A survey on the graduates from the combined emergency medicine/pediatric residency programs.
The guidelines for dual training in Emergency Medicine (EM) and Pediatrics over a 5-year program have long existed. Many have questioned the benefit of such training in relation to either specialty and in relation to Pediatric Emergency Medicine (PEM) sub-specialty training. We report on the professional outcome, career focus, and job satisfaction of these graduates. Surveys were returned from 91% (n = 29) of graduates, all of whom reported completing either of the two combined training programs. All respondents reported practicing in an emergency medicine setting either with or without an additional pediatric emphasis. Fifty-nine percent reported an academic EM affiliation. Almost all (96.5%) would choose to repeat combined training and all reported they would recommend the combined program to medical students interested in Pediatrics and EM. Combined graduates report a high level of satisfaction with their training and overwhelmingly would recommend such training to medical students. Combined graduates seem to universally work in an ED setting, although a number maintain their pediatric involvement. Over half of the graduates participate in academic EM.


Professionals' views on the roles and needs of family carers of adults with cerebral palsy and complex communication needs in hospital.
The aim of this study was to explore the views of hospital and disability service staff on the roles and needs of family carers of adults with cerebral palsy (CP) and complex communication needs (CCN) in hospital. We conducted a focus group with six hospital and disability service staff, analysed the content themes of the group discussion, and verified the analysis with participants. Participants highlighted the family carers' expertise and roles in emotional and communication support, advocacy, and providing information. They acknowledged that there is a gap between the ideal of hospital staff being able to provide all necessary care to the patient with CP, and the reality of hospital staff relying upon family carers for their expertise and provision of patient care. Hospital and disability staff do not expect family carers to replace the nurse in caring for the patient with CP and CCN in hospital. Nevertheless, family carers provide valuable support in hospital. This includes support with communication, advocacy, protection, information exchange, direct care, and emotional support. Family carers with a high level of expertise in providing care may need support in adapting to the culture of care on the ward and in transferring their roles and expertise in direct care to hospital staff. In addition, they need emotional and practical support through the stressful experience of having a family member hospitalised.


Aging of the skin: implications for cutaneous surgery.
There are precious few benefits, save perhaps experience and wisdom, that those of advanced age may claim over those who continue to dwell in their youth. One somewhat paradoxical advantage, however, is the ability of older patients to apparently heal better than younger patients after cutaneous surgery. In older patients, the incision lines are less red, the scarring is less hypertrophic, and "normalization" of appearance occurs more rapidly. And yet, the "wrapping" does not necessarily reflect the contents of the "box." Unfavorable age-dependent alterations in the physical properties of the skin and the wound-healing cascade may affect the viability and structural integrity of the postoperative result. Surgery on the aged population must therefore couple the optimism for a pleasing aesthetic result with the caution reflecting a cutaneous substrate altered by the perturbations of time. This somewhat shaky balance, although not altogether understood, is worthy of study by the physician approaching the patient of advanced age.


Analysis of the causes of pump failure and differences of failure characteristics.
It is generally accepted that sewage pumping stations are directly responsible for affecting sewer system performance in terms of combined sewer overflows and flooding. However, the specific causes of pump failure are unknown. This paper presents the analysis of pump failure data provided by four sewer management authorities in The Netherlands. Pump failures have been studied accounting for the nature of failures, operation and maintenance procedures of the management authority, ageing of the pumps and changes in the environment of pumps. Pumps have been clustered on the basis of specific characteristics of their 'environment', including pump age, operating time, pump capacity and degree of pollution of the sewage. The analysis shows that the well known 'bathtub' type failure rate curve can describe failures of sewage pumps. The impact of the degree of pollution of the sewage, however, is less clear. Operating time and total pumping capacity show no correlation with failure rate. Consequently, further research using data mining techniques is needed to separate the impact of the different aspects of the environment of a pump.


The human DINB1 gene encodes the DNA polymerase Poltheta.
The human DINB1 gene shares a high degree of homology with the Escherichia coli dinB gene. Here, we purify the hDINB1-encoded protein and show that it is a DNA polymerase. Because hDinB1 is the eighth eukaryotic DNA polymerase to be described, we have named it DNA polymerase (Pol) theta. hPoltheta is unable to bypass a cis-syn thymine-thymine dimer, nor does it bypass a (6-4) photoproduct or an abasic site. We also examine the fidelity of hPoltheta on nondamaged DNA templates by steady-state kinetic analyses and find that hPoltheta misincorporates deoxynucleotides with a frequency of about 10(-3) to 10(-4). We discuss the relationship between the fidelity of hPoltheta and its inability to bypass DNA damage.


Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder.
Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.


"Start to stop": results of a randomised controlled trial of a smoking cessation programme for teens.
To examine the feasibility, acceptability, and effectiveness of a school based smoking cessation programme among students caught smoking at school. A randomised controlled trial comparing cessation rates among students in a behavioural cessation programme and those receiving self help materials only. Eighteen schools in the Memphis, Tennessee area. Two hundred and sixty one adolescent cigarette smokers (166 male, 95 female) averaging 15.8 years of age. Students assigned to the intervention received a four session behavioural treatment programme administered individually by a health educator. In addition, these students received stage matched intervention in brief phone calls monthly until the one year follow up. Self reported and biochemically verified smoking cessation at post-test and 12 month follow up. Recruiting students who were caught smoking at school proved to be highly successful. Participants rated the programme favourably, and retention rates were high. Although treated participants improved more in tobacco related knowledge relative to controls (p = 0.002), there were no group differences in changes in attitudes toward smoking. In addition, treated and control participants demonstrated no significant differences in cessation rates both at post-test and follow up. Comparisons between self reported cessation rates and those obtained under bogus pipeline conditions or with biochemical verification suggested significant falsification of cessation among participants. Our results failed to demonstrate any significant effect of the cessation programme on smoking rates for treated adolescents compared with controls. Our findings also highlight the importance of utilising strong methodology in research on adolescent smoking cessation, including control groups and biochemical verification of smoking status.


Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.
Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.


Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly.
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, camptodactyly, contrature of major joints, scoliosis, pectus deformities, and crumpled ears. The present study aimed to identify the genetic cause of a three-generation Chinese family with CCA. We successfully identified a novel missense mutation p.G1145D in the fibrillin-2 (FBN2) gene as the pathogenic mutation by whole exome sequencing (WES). The p.G1145D mutation occurs in the 12th calcium-binding epidermal growth factor-like (cbEGF) domain. The p.G1145D mutation caused a hydrophobic to hydrophilic substitution, altering the amino acid property from neutral to acidic. Three-dimensional structural analysis showed that this mutation could alter the conformation of the residue side chain, thereby producing steric clashes with spatially adjacent residues, disrupting the formation of H bonds and causing folding destabilization. Therefore, this amino acid appears to play an important role in the structure and function of FBN2. Our results may also provide new insights into the cause and diagnosis of CCA and may have implications for genetic counseling and clinical management.


Nucleotide/Tb3+ coordination polymer as a luminescent nanosensor: synthesis and sensing of iron(ii) in human serum.
Metal organic coordination polymers have emerged as a new class of functional nanomaterials because of their flexible components and diverse architecture. Here, we report the synthesis of a luminescent sensing nucleotide/Tb3+ coordination polymer by the self-assembly of a biomolecule nucleotide, a lanthanide ion and a functional ligand 1,10-phenanthroline. Due to the incorporation of 1,10-phenanthroline as both a sensitizer and a recognition unit, the luminescence of this coordination polymer was enhanced 32 times, and exhibited excellent selectivity and sensitivity to the iron(ii) ions. This coordination polymer containing Tb3+ ions has a long luminescence lifetime of up to a millisecond, and was applied to detect Fe2+ ions in human serum by time-resolved fluorimetry. The detection limit is as low as 30 nM. The results demonstrate that metal organic coordination polymers have great potential in constructing specific nanosensors through their components and structural flexibility, and could provide new chemical sensing methods for ions/molecules.


