predicting carcass protein and fat in intact male or female Holstein calves.


Population shift in mannose-specific fimbriated phase of Klebsiella pneumoniae during experimental urinary tract infection in mice.
The infection rate (percentage of mice shedding 10(5) organisms per ml of urine) in 27 mice infected intravesicularly with a mannose-specific (MS+) phenotype of Klebsiella pneumoniae was 85% at day 7, and all the bacteria shed during the 7 days exhibited strong MS activity as estimated by a yeast aggregation assay. In contrast, the outcome of infection with an MS- phenotype of the same strain in 47 mice was heterogeneous: one group of 25 mice continued to shed the originally injected phenotype (MS-) throughout the investigation period, whereas the second group (22 mice) shed bacteria with various degrees of phenotypic conversion to MS+. In the first group, the rate of infection at day 7 was significantly reduced (28%) compared with that of the second group (68%). Mice infected with a mixture of 5% MS+ bacteria and 95% of an MS- variant which lost its ability to undergo phase variation had an infection rate of 89%, but at day 7 95% of the excreted bacteria were MS+. The infection rate of mice injected with the MS- variant was 14%, and none of the mice shed MS+ bacteria. The incidence of kidney pathology was higher in mice inoculated with the MS+ phenotype (3 of 10) or in the group in which the MS+ overgrew the MS- phenotype (4 of 10) as compared with the group of mice in which no such shift occurred (1 of 11). The kidneys of four mice which excreted mostly MS+ organisms harbored a population predominantly of the MS- phenotype. These results suggest that the MS adhesin confers an advantage in the initial steps of the infectious process in the bladder but not in later stages of infection in the kidney, emphasizing the importance of phase variation in the survival of bacteria at the various stages of the infectious process.


Conservative versus invasive treatment of primary spontaneous pneumothorax: a retrospective cohort study.
The best management of primary spontaneous pneumothorax is unclear. Conservative treatment has been proposed, but no studies comparing conservative with invasive management have been carried out where pneumothorax size has been numerically quantified. This study aimed to evaluate the feasibility of conservative management for primary spontaneous pneumothoraces of any size. Retrospective cohort study of adult patients with primary spontaneous pneumothorax treated at an Australian tertiary hospital from 2006-2011, carried out by case-note and chest radiograph review. Patient demographics, smoking status, and outcome data were collected. Pneumothorax size was calculated using the Collins method, based on the sum of interpleural distances. One hundred and twenty-seven episodes from 116 patients were identified. Males (86) comprised 75% of patients, and the median age at presentation was 37 years. Eighty-two percent of cases (106) were ever-smokers. Of the episodes in which pre-treatment radiographs were available, 53 were treated conservatively and 58 invasively with tube thoracostomy, and all were clinically stable. When cases were stratified by pneumothorax size, age, sex, ethnicity, and smoking status had no effect on outcome. Compared to invasive treatment, conservative management resulted in no complications, an equal recurrence rate, and a significantly shorter length of stay. Our results suggest that it may be feasible to adopt a conservative approach as the first-line treatment of primary spontaneous pneumothorax in clinically stable patients. However, given the limitations of this study, a large randomised controlled trial is required to conclusively prove this assertion.


Comparing Clinical Characteristics and Outcomes of Young-onset and Late-onset Colorectal Cancer: An International Collaborative Study.
Compared with the general population, the incidence of young-onset (YO) colorectal cancer (CRC) is increasing. However, a significant knowledge gap exists in the clinical characteristics, treatment patterns, and outcomes for these patients. Six international tertiary cancer centers conducted a retrospective study. Patients with YO CRC (aged 18-44 years) and LO CRC (aged > 44 years) diagnosed with histologically proven colorectal adenocarcinoma from June 2003 to June 2014 were enrolled. Patients were randomly chosen from each center's database, and the patient demographics and treatment information were collected. The data were then centralized, and the final analysis was performed at a single institution. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival and mortality, and YO was compared with LO. Site-specific HRs were pooled using a random-effects meta-analysis. Overall, 498 patients, including 224 with YO (129 men; mean age, 37 ± 5.5 years) and 274 with LO (167 men; mean age, 64.8 ± 9.5 years) CRC, were included. At the diagnosis, 137 patients (61.2%) and 122 patients (44.5%) with YO and LO CRC had metastatic disease, respectively. For both cohorts, the 3 most common presenting symptoms were pain, hematochezia, and weight loss. Surgery was performed in 141 YO (63.0%) and 219 LO (79.9%) patients. The longitudinal noncurative treatment patterns were similar, but more biologic therapy was used for these YO patients. The pooled progression-free survival analysis results for first-line noncurative treatment favored LO (HR, 1.96; 95% CI, 1.04-3.68). The mortality analysis showed no significant differences between the 2 groups (YO: HR, 1.53; 95% CI, 0.91-2.58). Despite similar treatment patterns and survival outcomes, YO disease might be clinically more aggressive.


Plasma leptin levels in pigs with different leptin and leptin receptor genotypes.
A C3469T mutation at exon 3 of the pig leptin (Lep) gene has been genotyped in diverse pig breeds yielding controversial results with regard to its association with growth, fatness and carcass traits. A similar situation has been reported for a HpaII restriction fragment length polymorphism (RFLP) in the pig leptin receptor (Lepr) gene, where associations were found depending on the statistical model employed. The main objective of our work was to investigate if leptin plasma concentrations differ in pigs with different C3469T and Lepr HpaII RFLP genotypes. With this aim, we have measured plasma leptin levels at 160 days in 68 Landrace pigs with different Lep C3469T and Lepr HpaII RFLP genotypes. Neither Lep (TT: 11.68 ng/ml, TC: 10.71 ng/ml) nor Lepr (AA: 12.6 ng/ml, AB: 10.93 ng/ml, BB: 11.74 ng/ml) genotypes influenced significantly plasma Lep concentration. Moreover, we did not find any association between Lep and Lepr genotypes and phenotypic variation at growth and fatness traits in a commercial population of 320 Landrace pigs.


Expression of CSF-I and CSF-I receptor by normal lactating mammary epithelial cells.
Previous studies suggested a potential role for macrophage colony stimulating factor (CSF-1) in lactogenic differentiation of the breast. The aim of this study was to define the regulation of CSF-1 and its receptor (CSF-1R, the product of c-fms proto-oncogene) by lactogenic hormones in the breast in vivo during pregnancy and lactation and in vitro in organ culture and mammary epithelial cell lines. Immunohistochemical staining assays for the expression of CSF-1 and CSF-1R antigens were performed on sections of breast biopsies from nonpregnant (n = 10), prepartum (n = 4), and postpartum lactating patients (n = 7) and on sections of human mammary glands cultured in the presence of the lactogenic hormones insulin, prolactin, and glucocorticoids. Northern blot analyses were used to study the regulation of CSF-1 and CSF-1R by these same lactogenic hormones in normal and neoplastic mammary epithelial cell lines in cell culture. Normal, nonlactating mammary epithelium did not express CSF-1R and synthesized only low levels of CSF-1. During lactation, significant levels of both proteins could be observed in the epithelial cells that line actively lactating ducts and alveoli. Very similar increases in epithelial cell expression of CSF-1 and CSF-1R were observed in organ cultures of normal mammary gland biopsies exposed to prolactin, insulin, and glucocorticoids. Colony stimulating factor mRNA levels were increased by prolactin and/or insulin in a normal mammary epithelial cell line, while glucocorticoids had no apparent effect on CSF-1 mRNA levels. In contrast, we found that the levels of CSF-1R transcript are regulated primarily by glucocorticoids in breast carcinoma cells, while prolactin merely modulates the glucocorticoid effect. The observed increases in the expression of CSF-1 and its receptor during lactogenesis and the regulation of CSF-1/CSF-1R by lactogenic hormones suggests that this cytokine/receptor pair might play a regulatory role in the cellular events leading to the lactogenic differentiation of mammary epithelial cells.