Piezoelectric Smart Patch Operated with Machine-Learning Algorithms for Effective Detection and Elimination of Condensation.
Timely detection and elimination of surface condensation is crucial for diverse applications in agriculture, automotive, oil and gas industries, and respiratory monitoring. In this paper, a smart patch based on a ZnO/aluminum (∼5 μm/50 μm thick) flexible Lamb wave device has been proposed to detect, prevent, and eliminate condensation, which can be realized using both of its surfaces. The patch is operated using a machine-learning algorithm which consists of data preprocessing (feature selection and optimization) and model training by a random forest algorithm. It has been tested in six cases, and the results show good detection performance with average precision = 94.40% and average F1 score = 93.23%. The principle of accelerating evaporation is investigated to understand the elimination and prevention functions for surface condensation. Results show that both dielectric heating and acoustothermal effect have their contributions, whereas the former is found more dominant. Furthermore, the functional relationship between the evaporation rate and the input power is calibrated, showing a high linearity (R2 = 97.64%) with a slope of ∼3.6 × 10-5 1/(s·mW). With an input power of ∼0.6 W, the flexible device has been proven effective in the prevention of condensation.


Is the gravity effect of radiographic anatomic features enough to justify stone clearance or fragments retention following extracorporeal shock wave lithotripsy (SWL).
We determined whether the gravity effect of radiographic anatomic features on the preoperative urography (IVP) are enough to predict fragments clearance after shock wave lithotripsy (SWL). A Total of 282 patients with mean age 45.8 ± 13.2 years (189 male, 93 female), who underwent SWL due to renal calculi between October 2005 and August 2009 were enrolled. The mean calculi load was 155.72 ± 127.66 mm². The patients were stratified into three groups: patients with pelvis calculi (group 1); patients with upper or middle pole calculi (group 2) and patients with lower pole calculi (group 3). Three angles on the pretreatment IVP were measured: the inner angle between the axis of the lower pole infundibular and ureteropelvic axis (angle I); the inner angle between the lower pole infundibular axis and main axis of pelvis-ureteropelvic (UP) junction point (angle II) and the inner angle between the lower pole infundibular axis and perpendicular line (angle III). Multivariate analysis was used to define the significant predictors of stone clearance. The overall success rate was 85.81%. All angles, sessions number, shock waves number and stone burden were significant predictors of success in patients in group 1. However, in group 2 only angle II and in group 3 angles I and II had significant effect on stone clearance. Radiographic anatomic features have significant role in determining the stone-free rate following satisfactory fragmentation of renal stones with SWL. The measurement of infundibulopelvic angle in different manner helps to predict the stone-free status in patients with renal calculi located not only in lower pole, but also in renal pelvis and upper or middle pole. Gravity effect is not enough to justify the significant influence of the radiographic anatomic features on the stone clearance and fragments retention after SWL.


Role of environmental variability in the evolution of life history strategies.
We reexamine the role of environmental variability in the evolution of life history strategies. We show that normally distributed deviations in the quality of the environment should lead to normally distributed deviations in the logarithm of year-to-year survival probabilities, which leads to interesting consequences for the evolution of annual and perennial strategies and reproductive effort. We also examine the effects of using differing criteria to determine the outcome of selection. Some predictions of previous theory are reversed, allowing distinctions between r and K theory and a theory based on variability. However, these distinctions require information about both the environment and the selection process not required by current theory.


Studies on degradation of glyphosate by several oxidative chemical processes: ozonation, photolysis and heterogeneous photocatalysis.
Several different Advanced Oxidation Processes (AOPs) including ozonation at pH 6.5 and 10, photolysis and heterogeneous photocatalysis using TiO(2) as semiconductor and dissolved oxygen as electron acceptor were applied to study the degradation of glyphosate (N-phosphonomethyl glycine) in water. The degree of glyphosate degradation, the reactions kinetic and the formation of the major metabolite, aminomethyl phosphonic acid (AMPA), were evaluated. Ozonation at pH 10 resulted in the maximum mineralization of glyphosate. It was observed that under the experimental conditions used in this study the degradation of glyphosate followed the first-order kinetics. The half-life obtained for glyphosate degradation in the O(3)/pH 10 process was 1.8 minutes.


Kinetically-derived maximal dose (KMD) indicates lack of human carcinogenicity of ethylbenzene.
The kinetically-derived maximal dose (KMD) is defined as the maximal external dose at which kinetics are unchanged relative to lower doses, e.g., doses at which kinetic processes are not saturated. Toxicity produced at doses above the KMD can be qualitatively different from toxicity produced at lower doses. Here, we test the hypothesis that neoplastic lesions reported in the National Toxicology Program's (NTP) rodent cancer bioassay with ethylbenzene are a high-dose phenomenon secondary to saturation of elimination kinetics. To test this, we applied Bayesian modeling on kinetic data for ethylbenzene from rats and humans to estimate the Vmax and Km for the Michaelis-Menten equation that governs the elimination kinetics. Analysis of the Michaelis-Menten elimination curve generated from those Vmax and Km values indicated KMD ranges for venous ethylbenzene of 8-17 mg/L in rats and 10-18 mg/L in humans. Those venous concentrations are produced by inhalation concentrations of around 200 ppm ethylbenzene, which is well above typical human exposures. These KMD estimates support the hypothesis that neoplastic lesions seen in the NTP rodent bioassay occur secondary to saturation of ethylbenzene elimination pathways and are not relevant for human risk assessment. Thus, ethylbenzene does not pose a credible cancer risk to humans under foreseeable exposure conditions. Cancer risk assessments focused on protecting human health should avoid endpoint data from rodents exposed to ethylbenzene above the KMD range and future toxicological testing should focus on doses below the KMD range.


Designing deep sequencing experiments: detecting structural variation and estimating transcript abundance.
Massively parallel DNA sequencing technologies have enabled the sequencing of several individual human genomes. These technologies are also being used in novel ways for mRNA expression profiling, genome-wide discovery of transcription-factor binding sites, small RNA discovery, etc. The multitude of sequencing platforms, each with their unique characteristics, pose a number of design challenges, regarding the technology to be used and the depth of sequencing required for a particular sequencing application. Here we describe a number of analytical and empirical results to address design questions for two applications: detection of structural variations from paired-end sequencing and estimating mRNA transcript abundance. For structural variation, our results provide explicit trade-offs between the detection and resolution of rearrangement breakpoints, and the optimal mix of paired-read insert lengths. Specifically, we prove that optimal detection and resolution of breakpoints is achieved using a mix of exactly two insert library lengths. Furthermore, we derive explicit formulae to determine these insert length combinations, enabling a 15% improvement in breakpoint detection at the same experimental cost. On empirical short read data, these predictions show good concordance with Illumina 200 bp and 2 Kbp insert length libraries. For transcriptome sequencing, we determine the sequencing depth needed to detect rare transcripts from a small pilot study. With only 1 Million reads, we derive corrections that enable almost perfect prediction of the underlying expression probability distribution, and use this to predict the sequencing depth required to detect low expressed genes with greater than 95% probability. Together, our results form a generic framework for many design considerations related to high-throughput sequencing. We provide software tools http://bix.ucsd.edu/projects/NGS-DesignTools to derive platform independent guidelines for designing sequencing experiments (amount of sequencing, choice of insert length, mix of libraries) for novel applications of next generation sequencing.


Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism.
Heterozygous mutations in the gene for the Kit transmembrane receptor have been identified recently in human piebaldism and mouse "dominant spotting." Interestingly, all of the 14 known missense mutations that cause depigmentation in these species map to the tyrosine kinase domain of the receptor, whereas none have involved the extracellular ligand-binding domain. In an attempt to detect these uncommon mutations, we screened the nine exons encoding the extracellular portion of Kit for single-strand conformation polymorphisms (SSCP) in eight piebald subjects previously reported to be negative for kinase mutations. Four of these eight kindreds proved to carry novel mutations. The first mutation, found in two apparently unrelated probands with mild piebaldism and English ancestry, substitutes an arginine for a highly conserved cysteine at codon 136. This substitution disrupts a putative disulfide bond required for formation of the second Ig-like (D2) loop of the Kit ligand-binding domain. The second mutation, detected in a piebald kindred characterized by unusually limited depigmentation, substitutes a threonine for an alanine at codon 178, a site just proximal to conserved cysteines at codons 183 and 186. The third mutation, occurring in a kindred with more extensive depigmentation, is a novel four-base insertion in exon 2 that results in a proximal frameshift and premature termination. The data strongly suggest that piebaldism can result from missense mutations in the Kit ligand-binding domain, although the resulting phenotype may be milder than that observed for null or kinase mutations. The apparent clustering of these uncommon mutations at or near the conserved cysteines for the D2 Ig-like loop further suggests a critical role for this region in Kit receptor function.