Geometric optics of thermal blooming in gases. Part 1.
Thermal blooming is considered for the cases of with and without wind transverse to the beam propagation from the point of view of fluid dynamics of a compressible gaseous system and the coupling of this with geometric optics using eikonal formalism. Full compressible fluid dynamic relationships are developed (first-order perturbation approximation) with kinetics of energy relaxation from vibrational levels into heat and with thermal conductivity of a compressible gas as a heat loss mechanism. Eikonal theory is examined from the point of view of paraxial treatmen t in rigorous form, and some analytical beam intensity relationships are derived. In the process, several questions on the formation of caustics and thick lens effects are resolved. As a consequence of the above, a general time dependent model for the interaction of a laser beam with a compressible absorbing medium in the presence of wind is developed, and certain time dependent analytical solutions are obtained. These solutions reduce to the plain hermal blooming case with no wind and for long times to steady state wind case that has been previously reported by others to various degrees of correctness [F. G. Gebhardt and D. C. Smith, Appl. Phys. Lett. 14, 52 (1969); D. C. Smith, IEEE J. Quantum Electron. QE-5, 600 (1969)].


Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus.
Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population. The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood. Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells. Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus. The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans.


In vivo and in vitro protein imaging in thermophilic archaea by exploiting a novel protein tag.
Protein imaging, allowing a wide variety of biological studies both in vitro and in vivo, is of great importance in modern biology. Protein and peptide tags fused to proteins of interest provide the opportunity to elucidate protein location and functions, detect protein-protein interactions, and measure protein activity and kinetics in living cells. Whereas several tags are suitable for protein imaging in mesophilic organisms, the application of this approach to microorganisms living at high temperature has lagged behind. Archaea provide an excellent and unique model for understanding basic cell biology mechanisms. Here, we present the development of a toolkit for protein imaging in the hyperthermophilic archaeon Sulfolobus islandicus. The system relies on a thermostable protein tag (H5) constructed by engineering the alkylguanine-DNA-alkyl-transferase protein of Sulfolobus solfataricus, which can be covalently labeled using a wide range of small molecules. As a suitable host, we constructed, by CRISPR-based genome-editing technology, a S. islandicus mutant strain deleted for the alkylguanine-DNA-alkyl-transferase gene (Δogt). Introduction of a plasmid-borne H5 gene in this strain led to production of a functional H5 protein, which was successfully labeled with appropriate fluorescent molecules and visualized in cell extracts as well as in Δogt live cells. H5 was fused to reverse gyrase, a peculiar thermophile-specific DNA topoisomerase endowed with positive supercoiling activity, and allowed visualization of the enzyme in living cells. To the best of our knowledge, this is the first report of in vivo imaging of any protein of a thermophilic archaeon, filling an important gap in available tools for cell biology studies in these organisms.


The origin of long-period lattice spacings observed in iron-carbide nanowires encapsulated by multiwall carbon nanotubes.
Structures comprising single-crystal, iron-carbon-based nanowires encapsulated by multiwall carbon nanotubes self-organize on inert substrates exposed to the products of ferrocene pyrolysis at high temperature. The most commonly observed encapsulated phases are Fe₃C, α-Fe, and γ-Fe. The observation of anomalously long-period lattice spacings in these nanowires has caused confusion since reflections from lattice spacings of ≥ 0.4 nm are kinematically forbidden for Fe₃C, most of the rarely observed, less stable carbides, α-Fe, and g-Fe. Through high-resolution electron microscopy, selective area electron diffraction, and electron energy loss spectroscopy we demonstrate that the observed long-period lattice spacings of 0.49, 0.66, and 0.44 nm correspond to reflections from the (100), (010), and (001) planes of orthorhombic Fe₃C (space group Pnma). Observation of these forbidden reflections results from dynamic scattering of the incident beam as first observed in bulk Fe₃C crystals.With small amounts of beam tilt these reflections can have significant intensities for crystals containing glide planes such as Fe₃C with space groups Pnma or Pbmn.


Carcinoid tumors: a 37-year experience.
We analyzed 101 cases of carcinoid tumor in patients treated at the University of Chicago hospitals between 1942 and 1979. Tumors occurred most commonly in the rectum (29%) and ileum (28%). Only 12% were appendiceal. More than 60% were less than 1 cm, and 43% were confined to the submucosa. These factors led to favorable prognoses. Twenty-three percent of the tumors were greater than 2 cm in diameter; 70% of them had metastasized, compared with only 6% of lesions less than 1 cm. Metastases were present in 46% of ileal and 40% of colonic lesions. None of 13 bronchial and only one of 12 appendiceal lesions demonstrated this spread. Carcinoid syndrome was noted in three cases. A second neoplasm was present in 22%. The corrected five-year survival rate was 87% overall, 95% without metastases, 83% with positive regional lymph nodes, and only 40% with distant spread.


Concentrations of cardiac Troponin I before and after ovariohysterectomy in 46 female dogs with pyometra.
Canine pyometra is a common disease in countries where routine spaying of young dogs is not common practice. This disease is known to lead to systemic inflammation potentially affecting multiple organs in the body, including the heart. Cardiac-specific Troponin I (cTnI) is a sensitive marker of myocardial cell damage, which can result from ischemia, trauma, toxins or inflammation. Dogs with pyometra are also exposed to anaesthesia which can potentially result in myocardial cell damage. The aims of the study were 1) to evaluate the occurrence of myocardial cell damage as indicated by increased serum concentrations of cTnI in dogs with pyometra and relate these to presence of systemic inflammation and 2) to evaluate the change in cTnI-concentrations after anaesthesia and surgery. Serum cTnI concentration was measured preoperatively and one day after surgery in 46 female dogs with pyometra and 15 female dogs that underwent surgery for other reasons (ovariohysterectomy and mammary tumours). Forty-six female dogs of different breeds diagnosed with pyometra were included. The dogs had a median age of 8.5 years (IQR 7.5-10) and a median weight of 29 kg (IQR 9-32). Of the 46 dogs, 37 (80%) fulfilled the chosen criteria for systemic inflammatory response syndrome (SIRS) at inclusion. Thirteen (28%) of the dogs had increased cTnI concentrations (> 0.2 microg/l) before surgery and 18 (39%) had increased cTnI-concentrations the day after surgery. The cTnI concentrations in the 13 dogs with increased preoperative cTnI concentrations decreased in 8 dogs, increased in 4 dogs, and was unchanged in one dog. Seven dogs with nondetectable preoperative cTnI concentrations had increased postoperative concentrations. The only significant association between the studied laboratory or clinical variables (including SIRS) and cTnI concentration was preoperative percentage band neutrophils (PBN) and postoperative cTnI concentration (P = 0.016). In total, 20 dogs (43%) had increased pre- or postoperative cTnI concentrations. Seven dogs (15%) had pre-or postoperative concentrations of cTnI of 1.0 microg/l or higher. Mild to moderate increases in cTnI appears to be common in dogs with pyometra before and after surgery, but the clinical importance of this finding is uncertain. None of the studied clinical variables were found to reliably predict increased preoperative cTnI concentrations. Because of the pre- and postoperative variation in cTnI concentrations, it was not possible to identify a negative effect of anaesthesia and surgery on myocardial cell integrity.