Efficient purification of CD4+ lymphocytes from peripheral blood progenitor cell products using affinity bead acoustophoresis.
Processing of peripheral blood progenitor cells (PBPC) for clinical transplantation or research applications aims to effectively isolate or deplete specific cell populations, utilizing primarily magnetic or fluorescence activated sorting methods. Here, we investigated the performance of microfluidic acoustophoresis for the separation of lymphocyte subsets from PBPC, and present a novel method for affinity-bead-mediated acoustic separation of cells which can otherwise not be acoustically discriminated. As the acoustic force on a particle depends on particle size, density and compressibility, targeting of cells by affinity specific beads will generate cell-bead complexes that exhibit distinct acoustic properties relative to nontargeted cells and are, thus, possible to isolate. To demonstrate this, PBPC samples (n = 22) were obtained from patients and healthy donors. Following density gradient centrifugation, cells were labeled with anti-CD4-coated magnetic beads (Dynal) and isolated by acoustophoresis and, for comparison, standard magnetic cell sorting technique in parallel. Targeted CD4+ lymphocytes were acoustically isolated with a mean (±SD) purity of 87 ± 12%, compared with 96 ± 3% for control magnetic sorting. Viability of sorted cells was 95 ± 4% (acoustic) and 97 ± 3% (magnetic), respectively. The mean acoustic separation efficiency of CD4+ lymphocytes to the target fraction was 65 ± 22%, compared with a mean CD4+ lymphocyte recovery of 56 ± 15% for magnetic sorting. Functional testing of targeted CD4+ lymphocytes demonstrated unimpaired mitogen-mediated proliferation capacity and cytokine production. Hematopoietic progenitor cell assays revealed a preserved colony forming ability of nontarget cells post sorting. We conclude that the acoustophoresis platform can be utilized to efficiently isolate bead-labeled CD4+ lymphocytes from PBPC samples in a continuous flow format, with preserved functional capacity of both target and nontarget cells. These results open up for simultaneous affinity-bead-mediated separation of multiple cell populations, something which is not possible with current standard magnetic cell separation technology. © 2014 International Society for Advancement of Cytometry.


The evolution of transgenerational integration of information in heterogeneous environments.
An organism's phenotype can be influenced by maternal cues and directly perceived environmental cues, as well as by its genotype at polymorphic loci, which can be interpreted as a genetic cue. In fluctuating environments, natural selection favors organisms that efficiently integrate different sources of information about the likely success of phenotypic alternatives. In such situations, it can be beneficial to pass on maternal cues that offspring can respond to. A maternal cue could be based on environmental cues directly perceived by the mother but also partly on cues that were passed on by the grandmother. We have used a mathematical model to investigate how the passing of maternal cues and the integration of different sources of information evolve in response to qualitatively different kinds of temporal and spatial environmental fluctuations. The model shows that the passing of maternal cues and the transgenerational integration of sources of information readily evolve. Factors such as the degree of temporal autocorrelation, the predictive accuracy of different environmental cues, and the level of gene flow strongly influence the expression of adaptive maternal cues and the relative weights given to different sources of information. We outline the main features of the relation between the characteristics of environmental fluctuations and the adaptive systems of phenotype determination and compare these predictions with empirical studies on cue integration.


Early intrauterine development: I. The rate of growth of Caucasian embryos and fetuses between the 6th and 20th weeks of gestation.
Liberalization of abortion laws in various countries and states of Europe and America has offered an opportunity for the study of the correlations between menstrual age and the rate of bodily development of human embryos and fetuses. In several institutions where local bylaws mandated the consent of the patients requesting therapeutic abortion to pathological investigation of the products of conception, various parameters of growth were measured systematically. These included crown-rump and foot lengths and body weight. The analysis of the data indicated that in the embryosic stages of development the rate of growth is substantially slower than it had been assumed previously. In the more advanced fetal stages of development the findings supported the validity of the long-established standard of Streeter. Since the current study has been based on apparently normal gestations of healthy women, whereas earlier data had rested, to a great extent, on spontaneously aborted and extopic embryon and fetuses, it seems evident that pathological specimens are not suitable for the purpose of establishing reliable standards of normal intrauterine growth rate. The present data support the suggestion, based on various experimental and clinical observations, that pathological gestations often result from abnormal ovulations that occur at times other than the mid-cycle and that such conceptions are frequently followed by a bleeding episode that simulates menstruation. It is likely that the inclusion of a high number of such cases biased the results of earlier investigations concerning embryonic growth rate on account of the frequent incidence of erroneous menstrual histories. The material available did not permit the extension of the investigation beyond the 20th week of gestation. It appears, however, that the average growth rate in the mid-trimester may be slower than the data adopted by the American Academy of Pediatrics would indicate. The possible causes of some phenomena observed in the course of the investigation, such as unexplained scatter of growth-rate patterns at all developmental stages and discrepancies among various literary data, have been discussed in some detail. While a tentative attempt has been made to correlate the investigated parameters of fetal growth with biparietal diameters of the head, a measurement accessible to direct assessment by sonography during pregnancy, the necessity of improving these standards through a prospective study has been emphasized.


Evidence for the impact of quality improvement collaboratives: systematic review.
To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives.


Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies.
The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT's myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it.


Clinical evaluation of a commercial orthopedic metal artifact reduction tool for CT simulations in radiation therapy.
Severe artifacts in kilovoltage-CT simulation images caused by large metallic implants can significantly degrade the conspicuity and apparent CT Hounsfield number of targets and anatomic structures, jeopardize the confidence of anatomical segmentation, and introduce inaccuracies into the radiation therapy treatment planning process. This study evaluated the performance of the first commercial orthopedic metal artifact reduction function (O-MAR) for radiation therapy, and investigated its clinical applications in treatment planning. Both phantom and clinical data were used for the evaluation. The CIRS electron density phantom with known physical (and electron) density plugs and removable titanium implants was scanned on a Philips Brilliance Big Bore 16-slice CT simulator. The CT Hounsfield numbers of density plugs on both uncorrected and O-MAR corrected images were compared. Treatment planning accuracy was evaluated by comparing simulated dose distributions computed using the true density images, uncorrected images, and O-MAR corrected images. Ten CT image sets of patients with large hip implants were processed with the O-MAR function and evaluated by two radiation oncologists using a five-point score for overall image quality, anatomical conspicuity, and CT Hounsfield number accuracy. By utilizing the same structure contours delineated from the O-MAR corrected images, clinical IMRT treatment plans for five patients were computed on the uncorrected and O-MAR corrected images, respectively, and compared. Results of the phantom study indicated that CT Hounsfield number accuracy and noise were improved on the O-MAR corrected images, especially for images with bilateral metal implants. The γ pass rates of the simulated dose distributions computed on the uncorrected and O-MAR corrected images referenced to those of the true densities were higher than 99.9% (even when using 1% and 3 mm distance-to-agreement criterion), suggesting that dose distributions were clinically identical. In all patient cases, radiation oncologists rated O-MAR corrected images as higher quality. Formerly obscured critical structures were able to be visualized. The overall image quality and the conspicuity in critical organs were significantly improved compared with the uncorrected images: overall quality score (1.35 vs 3.25, P = 0.0022); bladder (2.15 vs 3.7, P = 0.0023); prostate and seminal vesicles∕vagina (1.3 vs 3.275, P = 0.0020); rectum (2.8 vs 3.9, P = 0.0021). The noise levels of the selected ROIs were reduced from 93.7 to 38.2 HU. On most cases (8∕10), the average CT Hounsfield numbers of the prostate∕vagina on the O-MAR corrected images were closer to the referenced value (41.2 HU, an average measured from patients without metal implants) than those on the uncorrected images. High γ pass rates of the five IMRT dose distribution pairs indicated that the dose distributions were not significantly affected by the CT image improvements. Overall, this study indicated that the O-MAR function can remarkably reduce metal artifacts and improve both CT Hounsfield number accuracy and target and critical structure visualization. Although there was no significant impact of the O-MAR algorithm on the calculated dose distributions, we suggest that O-MAR corrected images are more suitable for the entire treatment planning process by offering better anatomical structure visualization, improving radiation oncologists' confidence in target delineation, and by avoiding subjective density overrides of artifact regions on uncorrected images.


Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States.
How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA. Experimental and epidemiological studies published in 1963-2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting.Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases.Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco.Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries.Oral pain: Limited evidence precludes any clear conclusion. This review confirms the strong association of current use of smokeless tobacco, particularly snuff, with prevalence of oral mucosal lesions. It provides suggestive evidence of an association of snuff use with gingival recession and attachment loss, and of chewing tobacco with dental caries. While smokeless tobacco clearly increases risk of oral mucosal lesions, interpretation for other endpoints is limited by study weaknesses, including poor confounding control.


Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction.
Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.


Laparoscopic removal of a paracaval air gun bullet in a child.
Air guns are known as low-velocity arms and are considered harmless. However, injuries from air weapons can be serious and even fatal, particularly in children. We present a potentially life-threatening penetrating retroperitoneal injury of a 3-year-old boy caused by an air gun, and the successful removal of the bullet via a laparoscopic approach. The patient was brought to our center with a penetrating air gunshot wound on his right side in the waist area. He was accidentally shot by his brother at their home. The patient's clinical condition was stable. Computed tomography scan showed the bullet in the retroperitoneum near the inferior vena cava. A three-port laparoscopic transperitoneal approach was performed. The bullet was found just 0.5 cm caudal to the right renal hilum and 0.5 cm near the inferior vena cava; it was then removed. Operation time was 42 min and the postoperative course was uneventful. Thanks to improvements in laparoscopic surgical techniques, laparoscopy has become a feasible and effective treatment modality even for the removal of foreign bodies in children.


Global Odds Model with Proportional Odds and Trend Odds Applied to Gross and Microscopic Brain Infarcts.
Medical and epidemiological researchers commonly study ordinal measures of symptoms or pathology. Some of these studies involve two correlated ordinal measures. There is often an interest in including both measures in the modeling. It is common to see analyses that consider one of the measures as a predictor in the model for the other measure as outcome. There are, however, issues with these analyses including biased estimate of the probabilities and a decreased power due to multicollinearity (since they share some predictors). These issues create a necessity to examine both variables as simultaneous outcomes, by assessing the marginal probabilities for each outcome (i.e. using a proportional odds model) and the association between the two outcomes (i.e. using a constant global odds model). In this work we extend this model using a parsimonious option when the constraints imposed by assumptions of proportional marginal odds and constant global odds do not hold. We compare approaches by using simulations and by analyzing data on brain infarcts in older adults. Age at death is a marginal predictor of gross infarcts and also a marginal predictor of microscopic infarcts, but does not modify the association between gross and microscopic infarcts.


Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer.
Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a "liquid biopsy" for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC. Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis. A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P<0.001), and Ki-67 level (r=0.510, P=0.005). When compared to the traditional methods, monitoring CTC subtypes exhibits higher sensitivity of evaluating the disease status. Enumeration of epithelial CTC subset and its relative abundance in the total CTC pool are highly correlated with clinical efficacy. CTC programmed cell death ligand-1 (PD-L1) could be successfully detected for immunotherapy in addition to PD-L1 immunohistochemistry and microsatellite instability. We provide a new method that allows for the simple and effective detection of CTCs in aGC. It has potential clinical applications in monitoring prognosis and guiding future individualized immunotherapy.


Staphylococcus aureus meningitis. A review of 104 nationwide, consecutive cases.
Based on a nationwide registration, the clinical and bacteriologic data from 61 postoperative and 43 hematogenous cases of Staphylococcus aureus meningitis in Denmark from 1986 through 1989 were reviewed. Postoperative meningitis was a foreign body infection in 89% of the cases and had a lower mortality (18% [11/61]) compared with hematogenous meningitis (56% [24/43]). Hematogenous S aureus meningitis seems to be part of an overwhelming, disseminated infection as indicated by the following: 81% of the patients had bacteremia, 21% had endocarditis, and 12% had osteomyelitis. Most patients were older, often with underlying diseases, community-acquired infections, and a clinical picture of severe meningitis. The major findings were mental status changes and a high rate (34%) of focal neurological changes. The initial leukocyte count in the cerebrospinal fluid sample was low, and the bacteria were seen in Gram's stain smears in 40% of cases only. The prognosis was related to the age of the patients and the initial antibiotic treatment. Patients treated with penicillinase-stable penicillins in combination with fusidic acid may have a better prognosis. Three (12%) of 25 surviving patients had severe sequelae. Hematogenous S aureus meningitis is a severe disease with a high mortality related to age, presence of shock, and infection with strains of phage type 95.


Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males.
Females in various species typically avoid males infected with parasites, while parasite-free males advertise their status through conspicuous phenotypic traits. This process selects for heritable resistance and reduces direct exposure of the female to parasites. Coevolving parasites are likely to attempt to circumvent this obstacle. In this paper, we demonstrate a case of parasitic manipulation of host mate choice. We report that Toxoplasma gondii, a sexually transmitted infection of brown rats, enhances sexual attractiveness of infected males. Thus under some evolutionary niches, parasites can indeed manipulate host sexual signaling to their own advantage.


High-fidelity in vivo replication of DNA base shape mimics without Watson-Crick hydrogen bonds.
We report studies testing the importance of Watson-Crick hydrogen bonding, base-pair geometry, and steric effects during DNA replication in living bacterial cells. Nonpolar DNA base shape mimics of thymine and adenine (abbreviated F and Q, respectively) were introduced into Escherichia coli by insertion into a phage genome followed by transfection of the vector into bacteria. Genetic assays showed that these two base mimics were bypassed with moderate to high efficiency in the cells and with very high efficiency under damage-response (SOS induction) conditions. Under both sets of conditions, the T-shape mimic (F) encoded genetic information in the bacteria as if it were thymine, directing incorporation of adenine opposite it with high fidelity. Similarly, the A mimic (Q) directed incorporation of thymine opposite itself with high fidelity. The data establish that Watson-Crick hydrogen bonding is not necessary for high-fidelity replication of a base pair in vivo. The results suggest that recognition of DNA base shape alone serves as the most powerful determinant of fidelity during transfer of genetic information in a living organism.


Treatment Patterns for Myopic Choroidal Neovascularization in the United States: Analysis of the IRIS Registry.
To characterize treatment patterns and outcomes in eyes with treatment-naïve myopic choroidal neovascularization (mCNV) in the United States. Retrospective cohort study. Individuals aged 18 years and older seen in clinics participating in the American Academy of Ophthalmology's IRIS (Intelligent Research in Sight) Registry. We analyzed data from the IRIS Registry, from January 1, 2012 to December 31, 2014, to identify cases of treatment-naïve mCNV, which was defined as the presence of myopic refractive error worse than -6.0 diopters with the presence of subretinal/choroidal neovascularization as indicated by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of "362.16: Retinal Neovascularization NOS." Type of initial treatment for mCNV was categorized as the administration of 1 of the following within the first 365 days after the diagnosis date: (1) observation (i.e., no treatment); (2) intravitreal anti-VEGF injection; (3) verteporfin photodynamic therapy (vPDT); or (4) laser photocoagulation. We assessed the difference between logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) on the diagnosis date (baseline) and 1 year after the diagnosis date. Anti-VEGF injection frequency per treated eye over a 1-year period was also estimated. We identified 185 patients with treatment-naïve mCNV in 1 or both eyes. Treatment within 1 year of diagnosis was recorded for 73.0% (135/185); the remainder was classified as "observation." Nearly all treatment (134/135; 99.3%) consisted of anti-VEGF injections; 0.7% (1/135) received vPDT. Those treated with anti-VEGF injections showed significant improvement in VA at 1 year (mean logMAR VA improvement of 0.17 units, 95% confidence interval [CI], 0.12-0.20, P < 0.01), whereas those who were not treated showed a significant decline in VA at 1 year (mean logMAR VA decline: 0.03 units, 95% CI, 0.008-0.05, P < 0.01). The mean number of anti-VEGF injections for an eye with mCNV during the first year after diagnosis was 2.8 (standard deviation, 2.5) (median, 2.0; interquartile range, 1.0-4.0). In the United States, anti-VEGF injection was the most frequently utilized treatment for mCNV. Those treated were observed to gain vision. However, one quarter of patients received no treatment and lost vision. Further studies are needed to understand the sociodemographic and health-systems barriers surrounding the delivery of anti-VEGF injections to patients with mCNV.


Diagnosis, surgical treatment, and performance after unilateral castration in breeding bulls: 21 cases (1989-1999).
To evaluate signalment, surgical treatment, postoperative complications, and future breeding success or semen production in a group of bulls with naturally occurring disease of the scrotum or testis. Retrospective study. 21 bulls that underwent unilateral castration after evaluation for scrotal swelling. A computer-assisted search of medical records at 2 veterinary teaching hospitals was performed. Historical, diagnostic, surgical, and follow-up data were collected and analyzed for those bulls with scrotal swelling that underwent unilateral castration. Four of 5 pasture breeding bulls and 9 of 10 semen collection-center bulls successfully bred cows or produced viable semen within 6 months of surgery. Fourteen of 21 surgical procedures were performed after induction of general anesthesia. Sixty-six percent of procedures were performed as open castrations. Seventy-one percent of bulls developed postoperative complications, most of which were mild swellings. Unilateral castration returned 13 of 15 bulls with unilateral disease of the scrotum or testis to productive service by 6 months after surgery. Unilateral castration is an effective treatment for unilateral disease of the,scrotum or testis in bulls, allowing return to reproductive function.


Medroxyprogesterone effects on colony growth, autophagy and mitochondria of C6 glioma cells are augmented with tibolone and temozolomide: Cell kinetic and electron microscopical studies with a broad review of the literature.
Risk of high grade gliomas is lower in young females and its incidence enhances after menopause suggesting likely protective roles of female hormones. Hormone replacement therapy (HRT) was widely employed to treat osteoporosis and some epidemiological studies showed that HRT regimes including progesterone analogs such as medroxyprogesterone acetate (MPA) decreased risk of glial tumors. Tibolone is a unique progesterone analog employed in HRT with tissue specific estrogenic effects and stimulates gene expressions very similar to those induced by MPA. Tibolone's pro-estrogenic effects occur particularly in bone and brain and both MPA and tibolone inhibit AKR1C enzymes, which involve in temozolomide chemoresistance. Hence, we aimed to investigate interactions between MPA, tibolone and temozolomide in modification of glioma cell growth and fine structure. For our studies, we have particularly chosen C6 rat glioma cell line due to several reasons: i) We previously showed that MPA reduced growth and induced procarbazine-sensitization in C6 cells; ii) temozolomide has a triazene-type molecular structure like procarbazine; iii) other groups previously showed that C6 glioma cell line is more resistant to temozolomide than human glioma cells; hence it may provide a native model of chemoresistance. Monolayer plating efficacy, soft agar colony growth, 3D-spheroid S-phase (as determined by BrdU-labeling) and electron microscopical analyses were performed to assess mutual interactions between MPA, tibolone and temozolomide. MPA inhibited clonogenic growth of C6 glioma and this effect is augmented by both tibolone and temozolomide. MPA and tibolone inhibited DNA synthesis in C6 glioma spheroids to similar levels which can be achieved with temozolomide. Electron microscopical analyses revealed synergisms between MPA, tibolone and temozolomide involved mitochondrial proliferation, condensation, mitophagy and autophagy. MPA and tibolone shall be studied in further experimental models of glioblastoma in vitro and in vivo.


Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene.
Generalized progressive retinal atrophy (gPRA) belongs to a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, including the Irish Glen of Imaal Terrier (GIT). By genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions, we assigned the gPRA candidate locus in this breed to canine chromosome 16. The respective region is syntenic with human chromosome 8 comprising the ADAM metallopeptidase domain 9 (ADAM9) gene. ADAM9 represents a strong candidate gene for canine retinal disease because mutations have previously been shown to cause autosomal recessively inherited human cone-rod dystrophy, a retinal disorder affecting photoreceptor function. Sequence analysis of ADAM9 in affected and carrier GITs revealed a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon. This mutation was absent from 34 other dog breeds. A variable and, at times, very late onset of gPRA was confirmed in GITs by a relatively mild retinal degeneration at an advanced age. Hence, the identification of the genetic defect underlying gPRA in the GIT represents a suitable model for cone-rod dystrophy of humans, with superior potential to elucidate functional consequences of the recently described null mutations in the human ADAM9 gene.


[Divergence of unique DNA sequences of bivalve mollusks from Mytilinae subfamily (Bivalvia mytilidae)].
The DNA-DNA hybridization method was used to determine the divergence degree of unique sequences of five bivalvia species belonging to the Mytilinae subfamily. The matrix of delta Tm values for heteroduplexes of unique sequences was found which made it possible to define three phylogenetic branches within the subfamily. Under non-stringent hybridization conditions (55 degrees C, 0.5M PB) the divergence between species of any two branches was about 14% of nucleotide substitutions. The hybridization of [3H] unique sequences of Mytilinae with DNA fragments of Modiolus modiolus, a representative of the closest relative Modiolinae subfamily, showed that the divergence rate of unique sequences in two phylogenetic lines of the Mytilus genusis higher than in the line of the Crenomytilus genus I0.35-0.23% and 0.1% of nucleotide substitutions per one million years, respectively). According to the matrix of delta Tm values for five species of Mytilinae and Modiolus modiolus, a phylogenetic tree was built reflecting the differences between the divergence rates in different branches.


Correlation between proteinuria level and renal morphology with special reference to electron microscopy in kidney donors.
The aims of this study were to evaluate whether there is a correlation between protein level in urine and renal morphology in kidney transplant donors, as well as to detect the role of electron microscopy. For this purpose, kidney biopsies of 10 donors with urine protein levels were evaluated. Seven patients were female and three were male. Two had physiologic proteinuria (< 150 mg/24h), four had non-significant proteinuria (150-300 mg/24h), and three had significant (> 300 mg/24h) proteinuria. Serum creatinine levels were in normal ranges in all patients except for one who had a slight increase (1.76 mg/dL). Seven cases were reported to have normal or nonspecific light microscopic findings. Two of those seven cases had physiologic proteinuria, three had non-significant proteinuria, and two had significant proteinuria. One case had IgA nephropathy with significant proteinuria. One donor had early stage focal segmental glomerulosclerosis with non-significant proteinuria, and one donor had focal interstitial fibrosis with normal urine protein level. There was no statistically significant difference between score means of ultrastructural morphology of the six patients with same patients' light microscopic results and score means of light microscopic results with urine protein levels of all patients. However, there was a significant difference between score means of ultrastructural morphology with urine protein levels of those six patients. In conclusion, urine protein levels and light microscopic findings did not always reflect the detailed morphology alone and together. Therefore, combining with electron microscopic examination could be more beneficial in relieving problems occurring in long-term prognoses.


Community-based participatory research and policy advocacy to reduce diesel exposure in West Oakland, California.
We conducted a multimethod case study analysis of a community-based participatory research partnership in West Oakland, California, and its efforts to study and address the neighborhood's disproportionate exposure to diesel air pollution. We employed 10 interviews with partners and policymakers, participant observation, and a review of documents. Results of the partnership's truck count and truck idling studies suggested substantial exposure to diesel pollution and were used by the partners and their allies to make the case for a truck route ordinance. Despite weak enforcement, the partnership's increased political visibility helped change the policy environment, with the community partner now heavily engaged in environmental decision-making on the local and regional levels. Finally, we discussed implications for research, policy, and practice.


Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors.
Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach.


Functional characterization of alanine racemase from Schizosaccharomyces pombe: a eucaryotic counterpart to bacterial alanine racemase.
Schizosaccharomyces pombe has an open reading frame, which we named alr1(+), encoding a putative protein similar to bacterial alanine racemase. We cloned the alr1(+) gene in Escherichia coli and purified the gene product (Alr1p), with an M(r) of 41,590, to homogeneity. Alr1p contains pyridoxal 5'-phosphate as a coenzyme and catalyzes the racemization of alanine with apparent K(m) and V(max) values as follows: for L-alanine, 5.0 mM and 670 micromol/min/mg, respectively, and for D-alanine, 2.4 mM and 350 micromol/min/mg, respectively. The enzyme is almost specific to alanine, but L-serine and L-2-aminobutyrate are racemized slowly at rates 3.7 and 0.37% of that of L-alanine, respectively. S. pombe uses D-alanine as a sole nitrogen source, but deletion of the alr1(+) gene resulted in retarded growth on the same medium. This indicates that S. pombe has catabolic pathways for both enantiomers of alanine and that the pathway for L-alanine coupled with racemization plays a major role in the catabolism of D-alanine. Saccharomyces cerevisiae differs markedly from S. pombe: S. cerevisiae uses L-alanine but not D-alanine as a sole nitrogen source. Moreover, D-alanine is toxic to S. cerevisiae. However, heterologous expression of the alr1(+) gene enabled S. cerevisiae to grow efficiently on D-alanine as a sole nitrogen source. The recombinant yeast was relieved from the toxicity of D-alanine.