Different MRF4 knockout alleles differentially disrupt Myf-5 expression: cis-regulatory interactions at the MRF4/Myf-5 locus.
Three different null alleles of the myogenic bHLH gene MRF4/herculin/Myf-6 were created recently. The three alleles were similar in design but were surprisingly different in the intensity of their phenotypes, which ranged from complete viability of homozygotes to complete lethality. One possible explanation for these differences is that each mutation altered expression from the nearby Myf-5 gene to a different extent. This possibility was first raised by the observation that the most severe MRF4 knockout allele expresses no Myf-5 RNA and is a developmental phenocopy of the Myf-5 null mutation. Furthermore, initial studies of the two weaker alleles had shown that their differences in viability correlate with the intensity of rib skeletal defects, and the most extreme version of this rib defect is the hallmark phenotype of Myf-5 null animals. In the present study we tested this hypothesis for the two milder MRF4 alleles. By analyzing compound heterozygous animals carrying either the intermediate or the weakest MRF4 knockout allele on one chromosome 10 and a Myf-5 knockout allele on the other chromosome, we found that both of these MRF4 alleles apparently downregulate Myf-5 expression by a cis-acting mechanism. Compound heterozygotes showed increased mortality of the normally viable MRF4 allele, together with intensified rib defects for both MRF4 alleles and increased deficits in myotomal Myf-5 expression. The allele-specific gradation in phenotypes also suggested that rib morphogenesis is profoundly sensitive to quantitative differences in Myf-5 function if Myf-5 products drop below hemizygous levels. The mechanistic basis for cis interactions at the MRF4/Myf-5 locus was further examined by fusing a DNA segment containing the entire MRF4 structural gene, including all sequences deleted in the three MRF knockout alleles, with a basal promoter and a lacZ reporter. Transgenic embryos showed specific LacZ expression in myotomes in a pattern that closely resembles the expression of Myf-5 RNA. cis-acting interactions between Myf-5 and MRF4 may therefore play a significant role in regulating expression of these genes in the early myotomes of wildtype embryos.


Effects of communities, neighborhoods and stores on retail pricing and promotion of beer.
This study examines how communities, neighborhoods and stores influence retail pricing and promotion of beer. In the year 2000, trained field staff conducted observations in 2,024 retail alcohol stores in 160 communities throughout the contiguous United States. Based on a nationally representative sample of schools, we selected communities defined by the school's catchment area, or the vicinity from which the majority of students are drawn. We randomly selected off-sale alcohol retail establishments from a complete list of stores likely to sell tobacco or alcohol in the selected communities. Beer price and promotions are based on observations of Miller and Budweiser beer brands in the stores. Neighborhoods are defined by the store's census block. We used cross-sectional, hierarchical regression models and mixed methods procedures to analyze data. Community, neighborhood and store characteristics were related to beer price; however, only community and store characteristics were predictive of beer promotions. Overall, the pricing and promotion of beer vary systematically by some characteristics of communities, neighborhoods and stores, but not significantly by the number of young people populating a neighborhood. In addition, pricing and promotion of Budweiser and Miller beers, in particular, do not appear to target racial minority populations. Because of the significant effect of store characteristics, public health agencies and advocates might focus prevention efforts on collaborations with liquor control agencies to reduce variations in pricing and promotion of beer, which ultimately encourage risky drinking behaviors. Further studies are needed to examine the effects of pricing and promotion on alcohol-related social problems.


Simulation to Predict Effect of Citywide Events on Emergency Department Operations.
Medical emergency preparedness has been an issue of medical relevance since the advent of hospital care. Studies have simulated emergency department (ED) overcrowding but not yet characterized effects of large-scale, planned events that drastically alter a city's demography, such as in Philadelphia, Pennsylvania during the 2015 World Meeting of Families. A discrete event simulation of the ED at the Children's Hospital of Philadelphia was designed and validated using past data. The model was used to predict the patient length of stay (LOS) and number of admitted patients if the arrival stream to the ED were to change by 50% from typical arrivals in either direction. We compared the model's estimations with data produced during the papal visit that had 39.65% fewer patient arrivals. For validation, the simulated mean LOS was 226.1 ± 173.3 minutes (mean ± SD) for all patients and 352.1 ± 170.3 minutes for admitted patients. Real-world mean LOSs for the fiscal year 2014 were 230.6 ± 134.8 for all patients and 345.0 ± 147.7 for admitted patients. For the estimation of the World Meeting of Families, the simulation accurately estimated the LOS of both patients overall and admitted patients within 10%. These results show that it is possible to use simulations to project the patient flow effects in EDs in case of large-scale events. Providing efficient care is essential to emergency operations, and projections of demand are crucial for targeting appropriate changes during large-scale events. Analysis of validated computer simulations allows for evidence-based decision making in a complex clinical environment.


3D/4D sonography moved prenatal diagnosis of fetal anomalies from the second to the first trimester of pregnancy.
The introduction of 3D/4D sonography with high frequency transvaginal transducer has resulted in remarkable progress in ultrasonographic visualization of early embryos and fetuses and development of new fields of 3D sonoembryology. With the proper use of this new diagnostic modality and with experienced examiner, both structural and functional development in the first trimester of gestation can be assessed more objectively and reliable. Indeed new technology moved embryology from postmortem studies to the in vivo environment. Furthermore, there are good reasons to believe that 3D/4D sonography moved prenatal diagnosis of fetal abnormalities from the second to the first trimester of pregnancy. We will try to illustrate it with the number of convincing slides.


Hereditary geniospasm: linkage to chromosome 9q13-q21 and evidence for genetic heterogeneity.
Hereditary geniospasm is an unusual movement disorder causing episodes of involuntary tremor of the chin and the lower lip. Episodes typically start in early childhood and may be precipitated by stress, concentration, and emotion. Hereditary geniospasm is inherited as an autosomal dominant trait, and its cause is not known. We report the results of a genomewide genetic linkage study in a four-generation British family with hereditary geniospasm. Positive two-point LOD scores were obtained for 15 microsatellite markers on the peri-centromeric region of chromosome 9. A maximum two-point LOD score of 5.24 at theta = .00 was obtained for the marker D9S1837. Construction of haplotypes defined an interval of 2.1 cM between the flanking markers D9S1806 and D9S175, thus assigning one locus for hereditary geniospasm to the proximal long arm of chromosome 9q13-q21. Hereditary geniospasm in a second British family is not linked to this region, indicating genetic heterogeneity. These findings may have implications for other inherited focal movement disorders that as yet remain unmapped.


Are there more members of the CNTF-GPA family?
Ciliary neurotrophic factor (CNTF) and growth promoting activity (GPA) are two members of a family of structurally and functionally related cytokines. Although the primary sequences of these proteins are only distantly related, many share striking functional similarities. The question of the potential existence of more, as yet undiscovered, members of this family, especially those most related to CNTF, is discussed. There are several biological systems which exhibit unexplained CNTF-like activities. This has led to speculation that there are indeed other CNTF-like proteins to be found. Because of the poor primary sequence conservation among known members of this family, even those sharing strong functional similarities, it is unlikely that a cloning approach based on sequence homology will find these putative new members of the family. Instead, a more biological approach, based on functional similarities, is more likely to succeed.