Clinical significance of cumulative biological effective dose and overall treatment time in the treatment of carcinoma cervix.
The purpose of this retrospective study is to report the radiotherapy treatment response of, and complications in, patients with cervical cancer on the basis of cumulative biologic effective dose (BED) and overall treatment time (OTT).Sixty-four (stage II - 35/64; stage III - 29/64) patients of cervical cancer were treated with combination of external beam radiotherapy (EBRT) and low dose rate intracavitary brachytherapy (ICBT). The cumulative BED was calculated at Point A (BED(10)); and bladder, rectal reference points (BED(2,5)) using the linear-quadratic BED equations.The local control (LC) rate and 5-year disease-free survival (DFS) rate in patients of stage II were comparable for BED(10) <84.5 and BED(10) >84.5 but were much higher for BED(10) >84.5 than BED(10) <84.5 (P< 0.01) in stage III patients. In the stage II patients, The LC rate and 5-year DFS rate were comparable for OTT <50 days and for OTT >50 days but were much higher in stage III patients with OTT < 50 than OTT >50 days (P< 0.001). It was also observed that patients who received BED(2.5) <105 had lesser rectal (P< 0.001) and bladder complications than BED(2.5) >105. Higher rectal complication-free survival (CFS(R)) rate, bladder complication-free survival (CFS(B)) rate and all-type late complication-free survival rate were observed in patients who received BED(2.5) < 105 than BED(2.5) >105.A balanced, optimal and justified radiotherapy treatment schedule to deliver higher BED(10) (>84.5) and lower BED(2.5) (< 105) in lesser OTT (< 50 days) is essential in carcinoma cervix to expect a better treatment outcome in all respects.


Intraosseous ganglia of the carpal bones.
Intraosseous ganglia are benign, cystic lesions of bone that are most commonly found in the subchondral region of long bones of the lower extremity. Reports of isolated carpal involvement are rare; however, it has been well documented that these lesions may produce chronic wrist pain. Various theories of pathogenesis have been advanced, including synovial herniation, mucoid degeneration, primary cellular metaplasia, and chronic repetitive trauma. In our study, 11 patients (seven female, four male) with 12 lesions were treated for chronic wrist pain associated with intraosseous carpal ganglia. All patients had similar complaints preoperatively and were unable to obtain relief with rest, immobilization, or nonsteroidal medication. Aside from local tenderness over the involved bone, the physical examination was unremarkable. Acute trauma was not found to be a factor in any of these patients' histories. Eleven lesions in 10 patients were grafted with bone from the distal radius. A complete resolution of symptoms was seen at a 20-month follow-up examination.


Facile synthesis of size-tunable tin arsenide nanocrystals.
SnAs nanocrystals (NCs) were synthesized for the first time using a colloidal synthetic strategy. The size of the narrow dispersity NCs is tuned in the range of 3.2-8.0 nm. The structural characterization suggests that the NCs are NaCl type cubic crystal structures and devoid of impurities.


Quantification of pilsicainide in serum by capillary electrophoresis.
A new method for determining pilsicainide concentration in serum by rapid and selective capillary electrophoresis has been developed and validated. For pretreatment, serum was made alkaline and then extracted with diethyl ether. Procainamide was used as an internal standard. Sodium dihydrogenphosphate buffer (pH 2.29; 0.1 M) was used as a running buffer. A fused-silica capillary tube was loaded with a voltage of 25 kV and detection was performed at UV 200 nm. Good linearity (0-2.5 microg/ml) was obtained with the minimum limit of detection being 0.04 microg/ml serum (signal-to-noise ratio, 3:1). The R.S.D. of within-run reproducibility was 0.798-2.32%, that of between-run reproducibility was 4.74-5.12% and the recovery rate was 61-63%. Disopyramide, another anti-arrhythmic drug, was close to pilsicainide in terms of migration time. This method was applied to determination of pilsicainide in serum samples.


Rapid homogeneous detection of biological assays using magnetic modulation biosensing system.
A magnetic modulation biosensing system (MMB) [1,2] rapidly and homogeneously detected biological targets at low concentrations without any washing or separation step. When the IL-8 target was present, a 'sandwich'-based assay attached magnetic beads with IL-8 capture antibody to streptavidin coupled fluorescent protein via the IL-8 target and a biotinylated IL-8 antibody. The magnetic beads are maneuvered into oscillatory motion by applying an alternating magnetic field gradient through two electromagnetic poles. The fluorescent proteins, which are attached to the magnetic beads are condensed into the detection area and their movement in and out of an orthogonal laser beam produces a periodic fluorescent signal that is demodulated using synchronous detection. The magnetic modulation biosensing system was previously used to detect the coding sequences of the non-structural Ibaraki virus protein 3 (NS3) complementary DNA (cDNA) [2]. The techniques that are demonstrated in this work for external manipulation and condensation of particles may be used for other applications, e.g. delivery of magnetically-coupled drugs in-vivo or enhancing the contrast for in-vivo imaging applications.


Colonization of Polystyrene Microparticles by Vibrio crassostreae: Light and Electron Microscopic Investigation.
Microplastics collected at sea harbor a high diversity of microorganisms, including some Vibrio genus members, raising questions about the role of microplastics as a novel ecological niche for potentially pathogenic microorganisms. In the present study, we investigated the adhesion dynamics of Vibrio crassostreae on polystyrene microparticles (micro-PS) using electronic and fluorescence microscopy techniques. Micro-PS were incubated with bacteria in different media (Zobell culture medium and artificial seawater) with or without natural marine aggregates. The highest percentage of colonized particles (38-100%) was observed in Zobell culture medium, which may be related to nutrient availability for production of pili and exopolysaccharide adhesion structures. A longer bacterial attachment (6 days) was observed on irregular micro-PS compared to smooth particles (<10 h), but complete decolonization of all particles eventually occurred. The presence of natural marine agreggates around micro-PS led to substantial and perennial colonization featuring monospecific biofilms at the surface of the aggregates. These exploratory results suggest that V. crassostreae may be a secondary colonizer of micro-PS, requiring a multispecies community to form a durable adhesion phenotype. Temporal assessment of microbial colonization on microplastics at sea using imaging and omics approaches are further indicated to better understand the microplastics colonization dynamics and species assemblages.


Effects of luminance contrast, averaged luminance and spatial frequency on vection.
Changing the speed, size and material properties of optic flow can significantly alter the experience of vection (i.e. visually induced illusions of self-motion). Until now, there has not been a systematic investigation of the effects of luminance contrast, averaged luminance and stimulus spatial frequency on vection. This study examined the vection induced by horizontally oriented gratings that continuously drifted downwards at either 20° or 60°/s. Each of the visual motion stimuli tested had one of: (a) six different levels of luminance contrast; (b) four different levels of averaged luminance; and (c) four different spatial frequencies. Our experiments showed that vection could be significantly altered by manipulating each of these visual properties. Vection strength increased with the grating's luminance contrast (in Experiment 1), its averaged luminance (in Experiment 2), and its spatial frequency (in Experiment 3). Importantly, interactions between these three factors were also found for the vection induced in Experiment 4. While simulations showed that these vection results could have been caused by effects on stimulus motion energy, differences in perceived grating visibility, brightness or speed may have also contributed to our findings.


Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease.
Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Altered homeostasis of CD4(+) FoxP3(+) regulatory T-cell subpopulations in systemic lupus erythematosus.
The role of naturally occurring regulatory T cells (Treg), known to be phenotypically heterogeneous, in controlling the expression of systemic lupus erythematosus (SLE) is incompletely defined. Therefore, different subpopulations of CD4(+) FoxP3(+) Tregs in patients with active or inactive SLE were investigated and compared with those of healthy subjects and patients with ankylosing spondylitis (AS). Characterization of different subsets of circulating CD4(+) FoxP3(+) Tregs was examined using flow cytometry. CD4(+) CD25(high) T cells were sorted and examined for suppressive activity in vitro. The results showed first that a significant decrease in the frequency of CD4(+) CD25(high) FoxP3(+) T cells was present in patients with active SLE (n = 58), compared with healthy controls (n = 36) and AS patients (n = 23). In contrast, the frequencies of CD25(low) FoxP3(+) and CD25(-) FoxP3(+) CD4(+) T cells were significantly increased in patients with active SLE by comparison with the control subjects. The elevation of these two putative Treg subpopulations was associated with lower plasma levels of complement C3 and C4 in patients with SLE. In addition, the ratios of the three subsets of CD4(+) FoxP3(+) Tregs versus effector T cells (CD4(+) CD25(+) FoxP3(-)) were inversely correlated with the titer of anti-double-stranded DNA IgG in patients with inactive, but not active, SLE. These results suggest that the pathogenesis of SLE may be associated with a defect in the homeostatic control of different Treg subsets.