Endogenous thymidine and hypoxanthine are a source of error in evaluating methotrexate cytotoxicity by clonogenic assays using undialyzed fetal bovine serum.
None of 13 fresh human tumor samples of various histology cloned in a two-layer agar culture system with 20% undialyzed fetal bovine serum (FBS) showed sensitivity to three antifolates, methotrexate (MTX), trimetrexate and 5,8-dideazaisofolic acid (IAHQ), even after continuous exposure to the highest concentrations (100 microM) for 21 days. In order to investigate this lack of antifolate drug effect, we compared the toxicity of continuous MTX exposure in the human colon carcinoma cell line HCT-8, cloned in a thymidineless medium (RPMI 1640) supplemented with 10% horse serum (HS), 10% fetal bovine serum (FBS), 20% FBS or 20% dialyzed FBS. In the presence of native FBS, when the minimum clone size was set at 30 cells/colony, the survival of HCT-8 cells reached a plateau at approximately 60% of untreated control after exposure to MTX concentrations between 0.1 microM and 100 microM. Only when the minimum clone size was set at 2 X 10(3) cells/colony was the sensitivity of HCT-8 cells to the antimetabolite comparable to that obtained in HS or dialyzed FBS (ED50 values in the range of 0.01 microM). MTX protection experiments indicated that even very small concentrations of thymidine and hypoxanthine together were sufficient to reproduce the pattern of sensitivity to MTX observed under culture conditions with undialyzed FBS. We conclude that for a proper evaluation of MTX cytotoxicity in clonogenic assays, dialyzed FBS and thymidine-less media should be employed; if native FBS is an absolute requirement for growth, only very large colonies (at least 10 cell divisions) should be scored.


Dietary folate levels alter the kinetics and molecular mechanism of prostate cancer recurrence in the CWR22 model.
Folate impacts the genome and epigenome by feeding into one-carbon metabolism to produce critical metabolites, deoxythymidine monophosphate and s-adenosylmethionine. The impact of folate exposure and intervention timing on cancer progression remains controversial. Due to polyamine metabolism's extraordinary biosynthetic flux in prostate cancer (CaP) we demonstrated androgen stimulated CaP is susceptible to dietary folate deficiency. We hypothesized dietary folate levels may also affect castration recurrent CaP. We used the CWR22 human xenograft model which recurs following androgen withdrawal. Engrafted mice were fed a folate depleted or supplemented diet beginning at androgen withdrawal, or prior to xenograft implantation. Both folate depletion and supplementation at the time of withdrawal significantly decreased recurrence incidence. Folate supplementation prior to xenograft implantation increased time to recurrence, suggesting a protective role. By contrast, folate depleted recurrent tumors exhibited transcriptional adaptive responses that maintained high polyamine levels at the expense of increased DNA damage and DNA methylation alterations. Mining of publically available data demonstrated folate related pathways are exceptionally dysregulated in human CaP, which correlated with decreased time to biochemical recurrence. These findings highlight the potential for novel therapeutic interventions that target these metabolic pathways in CaP and provide a rationale to apply such strategies alongside androgen withdrawal.


PET/MRI in the Presence of Metal Implants: Completion of the Attenuation Map from PET Emission Data.
We present a novel technique for accurate whole-body attenuation correction in the presence of metallic endoprosthesis, on integrated non-time-of-flight (non-TOF) PET/MRI scanners. The proposed implant PET-based attenuation map completion (IPAC) method performs a joint reconstruction of radioactivity and attenuation from the emission data to determine the position, shape, and linear attenuation coefficient (LAC) of metallic implants. Methods: The initial estimate of the attenuation map was obtained using the MR Dixon method currently available on the Siemens Biograph mMR scanner. The attenuation coefficients in the area of the MR image subjected to metal susceptibility artifacts are then reconstructed from the PET emission data using the IPAC algorithm. The method was tested on 11 subjects presenting 13 different metallic implants, who underwent CT and PET/MR scans. Relative mean LACs and Dice similarity coefficients were calculated to determine the accuracy of the reconstructed attenuation values and the shape of the metal implant, respectively. The reconstructed PET images were compared with those obtained using the reference CT-based approach and the Dixon-based method. Absolute relative change (aRC) images were generated in each case, and voxel-based analyses were performed. Results: The error in implant LAC estimation, using the proposed IPAC algorithm, was 15.7% ± 7.8%, which was significantly smaller than the Dixon- (100%) and CT- (39%) derived values. A mean Dice similarity coefficient of 73% ± 9% was obtained when comparing the IPAC- with the CT-derived implant shape. The voxel-based analysis of the reconstructed PET images revealed quantification errors (aRC) of 13.2% ± 22.1% for the IPAC- with respect to CT-corrected images. The Dixon-based method performed substantially worse, with a mean aRC of 23.1% ± 38.4%. Conclusion: We have presented a non-TOF emission-based approach for estimating the attenuation map in the presence of metallic implants, to be used for whole-body attenuation correction in integrated PET/MR scanners. The Graphics Processing Unit implementation of the algorithm will be included in the open-source reconstruction toolbox Occiput.io.


Thalamic and cortical contributions to neural plasticity after limb amputation.
Little is known about the substrates for the large-scale shifts in the cortical representation produced by limb amputation. Subcortical changes likely contribute to the cortical remodeling, yet there is little data regarding the extent and pattern of reorganization in thalamus after such a massive deafferentation. Moreover, the relationship between changes in thalamus and in cortex after injuries of this nature is virtually unexplored. Multiunit microelectrode maps were made in the somatosensory thalamus and cortex of two monkeys that had long-standing, accidental forelimb amputations. In the deprived portion of the ventroposterior nucleus of the thalamus (VP), where stimulation to the hand would normally activate neurons, new receptive fields had emerged. At some recording sites within the deprived zone of VP, neurons responded to stimulation of the remaining stump of the arm and at other sites neurons responded to stimulation of both the stump and the face. This same overall pattern of reorganization was present in the deprived hand representation of cortical area 3b. Thus thalamic changes produced by limb amputation appear to be an important substrate of cortical reorganization. However, a decrease in the frequency of abnormal stump/face fields in area 3b compared with VP and a reduction in the size of the fields suggests that cortical mechanisms of plasticity may refine the information relayed from thalamus.


Calculating radiotherapy margins based on Bayesian modelling of patient specific random errors.
Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement ('random error') than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.


An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis.
Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 ((1-78)REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated (1-78)REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.


Trend in active transportation to school among Swiss school children and its associated factors: three cross-sectional surveys 1994, 2000 and 2005.
Giving the rising trend in childhood obesity in many countries including Switzerland, strategies to increase physical activity such as promoting active school travel are important. Yet, little is known about time trends of active commuting in Swiss schoolchildren and factors associated with changes in walking and biking to school. Between 1994 and 2005, information about mobility behaviour of children aged 6-14 years was collected within three Swiss population based national travel behaviour surveys. Mode of transport to school was reported for 4244 children. Weighted multivariate logistic regression analyses were used to assess active school travel time trends and their influencing factors. More than 70% of Swiss children walked or biked to school. Nevertheless, the proportion of children biking to school decreased (p = 0.05, linear trend), predominately in urban areas, and motorized transportation increased since 1994 (p = 0.02). Distance to school did not change significantly over time but availability of bikes decreased (p < 0.001) and number of cars per household increased (p < 0.001). The association between survey year and bike use was significantly modified by living in an urban area (OR (95%CI): 1.0, 0.63 (0.44-0.90), 0.71 (0.49-1.03), respectively for 1994, 2000 and 2005) and by distance to school (OR (95%CI): 1.0, 0.65 (0.40-1.05), 0.50 (0.23-0.79) for the same years and for children who lived more than a mile away from school). Programs to encourage safe biking and to limit car use as mode of transport to school are warranted to stop this trend.


Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.
Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.


Electrically tunable tunneling rectification magnetoresistance in magnetic tunneling junctions with asymmetric barriers.
The development of multifunctional spintronic devices requires simultaneous control of multiple degrees of freedom of electrons, such as charge, spin and orbit, and especially a new physical functionality can be realized by combining two or more different physical mechanisms in one specific device. Here, we report the realization of novel tunneling rectification magnetoresistance (TRMR), where the charge-related rectification and spin-dependent tunneling magnetoresistance are integrated in Co/CoO-ZnO/Co magnetic tunneling junctions with asymmetric tunneling barriers. Moreover, by simultaneously applying direct current and alternating current to the devices, the TRMR has been remarkably tuned in the range from -300% to 2200% at low temperature. This proof-of-concept investigation provides an unexplored avenue towards electrical and magnetic control of charge and spin, which may apply to other heterojunctions to give rise to more fascinating emergent functionalities for future spintronics applications.


Association of formal and informal care with health-related quality of life and depressive symptoms: findings from the Caring for Adults Recovering from the Effects of Stroke study.
To investigate the association between informal and formal care and stroke participants' self-reported health-related quality of life and depressive symptoms one year after the stroke event. We examined a national population-based sample of 123 stroke participants. Care received was defined as formal (outpatient therapy, care from home health aides, nurses, or therapists), informal (family caregiver), or shared (formal and informal). Hours of care were extracted from Medicare claims and caregiver self-report. A general linear model was used to compare health-related quality of life and depressive symptoms one year after the stroke for those who received shared care, only informal care or only formal care to those with no post-stroke care. Among stroke participants, 12.2% received only formal care, 35.0% only informal care, 38.2% shared care, and 14.6% no care. Those with only informal care had greater self-reported depressive symptoms than those who received no care at all. Shared care was the most common care configuration for stroke participants, but no significant associations were found between shared care and self-reported outcomes after adjusting for stroke participant characteristics. Further research is needed on the dose of informal and formal care and their coordination to better understand relationships with recovery.IMPLICATIONS FOR REHABILITATIONStroke is one of the leading causes of disability for adults in the USA and ongoing care is needed for survivors.Informal caregivers such as family members play an important role in recovery in addition to formal care provided by home health aides, nurses and therapists.This study showed that survivors with informal care had more severe depressive symptoms, while shared care provided by formal and informal caregivers may prevent further decline in patients with worse baseline health.


Maternal and Fetal Outcomes Among Pregnant Women With Human Monkeypox Infection in the Democratic Republic of Congo.
Human monkeypox is an endemic disease in rain-forested regions of central Democratic Republic of Congo. We report fetal outcomes for 1 of 4 pregnant women who participated in an observational study at the General Hospital of Kole (Sankuru Province), where 222 symptomatic subjects were followed between 2007 and 2011. Of the 4 pregnant women, 1 gave birth to a healthy infant, 2 had miscarriages in the first trimester, and 1 had fetal death, with the macerated stillborn showing diffuse cutaneous maculopapillary skin lesions involving the head, trunk and extremities, including palms of hands and soles of feet.


Oncologists' and family physicians' views on value for money of cancer and congestive heart failure care.
Previous studies suggest that cancer-related interventions are valued by policy makers more favorably than interventions for other medical conditions, but the views of practicing physicians have not yet been assessed in Israel. Attitudes and judgments of practicing physicians may assist decision-makers in their deliberations on coverage of new technologies. We conducted a national survey in Israel among oncologists and family physicians to explore their views on access to care, coverage decisions and treatment recommendations for cancer and congestive heart failure (CHF) patients. We administered a web-based survey to 300 family physicians and 156 oncologists. The questionnaire included 24 statements and physicians were asked to indicate their level of agreement with each statement on a 5-point Likert scale, ranging from "strongly agree" to "strongly disagree". Where relevant, physicians were asked to express their views on interventions for cancer and CHF respectively. Response rates were 39% for family physicians and 36% for oncologists. Participants expressed similar views on cancer and CHF care and no significant differences were found between the two medical specialties. More than 85% of physicians believe that inclusion of a treatment in the National List of Health Services (NLHS) strongly affects their patients' access to care. Approximately 80% suggest that more use of comparative-effectiveness and cost-effectiveness analysis is needed in coverage decisions. The vast majority of respondents (75%) suggest that assessment of value-for-money should be made by an independent (academic) institution or the national committee responsible for recommending coverage decisions, Seventy percent believe that treatments not included in the NLHS should be included in supplementary health insurance programs and only a small minority of respondents (<30%) believe that cancer-related interventions should receive higher priority than non-cancer interventions in coverage decisions. Our findings suggest that both oncologists and family physicians value cancer and CHF interventions equally. We could not find evidence for a "cancer premium" as implied from previous surveys and analysis of coverage decisions in various countries.


Components of the IFN-gamma signaling pathway in tumorigenesis.
Many features of the interferon gamma (IFN-gamma) signaling pathway would suggest that it is anti-tumorigenic. The IFN-gamma signaling pathway leads to apoptosis and to the expression of immune function proteins that could cooperate with T cells in the destruction of tumor. Various lines of experimental approach have, in general, supported the hypothesis that the IFN-gamma signaling pathway is anti-tumorigenic. However, data also indicate that the idea that the IFN-gamma signaling pathway is exclusively anti-tumorigenic is too simplistic. Also, to date, very little of the knowledge regarding the anti-tumor effects of the IFN-gamma pathway has been useful in the prognosis or therapy of cancer. This review summarizes the current state of knowledge regarding the IFN-gamma signaling pathway in tumorigenesis, with an emphasis on MHC class II induction in tumor cells and the induction of apoptosis in tumor cells. The review also indicates some future areas of investigation that offer hope for applying this knowledge in reducing cancer mortality.


reconCNV: interactive visualization of copy number data from high-throughput sequencing.
Copy number variation (CNV) is an important category of unbalanced structural rearrangement. While methods for detecting CNV in high-throughput targeted sequencing have become increasingly sophisticated, dedicated tools for interactive and dynamic visualization of CNV from these data are still lacking. We describe reconCNV, a tool that produces an interactive and annotated web-based dashboard for viewing and summarizing CNVs detected in next-generation sequencing (NGS) data. reconCNV is designed to work with delimited result files from most NGS CNV callers with minor adjustments to the configuration file. The reconCNV output is an HTML file that is viewable on any modern web browser, requires no backend server, and can be readily appended to existing analysis pipelines. In addition to a standard CNV track for visualizing relative fold change and absolute copy number, the tool includes an auxiliary variant allele fraction track for visualizing underlying allelic imbalance and loss of heterozygosity. A feature to mask assay-specific technical artifacts and a direct HTML link out to the UCSC Genome Browser are also included to augment the reviewer experience. By providing a light-weight plugin for interactive visualization to existing NGS CNV pipelines, reconCNV can facilitate efficient NGS CNV visualization and interpretation in both research and clinical settings. The source code and documentation including a tutorial can be accessed at https://github.com/rghu/reconCNV as well as a Docker image at https://hub.docker.com/repository/docker/raghuc1990/reconcnv. Supplementary data are available at Bioinformatics online.


Giant extramedullary arteriovenous fistula supplied by the anterior spinal artery: treatment by detachable balloons.
A case of a large extramedullary arteriovenous fistula in a young man, which was deemed inoperable, is described. The fistula was mainly supplied by the anterior spinal artery and was responsible for a progressive myeloradicular syndrome. Successful treatment with detachable balloons was carried out. Along with this case report, a review is made of the different types of extramedullary arteriovenous fistulas and their treatment based upon 11 cases seen at Lariboisière Hospital: type 1 is a plain small fistula where embolization is contraindicated; type 2 shows an enlarged anterior spinal artery with dysplastic vein and may be embolized with solid particles; type 3 is a very large multipediculated fistula where the best treatment seems to be detachable balloons. The indications for using detachable balloons for temporary occlusion and for definitive treatment are reviewed. Special emphasis is placed on the possibility of detaching balloons without the need for a coaxial catheter.