The influence of concomitant HIV infection on the serological diagnosis of primary syphilis in southern Africa.
The authors investigated the utility of both a nontreponemal (RPR) test and a treponemal (FTA-ABS) test for the diagnosis of primary syphilis during the emergence of the HIV epidemic in southern Africa. The serological tests were performed on 868 patients with genital ulcerations, seen in five centres. While primary syphilis was diagnosed by multiplex PCR in 163 cases (18.8%), the overall RPR and FTA-ABS seroprevalences were 24.3% and 51.5% respectively. The sensitivities of the RPR and FTA-ABS to detect primary syphilis were 69.3% and 89.6% respectively, while the specificities were 86.1% and 58.5% respectively. The performance characteristics of these tests were influenced negatively by concomitant HIV infection and the presence of other genital ulcer disease pathogens in lesions found to be Treponema pallidum PCR positive.


The immunodeficiency virus coreceptor, Bonzo/STRL33/TYMSTR, is expressed by macaque and human skin- and blood-derived dendritic cells.
Dendritic cells (DCs) have been shown to be important in the replication of human and simian immunodeficiency viruses (HIV and SIV, respectively) in vivo and in vitro. DCs express CD4 and several chemokine receptors, such as CCR5 and CXCR4, which are important for viral entry. In vivo, DCs are abundant at body surfaces, where they might be one of the first cells that encounter naturally transmitted virus. Furthermore, DCs pulsed with HIV or SIV in vitro can efficiently transmit virus to T cells, thereby propagating vigorous viral replication. Reports have implicated Bonzo/STRL33/TYMSTR to be an additional alternative coreceptor for HIV and especially SIV infection. However, at present there are no reports regarding the expression of Bonzo/STRL33/TYMSTR by human or macaque DCs. Here we demonstrate the presence of Bonzo/STRL33/TYMSTR transcripts in rhesus macaque and human skin-derived DCs, in immature and mature blood monocyte-derived DCs, and in T cells from both skin and blood. Therefore, Bonzo/STRL33/TYMSTR is expressed in DCs and T cells that can play a role in the transmission of immunodeficiency viruses.


Review on Epileptic Seizure Prediction: Machine Learning and Deep Learning Approaches.
Epileptic seizures occur due to brain abnormalities that can indirectly affect patient's health. It occurs abruptly without any symptoms and thus increases the mortality rate of humans. Almost 1% of world's population suffers from epileptic seizures. Prediction of seizures before the beginning of onset is beneficial for preventing seizures by medication. Nowadays, modern computational tools, machine learning, and deep learning methods have been used to predict seizures using EEG. However, EEG signals may get corrupted with background noise, and artifacts such as eye blinks and physical movements of muscles may lead to "pops" in the signal, resulting in electrical interference, which is cumbersome to detect through visual inspection for longer duration recordings. These limitations in automatic detection of interictal spikes and epileptic seizures are preferred, which is an essential tool for examining and scrutinizing the EEG recording more precisely. These restrictions bring our attention to present a review of automated schemes that will help neurologists categorize epileptic and nonepileptic signals. While preparing this review paper, it is observed that feature selection and classification are the main challenges in epilepsy prediction algorithms. This paper presents various techniques depending on various features and classifiers over the last few years. The methods presented will give a detailed understanding and ideas about seizure prediction and future research directions.


Center of cancer systems biology second annual workshop--tumor metronomics: timing and dose level dynamics.
Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized.


[Laparoscopy in diagnosis and treatment of acute abdominal diseases in children].
2765 children with abdominal pains were observed in the clinic of pediatric surgery from 1995 to 1999. During the observation period the abdominal pains persisted in 85 children. As it was not possible to resect the acute abdominal diseases, these children underwent diagnostic laparoscopy. Destructive changes in the appendix were revealed in 12 patients, 73 patients have avoided unnecessary laparotomy and appendectomy. It is concluded that diagnostic potential of laparoscopy is not inferior to diagnostic laparotomy. Moreover laparoscopy has advantage as a method of final diagnosis.


Reducing therapist contact in cognitive behaviour therapy for panic disorder and agoraphobia in primary care: global measures of outcome in a randomised controlled trial.
Panic disorder, with and without agoraphobia, is a prevalent condition presenting in general practice. Psychological treatments are effective but are limited by restricted availability. Interest has grown in methods by which the efficiency and thus availability of psychological treatments can be improved, with particular emphasis on reduced therapist contact formats. To evaluate the relative efficacy in a primary care setting of a cognitive behaviour therapy (CBT) delivered at three levels of therapist contact: standard contact, minimum contact, and bibliotherapy. A total of 104 patients were randomly allocated to receive standard therapist contact, minimum therapist contact or bibliotherapy, with 91 patients completing treatment. All patients received an identical treatment manual and were seen by the same psychologist therapist. Outcome was reported in terms of brief global ratings of severity of illness, change in symptoms, and levels of social disruption. These brief measures were chosen to be suitable for use in general practice and were used at treatment entry and endpoint. The standard therapist contact group had the strongest and most comprehensive treatment response, showing significant differences from the bibliotherapy group on all, and the minimum therapist contact group on some, endpoint measures. Some reduction in efficacy was therefore found for the reduced therapist contact groups. The standard therapist contact group showed the greatest treatment efficacy in the present study. As it was of notably shorter duration than many other current formulations of CBT, it represents a useful and efficient treatment for panic disorder and agoraphobia in primary care.


Finding community structure in very large networks.
The discovery and analysis of community structure in networks is a topic of considerable recent interest within the physics community, but most methods proposed so far are unsuitable for very large networks because of their computational cost. Here we present a hierarchical agglomeration algorithm for detecting community structure which is faster than many competing algorithms: its running time on a network with n vertices and m edges is O (md log n) where d is the depth of the dendrogram describing the community structure. Many real-world networks are sparse and hierarchical, with m approximately n and d approximately log n, in which case our algorithm runs in essentially linear time, O (n log(2) n). As an example of the application of this algorithm we use it to analyze a network of items for sale on the web site of a large on-line retailer, items in the network being linked if they are frequently purchased by the same buyer. The network has more than 400 000 vertices and 2 x 10(6) edges. We show that our algorithm can extract meaningful communities from this network, revealing large-scale patterns present in the purchasing habits of customers.


Profiling sedentary behavior in breast cancer survivors: Links with depression symptoms during the early survivorship period.
Depression symptoms are prevalent among breast cancer survivors (BCS). Reducing sedentary behavior (SED) may be a non-pharmaceutical strategy for alleviating depression symptoms. However, little is known about SED among BCS. The present study aimed to: (i) describe SED behaviors among BCS and identify unique SED groups based on different SED dimensions; (ii) identify personal and cancer-specific factors that discriminate SED clusters; and (iii) examine the association between SED clusters and depression symptoms. Baseline self-report demographic and medical information was collected from 187 BCS. SED and physical activity were assessed over seven days using an accelerometer. Self-reported depression symptoms were reported three months later. Multiple dimensions of SED were identified and examined in cluster analysis. The clusters were examined for differences using multivariate analysis of variance and chi-square analyses. The difference in depression symptoms among SED groups was assessed using an analysis of covariance. High and low SED groups were identified. Survivors in the high SED cluster were significantly older, heavier, less physically active, reported less education, and were more likely to have undergone lymph/axial node dissection. Women in the high SED cluster reported significantly higher depression symptoms prospectively (M = 9.50, SD = 6.07) compared to women in the low SED group (M = 6.89, SD = 5.18), F(8,179) = 4.97, p = 0.03, R2 = 0.34. The importance of understanding multiple dimensions of SED among BCS was highlighted. Reducing SED during the early survivorship period may alleviate depression symptoms.