Enhancing OSA Assessment with Explainable AI.
Explainable Artificial Intelligence (xAI) is a rapidly growing field that focuses on making deep learning models interpretable and understandable to human decision-makers. In this study, we introduce xAAEnet, a novel xAI model applied to the assessment of Obstructive Sleep Apnea (OSA) severity. OSA is a prevalent sleep disorder that can lead to numerous medical conditions and is currently assessed using the Apnea-Hypopnea Index (AHI). However, AHI has been criticized for its inability to accurately estimate the effect of OSAs on related medical conditions. To address this issue, we propose a human-centric xAI approach that emphasizes similarity between apneic events as a whole and reduces subjectivity in diagnosis by examining how the model makes its decisions. Our model was trained and tested on a dataset of 60 patients' Polysomnographic (PSG) recordings. Our results demonstrate that the proposed model, xAAEnet, outperforms models with traditional architectures such as convolutional regressor, autoencoder (AE), and variational autoencoder (VAE). This study highlights the potential of xAI in providing an objective OSA severity scoring method.Clinical relevance- This study provides an objective OSA severity scoring technique which could improve the management of apneic patients in clinical practice.


Partial monosomy 2p and partial trisomy 4q due to paternal translocation t(2;4)(p25.1;q31.3).
Clinical features in patients with segmental aneuploidy often vary depending on the size of the chromosomal segment involved. Monosomy 2p is usually observed as a part of more complex syndromes among probands of balanced reciprocal translocation carriers. Patients with dup4q syndrome have variable clinical features, which are both related to the size of duplicated segment of the 4q and specific associated monosomy. Clinical findings of our patient were compatible with those previously reported in dup4q and del2p patients. Herein are presented the clinical and cytogenetic findings in a 4-year-old female with an unbalanced karyotype 46,XX,der(2)t(2;4)(p25.1;q31.3)pat. Clinical phenotypes of 2p;4q translocation cases are variable, because the involved breakpoints vary case-by-case. We also compare similarity of the clinical features of our proband and other patients carrying either duplication of the distal part of 4q and patients carrying a deletion of distal part of 2p as described in the literature. To our knowledge, this is the first case of partial trisomy 4q accompanied with partial monosomy 2p.


Multiple foreign body ingestion and ileal perforation.
Foreign body ingestion is a common problem encountered in the pediatric age group. The swallowed object is often passed with little or no morbidity. Problems ensue if the ingested foreign body is hazardous, is multiple, or becomes impacted. We describe an ileal perforation following the ingestion of an alkaline disc battery, a magnet, and a steel ball impacted in the ileum for about 48 h. The magnet and the steel ball were attracted to each other, forming a composite unit. The disc battery and the magnet were attracted to each other across a loop of ileum, causing necrosis and perforation of the ileum.


Naturally Prefabricated Marine Biomaterials: Isolation and Applications of Flat Chitinous 3D Scaffolds from Ianthella labyrinthus (Demospongiae: Verongiida).
Marine sponges remain representative of a unique source of renewable biological materials. The demosponges of the family Ianthellidae possess chitin-based skeletons with high biomimetic potential. These three-dimensional (3D) constructs can potentially be used in tissue engineering and regenerative medicine. In this study, we focus our attention, for the first time, on the marine sponge Ianthella labyrinthus Bergquist & Kelly-Borges, 1995 (Demospongiae: Verongida: Ianthellidae) as a novel potential source of naturally prestructured bandage-like 3D scaffolds which can be isolated simultaneously with biologically active bromotyrosines. Specifically, translucent and elastic flat chitinous scaffolds have been obtained after bromotyrosine extraction and chemical treatments of the sponge skeleton with alternate alkaline and acidic solutions. For the first time, cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) have been used to test the suitability of I. labyrinthus chitinous skeleton as ready-to-use scaffold for their cell culture. Results reveal a comparable attachment and growth on isolated chitin-skeleton, compared to scaffolds coated with extracellular matrix mimetic Geltrex®. Thus, the natural, unmodified I. labyrinthus cleaned sponge skeleton can be used to culture iPSC-CMs and 3D tissue engineering. In addition, I. labyrinthus chitin-based scaffolds demonstrate strong and efficient capability to absorb blood deep into the microtubes due to their excellent capillary effect. These findings are suggestive of the future development of new sponge chitin-based absorbable hemostats as alternatives to already well recognized cellulose-based fabrics.


Commonly used anesthetics modify alcohol and (-)-trans-delta9-tetrahydrocannabinol in vivo effects on rat cerebral arterioles.
Ethyl alcohol and cannabis are widely used recreational substances with distinct effects on the brain. These drugs increase accidental injuries requiring treatment under anesthesia. Moreover, alcohol and cannabis are often used in anesthetized rodents for biomedical research. Here, we compared the influence of commonly used forms of anesthesia, injectable ketamine/xylazine (KX) versus inhalant isoflurane, on alcohol- and (-)-trans-delta9-tetrahydrocannabinol (THC) effects on cerebral arteriole diameter evaluated in vivo. Studies were performed on male and female Sprague-Dawley rats subjected to intracarotid catheter placement for drug infusion, and cranial window surgery for monitoring pial arteriole diameter. Depth of anesthesia was monitored every 10-15 min by toe-pinch. Under KX, the number of toe-pinch responders was maximal after the first dose of anesthesia and diminished over time in both males and females. In contrast, the number of toe-pinch responders under isoflurane slowly raised over time, leading to increase in isoflurane percentage until deep anesthesia was re-established. Rectal temperature under KX remained stable in males while dropping in females. As expected for gaseous anesthesia, both males and females exhibited rectal temperature drops under isoflurane. Infusion of 50 mM alcohol (ethanol, EtOH) into the cerebral circulation rendered robust constriction in males under KX anesthesia, this alcohol action being significantly smaller, but still present under isoflurane anesthesia. In females, EtOH did not cause measurable changes in pial arteriole diameter regardless of the anesthetic. These findings indicate a strong sex bias with regards to EtOH induced vasoconstriction. Infusion of 42 nM THC in males and females under isoflurane tended to constrict cerebral arterioles in both males and females when compared to isovolumic infusion of THC vehicle (dimethyl sulfoxide in saline). Moreover, THC-driven changes in arteriole diameter significantly differed in magnitude depending on the anesthetic used. Simultaneous administration of 50 mM alcohol and 42 nM THC to males constricted cerebral arterioles regardless of the anesthetic used. In females, constriction by the combined drugs was also observed, with limited influence by anesthetic presence. We demonstrate that two commonly used anesthetic formulations differentially influence the level of vasoconstriction caused by alcohol and THC actions in cerebral arterioles.


Predictive factors for difficult intravenous cannulation in pediatric patients at a tertiary pediatric hospital.
It is generally believed that certain patient characteristics (e.g., Body Mass Index and age) predict difficulty of intravenous cannulation in children, but there is not much literature evaluating these risk factors. In this study, we investigated predictive factors for success rate at first attempt and time needed for intravenous cannulation. In a prospective cohort study, we observed characteristics of intravenous cannulations in pediatric patients at the operating room (n = 1083) and the outpatient care unit (n = 178) of a tertiary referral pediatric hospital. Time to successful intravenous cannulation, success at first attempt, and potential predictors for difficult cannulation (age, gender, skin color, BMI or weight-to-age z-score, the child being awake or anesthetized, operator profession and surgical specialty) were recorded. Regression models were constructed to find significant predictors. Success at first attempt was 73% and 81%, respectively. In the operating room age, operator and surgical specialty were predictive for a successful first attempt and time to successful cannulation. No significant predictive factors were found for the outpatient care unit. BMI or weight-to-age was not related to difficult intravenous cannulation. This study shows that in one-fifth to one-third of the patients, intravenous cannulation required more than one attempt. It is difficult to predict with accuracy the difficulty of intravenous cannulation solely with easily obtainable patient characteristics.


Current and future impact of rising multiple birth ratios on low birthweight.
Before 1980, multiple births with their increased risk of low birthweight comprised too small a proportion of births in the United States to have a significant impact on overall low birthweight levels; the recent steep rise in the multiple birth ratio has heightened their influence, however. Between 1980 and 1992 the white multiple birth ratio rose from 18.5 to 24.0 multiple births per 1,000 births. While the overall level of white low birthweight newborns increased slightly between 1980 and 1992 (from 5.7 percent to 5.8 percent), low birthweight for white singletons actually improved, declining from 4.9 to 4.7 percent. Thus, the increase in overall white low birthweight levels is a reflection of the increase in white multiple births and, to a much lesser extent, of the small increase in low birthweight among these births. Black multiple birth ratios and overall low birthweight also rose in this period. The black multiple birth ratio increased from 24.4 in 1980 to 28.2 per 1,000 births in 1992, and low birthweight rose from 12.7 to 13.3 percent. Although low birthweight for black singletons also increased (from 11.5 percent to 11.8 percent), the increase was at a slower pace than for all pluralities combined. Thus, for both white and black births, overall trends in low birthweight mask the disparate patterns of singleton and multiple births. It is, therefore, essential to examine low birthweight trends by plurality to assess accurately changes in this key indicator of infant health.


A comparison of propofol, thiopental or ketamine as induction agents in goats.
To compare propofol, thiopental and ketamine as induction agents before halothane anaesthesia in goats. Prospective, randomized cross-over study. Animals Seven healthy adult female goats with mean (+/-SD; range) body mass of 38.9 +/- 3.29 kg; 35-45 kg. The seven animals were used on 21 occasions. Each received all three anaesthetics in a randomized cross-over design, with an interval of at least 2 weeks before re-use. Anaesthesia was induced with intravenous (IV) propofol (3 mg kg(-1)), thiopental (8 mg kg(-1), IV) or ketamine (10 mg kg(-1), IV). Following tracheal intubation, anaesthesia was maintained with halothane for 30 minutes. Indirect blood pressure, heart rate, respiratory rate and arterial blood gases were monitored. The quality of induction and recovery, recovery times and incidence of side-effects were recorded. Induction of anaesthesia was smooth and uneventful, and tracheal intubation was easily performed in all but two goats receiving ketamine. Changes in cardiopulmonary variables and acid-base status were similar with all three induction agents and were within clinically acceptable limits. Mean recovery times (time to recovery of swallowing reflex and to standing) were significantly shorter, and side-effects, e.g. apnoea, regurgitation, hypersalivation and tympany, were less common in goats receiving propofol, compared with the other treatments. Propofol 3 mg kg(-1) IV is superior to thiopental and ketamine as an induction agent before halothane anaesthesia in goats. It provides uneventful recovery which is more rapid than thiopental or ketamine, so reduces anaesthetic risk.


Improving personal health records for patient-centered care.
To assess the patient-centeredness of personal health records (PHR) and offer recommendations for best practice guidelines. Semi-structured interviews were conducted in seven large early PHR adopter organizations in 2007. Organizations were purposively selected to represent a variety of US settings, including medium and large hospitals, ambulatory care facilities, insurers and health plans, government departments, and commercial sectors. Patient-centeredness was assessed against a framework of care that includes: (1) respect for patient values, preferences, and expressed needs; (2) information and education; (3) access to care; (4) emotional support to relieve fear and anxiety; (5) involvement of family and friends; (6) continuity and secure transition between healthcare providers; (7) physical comfort; (8) coordination of care. Within this framework we used evidence for patient preferences (where it exists) to compare existing PHR policies, and propose a best practice model. Most organizations enable many patient-centered functions such as data access for proxies and minors. No organization allows patient views of clinical progress notes, and turnaround times for PHR reporting of normal laboratory results can be up to 7 days. Findings suggest patient-centeredness for personal health records can be improved, and recommendations are made for best practice guidelines.


Peripheral inflammation-induced changes in songbird brain gene expression: 3' mRNA transcriptomic approach.
Species-specific neural inflammation can be induced by profound immune signalling from periphery to brain. Recent advances in transcriptomics offer cost-effective approaches to study this regulation. In a population of captive zebra finch (Taeniopygia guttata), we compare the differential gene expression patterns in lipopolysaccharide (LPS)-triggered peripheral inflammation revealed by RNA-seq and QuantSeq. The RNA-seq approach identified more differentially expressed genes but failed to detect any inflammatory markers. In contrast, QuantSeq results identified specific expression changes in the genes regulating inflammation. Next, we adopted QuantSeq to relate peripheral and brain transcriptomes. We identified subtle changes in the brain gene expression during the peripheral inflammation (e.g. up-regulation in AVD-like and ACOD1 expression) and detected co-structure between the peripheral and brain inflammation. Our results suggest benefits of the 3'end transcriptomics for association studies between peripheral and neural inflammation in genetically heterogeneous models and identify potential targets for the future brain research in birds.


Vaccination and autoimmune diseases: is prevention of adverse health effects on the horizon?
Autoimmune diseases, including multiple sclerosis and type 1 diabetes mellitus, affect about 5% of the worldwide population. In the last decade, reports have accumulated on various autoimmune disorders, such as idiopathic thrombocytopenia purpura, myopericarditis, primary ovarian failure, and systemic lupus erythematosus (SLE), following vaccination. In this review, we discuss the possible underlying mechanisms of autoimmune reactions following vaccinations and review cases of autoimmune diseases that have been correlated with vaccination. Molecular mimicry and bystander activation are reported as possible mechanisms by which vaccines can cause autoimmune reactions. The individuals who might be susceptible to develop these reactions could be especially not only those with previous post-vaccination phenomena and those with allergies but also in individuals who are prone to develop autoimmune diseases, such as those with a family history of autoimmunity or with known autoantibodies, and the genetic predisposed individuals. Further research is encouraged into the direct associations between vaccines and autoimmune conditions, and the biological mechanisms behind them.


Volume and shape in feature space on adaptive FCM in MRI segmentation.
Intensity non-uniformity (bias field) correction, contextual constraints over spatial intensity distribution and non-spherical cluster's shape in the feature space are incorporated into the fuzzy c-means (FCM) for segmentation of three-dimensional multi-spectral MR images. The bias field is modeled by a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of either intensity or membership are added into the FCM cost functions. Since the feature space is not isotropic, distance measures, other than the Euclidean distance, are used to account for the shape and volumetric effects of clusters in the feature space. The performance of segmentation is improved by combining the adaptive FCM scheme with the criteria used in Gustafson-Kessel (G-K) and Gath-Geva (G-G) algorithms through the inclusion of the cluster scatter measure. The performance of this integrated approach is quantitatively evaluated on normal MR brain images using the similarity measures. The improvement in the quality of segmentation obtained with our method is also demonstrated by comparing our results with those produced by FSL (FMRIB Software Library), a software package that is commonly used for tissue classification.


X-ray emission from SN 2012ca: A Type Ia-CSM supernova explosion in a dense surrounding medium.
X-ray emission is one of the signposts of circumstellar interaction in supernovae (SNe), but until now, it has been observed only in core-collapse SNe. The level of thermal X-ray emission is a direct measure of the density of the circumstellar medium (CSM), and the absence of X-ray emission from Type Ia SNe has been interpreted as a sign of a very low density CSM. In this paper, we report late-time (500-800 d after discovery) X-ray detections of SN 2012ca in Chandra data. The presence of hydrogen in the initial spectrum led to a classification of Type Ia-CSM, ostensibly making it the first SN Ia detected with X-rays. Our analysis of the X-ray data favours an asymmetric medium, with a high-density component which supplies the X-ray emission. The data suggest a number density >108 cm-3 in the higher density medium, which is consistent with the large observed Balmer decrement if it arises from collisional excitation. This is high compared to most core-collapse SNe, but it may be consistent with densities suggested for some Type IIn or superluminous SNe. If SN 2012ca is a thermonuclear SN, the large CSM density could imply clumps in the wind, or a dense torus or disc, consistent with the single-degenerate channel. A remote possibility for a core-degenerate channel involves a white dwarf merging with the degenerate core of an asymptotic giant branch star shortly before the explosion, leading to a common envelope around the SN.