Sex differences in the metabolic syndrome: implications for cardiovascular health in women.
The metabolic syndrome is a clinical condition characterized by the presence of multiple interrelated risk factors for type 2 diabetes and cardiovascular disease. Component features include dysglycemia, increased blood pressure, increased triglycerides, decreased HDL cholesterol concentrations, and obesity (in particular, abdominal obesity). The underlying biology, optimal diagnostic criteria, and clinical implications, once diagnosed, have been matter for intense debate. Despite these areas of controversy, there is now general consensus that the observed risk factor clustering signifies heightened cardiovascular risk. The influence of sex on the clinical expression and pathophysiology of the syndrome is underrecognized, and is an issue of increasing importance given the alarming increase in prevalence among young women. This minireview will highlight sex differences in the epidemiology, etiology, biology, and clinical expression of the metabolic syndrome. In particular, key sex differences include distinctions in (a) prevalence of dysglycemia, (b) body fat distribution, (c) adipocyte size and function, (d) hormonal regulation of body weight and adiposity, and (e) the influence of estrogen decline on risk factor clustering. Accumulated and emerging data convincingly demonstrate that significant heterogeneity exists between men and women developing the metabolic syndrome, in large part related to hormonal regulation of body fat distribution and attendant metabolic abnormalities.


The Transposable Element Environment of Human Genes Differs According to Their Duplication Status and Essentiality.
Transposable elements (TEs) are major components of eukaryotic genomes and represent approximately 45% of the human genome. TEs can be important sources of novelty in genomes and there is increasing evidence that TEs contribute to the evolution of gene regulation in mammals. Gene duplication is an evolutionary mechanism that also provides new genetic material and opportunities to acquire new functions. To investigate how duplicated genes are maintained in genomes, here, we explored the TE environment of duplicated and singleton genes. We found that singleton genes have more short-interspersed nuclear elements and DNA transposons in their vicinity than duplicated genes, whereas long-interspersed nuclear elements and long-terminal repeat retrotransposons have accumulated more near duplicated genes. We also discovered that this result is highly associated with the degree of essentiality of the genes with an unexpected accumulation of short-interspersed nuclear elements and DNA transposons around the more-essential genes. Our results underline the importance of taking into account the TE environment of genes to better understand how duplicated genes are maintained in genomes.


Endocrine effects of the tapeworm Ligula intestinalis in its teleost host, the roach ( Rutilus rutilus).
The effects of parasite infection by the cestode Ligula intestinalis on the reproductive function and endocrine system of wild roach Rutilus rutilus were evaluated. Gonad maturation, plasma vitellogenin, plasma steroid concentrations (i.e. progesterone, 11-keto-testosterone and 17-beta-estradiol) and brain aromatase activity were investigated in relation with parasitization. A low prevalence (8%) of ligulosed roach and a moderate impact of parasitization (mean parasitization index of 8.8%) were found in the studied population. Inhibition of gonad maturation generally resulted from infestation but 5% of the ligulosed roach nevertheless reached maturity. Main sex steroid plasma content was depleted in both genders. Male 11-keto-testosterone, female 17-beta-estradiol and progesterone plasma concentrations of both genders were, respectively, 27, 5 and 3 times lower in ligulosed fish when compared to their non-infected counterparts. Progesterone levels were negatively correlated with the parasitization index in females. Brain aromatase activity of infected roach was reduced to 50% of that of the non-infected fish. These results demonstrate significant negative effects on the reproductive function of wild roach infected by the tapeworm L. intestinalis collected from a site with low contamination.


Regulation of p27Kip1 accumulation in murine B-lymphoma cells: role of c-Myc and calcium.
IgM cross-linking induces G1 arrest and apoptosis in murine B-lymphoma cells. It prevents pRb phosphorylation by decreasing cyclin-dependent kinase 2 activity via the up-regulation of cyclin kinase inhibitor p27Kip1. Anti-IgM also causes an increase in cytosolic free calcium and a loss of c-myc mRNA and protein. This down-regulation of c-Myc is prevented by CD40L, which rescues cells from anti-IgM-induced apoptosis. In this study, we addressed the mechanism(s) of anti-IgM-induced p27Kip1 accumulation. We examined effects of early events in B-cell receptor-mediated signaling, c-Myc down-regulation, and an increase in free calcium on p27Kip1. Down-regulation of c-myc alone had no effect on p27Kip1; neither did an increase in free calcium alone. Together, these two events led to p27Kip1 induction, growth arrest, and apoptosis. CD40L, the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, and cyclosporin A all prevented anti-IgM-induced p27Kip1 accumulation, suggesting that both the decrease in c-Myc expression and an increase in free calcium are necessary for p27Kip1 up-regulation.


Screening for dementia in general hospital inpatients: a systematic review and meta-analysis of available instruments.
Dementia is common and often undiagnosed. Improving rates of diagnosis has become a key part of current dementia guidelines. Older people admitted to hospital are a potential target population for screening for dementia. The objective was to report whether instruments advocated in screening for dementia had been validated in hospital inpatients and to make recommendations on evidence-based screening for dementia in this population. a systematic review was performed by an initial electronic database search using three key search criteria. Studies were then selected in a systematic fashion using specific predetermined criteria. Pooled meta-analysis was performed. Inclusion criteria were studies where the study group were inpatients in general hospitals, including a clearly defined group of older people (60 or older), they used a recognised screening instrument compared with a reference standard, and included at least 10 cases of dementia. Demographic data as well as sensitivity and specificity were recorded from the selected studies. in total nine studies describing validation of six discreet instruments satisfied all our criteria and we were able to perform meta-analysis with one instrument, the Abbreviated Mental Test Score (AMTS). With a cut-off of <7, pooled analysis of the AMTS showed a sensitivity of 81%, a specificity of 84% and an area under the curve (AUC) of 0.88. a small number of instruments have been validated for screening for dementia in general hospital. Understanding strengths and weaknesses of currently available instruments allows informed decisions about screening in this setting.


The use of Alu-PCR to distinguish between typical pulmonary carcinoids versus classic midgut carcinoids.
Although histologically 'typical' pulmonary and 'classic' midgut carcinoids are similar, the small intestine tumors are more aggressive than their pulmonary counterpart. We believe that in contrast to pulmonary carcinoids arising from Kulchitsky cells, 'classical' midgut carcinoids develop from crypt stem cells that differentiate into endocrine ('classical') or exocrine-endocrine ('non-classical' adenocarcinoid) tumors. The different progenitor cells may determine different malignant potentials between these types of carcinoids. To identify genetic differences between 'classical' midgut and typical pulmonary carcinoids using an Alu-PCR genomic profiling method, we reviewed 54 cases of carcinoid tumors that were surgically removed at Hartford Hospital from 1996 through 2001. Histologically these cases were selected into three groups: i) foregut or pulmonary carcinoids, ii) 'classic' midgut carcinoids of small intestine and iii) multiple typical pulmonary carcinoids. Genomic-profiling of DNA from these cases was performed using an Alu-PCR method. Metastases were observed in 18/20 'classical' intestinal carcinoid tumors, 3/30 pulmonary carcinoids, and 0/4 multiple pulmonary carcinoids. These results confirm that pulmonary carcinoids behave in a more benign fashion than intestinal carcinoid tumors. Using Alu-PCR to profile tumor cell genomic DNA, we showed that 68% of small intestine carcinoids and 58% of pulmonary carcinoids had allelic banding patterns suggestive of either amplification or deletion of gene sequences. Alu-PCR demonstrated loss or gain of genetic sequences that were unique for each examined group. These findings strongly suggest that pulmonary carcinoids differ from their intestinal counterparts.


Segmental femur reconstruction using an intercalary allograft with an intramedullary vascularized fibula bone flap.
The use of intercalary allografts has been an important innovation for use in limb-salvage surgery. However, the principal disadvantage of intercalary allografts is a high incidence of nonunion, fracture, and infection. With a recent trend toward higher doses of chemotherapy, an increased incidence of nonunion and healing problems can be anticipated with the use of allografts. In this article, the authors report two cases in which a vascularized fibula bone flap was used with an intercalary allograft, utilising an intramedullary approach, for immediate femur reconstruction following sarcoma resection. The rationale for this approach is to combine the mechanical strength of an allograft with the biologic activity of a vascularized bone flap. The allograft provides bone stock and early stability, while the addition of the vascularized bone flap substantially facilitates the host-allograft union.