Is the Combination of COL1A1 Gene Polymorphisms a Marker of Injury Risk?
The most commonly injured body part for skiing has been found to be the knee. The rupture of the anterior cruciate ligament (ACL) was the most frequent diagnosis. ACL ruptures are determined by several extrinsic and intrinsic risk factors including those that are hormonal, neuromuscular, anatomical, or genetic. To examine the association of both COL1A1 rs1800012 (+1245G/T) and COL1A1 rs1107946 (-1997G/T) polymorphisms, individually and as haplotypes, with ACL ruptures in recreational Polish skiers. Genomic DNA was extracted from buccal cells donated by the subjects, and genotyping was carried out using real-time polymerase chain reaction. University laboratory. 138 male recreational skiers with surgically diagnosed primary ruptures and 183 apparently healthy male recreational skiers not differing markedly in age or level of exposure to ACL injury. COL1A1 rs1800012 and COL1A1 rs1107946 polymorphisms. There were significant differences in genotype distribution of the COL1A1 rs1800012 polymorphism between the ACL rupture group and the control group. The GG homozygotes were underrepresented in the ACL rupture group compared with the control group. There were no significant differences in genotype distribution or allele frequency of COL1A1 rs1107946 polymorphisms between the ACL rupture group and the control group. The G-G (COL1A1 rs1800012G and COL1A1 rs1107946G) haplotype was the most common. There were no significant differences in haplotype distribution between the ACL-rupture and control groups. The study showed that GG homozygotes were underrepresented in the ACL-rupture group compared with the control group, which suggests an association with reduced risk of ACL injury.


Inverse correlation of population similarity and introduction date for invasive ascidians.
The genomes of many marine invertebrates, including the purple sea urchin and the solitary ascidians Ciona intestinalis and Ciona savignyi, show exceptionally high levels of heterozygosity, implying that these populations are highly polymorphic. Analysis of the C. savignyi genome found little evidence to support an elevated mutation rate, but rather points to a large population size contributing to the polymorphism level. In the present study, the relative genetic polymorphism levels in sampled populations of ten different ascidian species were determined using a similarity index generated by AFLP analysis. The goal was to determine the range of polymorphism within the populations of different species, and to uncover factors that may contribute to the high level of polymorphism. We observe that, surprisingly, the levels of polymorphism within these species show a negative correlation with the reported age of invasive populations, and that closely related species show substantially different levels of genetic polymorphism. These findings show exceptions to the assumptions that invasive species start with a low level of genetic polymorphism that increases over time and that closely related species have similar levels of genetic polymorphism.


[Post-vaccination complications during administration of BCG and BCG-M in children of Krasnodar].
Analysis of frequency and reasons of complications after BCG vaccination in 2008 - 2012 in Krasnodar Region for improvement of prevention measures. Data on frequency and structure of post-vaccination complications during vaccination against tuberculosis of Centre of Hygiene and Epidemiology in Krasnodar Region and Regional Tuberculosis Hospital in 2008 - 2012 were used. Reasons of the complications were analyzed. During the observation period 16 complications related to immunization with tuberculosis vaccine were noted with frequency index of 5.1 - 40.4 per 100 000 immunized newborns and a tendency of decrease from 2008 to 2012. In the structure of complications cold abscesses (37.5%), lymphadenitis (31.25%) and ostitis (31.25%) occurred at a similar frequency. Predominance of cold abscesses in the structure of post-vaccination complications indicates violations in vaccination technologies in maternity hospitals and children's clinics in Krasnodar city, and late periods of post-vaccination ostitis diagnostics - a decrease of epidemiologic awareness of general medical network physicians regarding BCG-vaccination complications, that requires enhancement of immunization control and requalification of personnel carrying it out.


HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus.
In the immature hippocampus, the giant depolarizing potentials (GDPs) are recurrent network-driven synaptic events generated by gamma-aminobutyric acid (GABA), which in neonatal life is depolarizing and excitatory. The GDPs enable a high degree of synchrony in immature neurons and participate in activity-dependent growth and synapse formation. To understand how human immunodeficiency virus type one (HIV-1) infection in the immature brain impairs brain growth and development, we studied the effects of HIV-1 envelope glycoprotein, gp120, a viral toxin shed in abundance by infected cells, on spontaneous occurring GDPs recorded in the CA3 pyramidal cells in neonatal (P2-P6) Sprague-Dawley rat hippocampal slices using whole-cell patch technique. Bath application of gp120 produced a sustained enhancement of GDP frequency in a concentration-dependent manner without affecting passive membrane properties, suggesting that the site of action is most likely on neural network, other than on the recorded neurons. The gp120-induced enhancement of GDPs was blocked by T140, a highly specific antagonist for the chemokine receptor, CXCR4, indicating the involvement of CXCR4 in the gp120-induced increase of GDPs. Bath application of stromal cell-derived factor-1alpha (SDF-1alpha), the only CXCR4 ligand, mimicked the effects of gp120 on GDPs, supporting the engagement of CXCR4 receptors in the gp120-induced increase of GDP occurrence. Further studies revealed the involvement of protein kinase A/C in the gp120-induced enhancement of GDPs. These results demonstrate that gp120 enhances GDPs in the neonatal rat hippocampus. This enhancement may cause an excessive increase in intracellular calcium and resultant neuronal injury, leading to retardation of the brain and behavioural development as seen in paediatric AIDS patients.


Distinct regenerative potential of trunk and appendages of Drosophila mediated by JNK signalling.
The Drosophila body comprises a central part, the trunk, and outgrowths of the trunk, the appendages. Much is known about appendage regeneration, but little about the trunk. As the wing imaginal disc contains a trunk component, the notum, and a wing appendage, we have investigated the response to ablation of these two components. We find that, in contrast with the strong regenerative response of the wing, the notum does not regenerate. Nevertheless, the elimination of the wing primordium elicits a proliferative response of notum cells, but they do not regenerate wing; they form a notum duplicate. Conversely, the wing cells cannot regenerate an ablated notum; they overproliferate and generate a hinge overgrowth. These results suggest that trunk and appendages cannot be reprogrammed to generate each other. Our experiments demonstrate that the proliferative response is mediated by JNK signalling from dying cells, but JNK functions differently in the trunk and the appendages, which may explain their distinct regenerative potential.


Effectiveness of peer education interventions for HIV prevention in developing countries: a systematic review and meta-analysis.
Peer education for HIV prevention has been widely implemented in developing countries, yet the effectiveness of this intervention has not been systematically evaluated. We conducted a systematic review and meta-analysis of peer education interventions in developing countries published between January 1990 and November 2006. Standardized methods of searching and data abstraction were utilized. Merged effect sizes were calculated using random effects models. Thirty studies were identified. In meta-analysis, peer education interventions were significantly associated with increased HIV knowledge (odds ratio [OR]: 2.28; 95%, confidence interval [CI]:1.88, 2.75), reduced equipment sharing among injection drug users (OR: 0.37; 95% CI: 0.20, 0.67), and increased condom use (OR: 1.92; 95% CI: 1.59, 2.33). Peer education programs had a nonsignificant effect on sexually transmitted infections (OR: 1.22; 95% CI:0.88, 1.71). Meta-analysis indicates that peer education programs in developing countries are moderately effective at improving behavioral outcomes but show no significant impact on biological outcomes. Further research is needed to determine factors that maximize the likelihood of program success.