Wound healing of 6.45-microm free electron laser skin incisions with heat-conducting templates.
We have previously shown a reduction in lateral thermal damage with acute studies of skin incisions made in vitro using heat-conducting templates. Here we examined the wound-healing response to laser incisions with heat-conducting templates and explored the use of an optically transparent template with the free electron laser (FEL) at 6.45 microm. First we evaluated the effects of a sapphire heat-conducting template on the lateral thermal damage of FEL incisions using in vitro human skin samples. Next we compared wound tensile strength and histological scoring of the healing of incisions created on the dorsal pelts of live rats with the FEL utilizing metal and sapphire heat-conducting templates and scalpel incisions. The animals were euthanized and the wounds were analyzed at postoperative days 7, 14, and 21. The depth and lateral thermal damage of FEL incisions on in vitro human skin were significantly reduced with the sapphire heat-conducting template. Nonstatistically significant differences in wound tensile strengths and histological scoring of wound healing were noted at days 7 and 14. By day 21, all of the incisions appeared similar. When the data from days 7 and 14 were combined, statistically significant differences were found for each of the templates (except the histological evaluation with the aluminum template) and the scalpel compared with laser incisions made without using a template. The use of metal or sapphire heat-conducting templates reduced the wound-healing delay of laser incisions seen at postoperative days 7 and 14.


Safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.
We evaluated the safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer (NSCLC). We retrospectively compared toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with the same outcomes in patients aged younger than 75 years. In total, 350 patients were eligible for this analysis, of whom 92 were in the elderly group and 258 in the non-elderly group. In the elderly group, adverse events were generally mild to moderate and grade 3-4 adverse events were observed in 8 (9%) patients. The objective response rate (17 vs. 21% for elderly vs. non-elderly, respectively) and median survival time (7.6 vs. 9.3 months) were also similar in the two groups. Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). In this study, treatment with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patients.


Body composition measurement in normal children: ethical and methodological limitations.
There are significant ethical. practical and theoretical issues that need to be considered when measuring body composition in normal children. For example, when evaluating the use of techniques that involve ionizing radiation, then the benefit to the volunteer subject, or society at large, needs to be balanced against the likely harm to the subject. For children, the detriment per unit dose may be two to three times larger than that for young adults. At present the decision as to the acceptable radiation dose limit for healthy children undergoing research studies remains debatable. Most techniques for measuring body composition require specific validation of their precision and accuracy when used with small subjects; adaptation of existing methods may thus be necessary in order to measure children. In addition, techniques such as densitometry and dual energy X-ray absorptiometry may be impractical for use in young children. A major theoretical issue to be considered is that most body composition techniques assume a constant density or chemical composition of the fat-free mass (FFM). However, the FFM in children does not consist of fixed proportions of water, protein and mineral; rather, the proportions of these change during growth, with water content decreasing and protein and mineral content increasing. Caution must therefore be used in the application of adult-derived body composition constants and equations to children.


The prevention access and risk taking in young people (PARTY) project protocol: a cluster randomised controlled trial of health risk screening and motivational interviewing for young people presenting to general practice.
There are growing worldwide concerns about the ability of primary health care systems to manage the major burden of illness in young people. Over two thirds of premature adult deaths result from risks that manifest in adolescence, including injury, neuropsychiatric problems and consequences of risky behaviours. One policy response is to better reorientate primary health services towards prevention and early intervention. Currently, however, there is insufficient evidence to support this recommendation for young people. This paper describes the design and implementation of a trial testing an intervention to promote psychosocial risk screening of all young people attending general practice and to respond to identified risks using motivational interviewing. clinicians' detection of risk-taking and emotional distress, young people's intention to change and reduction of risk taking. pathways to care, trust in the clinician and likelihood of returning for future visits. The design of the economic and process evaluation are not detailed in this protocol. PARTY is a cluster randomised trial recruiting 42 general practices in Victoria, Australia. Baseline measures include: youth friendly practice characteristics; practice staff's self-perceived competency in young people's care and clinicians' detection and response to risk taking behaviours and emotional distress in 14-24 year olds, attending the practice. Practices are then stratified by a social disadvantage index and billing methods and randomised. Intervention practices receive: nine hours of training and tools; feedback of their baseline data and two practice visits over six weeks. Comparison practices receive a three hour seminar in youth friendly practice only. Six weeks post-intervention, 30 consecutive young people are interviewed post-consultation from each practice and followed-up for self-reported risk taking behaviour and emotional distress three and 12 months post consultation. The PARTY trial is the first to examine the effectiveness and efficiency of a psychosocial risk screening and counselling intervention for young people attending primary care. It will provide important data on health risk profiles of young people attending general practice and on the effects of the intervention on engagement with primary care and health outcomes over 12 months. ISRCTN16059206.


LED-based UV absorption detector with low detection limits for capillary liquid chromatography.
A 260 nm deep UV LED-based absorption detector with low detection limits was developed and integrated with a small nanoflow pumping system. The detector is small in size (5.2 × 3.0 cm) and weighs only 85 g (without electronics). This detector was specifically designed and optimized for on-column detection to minimize extra-column band broadening. No optical reference was included due to the low drift in the signal. Two ball lenses, one of which was integrated with the LED, were used to increase light throughput through the capillary column. Stray light was minimized by the use of a band-pass filter and an adjustable slit. Signals down to the parts per billion level (nanomolar) were easily detected with a short-term noise level of 4.4 μAU, confirming a low limit of detection and low noise. The detection limit for adenosine-5'-monophosphate was 230 times lower than any previously reported values. Good linearities (3 orders of magnitude) were obtained using sodium anthraquinone-2-sulfonate, adenosine-5'-monophosphate, dl-tryptophan, and phenol. The LC system was demonstrated by performing isocratic separation of phenolic compounds using a monolithic capillary column (16.5 cm × 150 μm i.d.) synthesized from poly(ethylene glycol) diacrylate.


[Study on the cost of expanded programme on immunization in areas with different economic levels].
The expanded programme on immunization (EPI) is an important part of the social commonwealth projects providing health care service by the government, which benefits communities. Government has the responsibility for EPI's financing which should be covered by the national budget. It is essential that the cost of EPI service be scientifically estimated to provide propriety information for policy makers. This study, using the cost accounting theory of health economics, to calculate EPI service cost at different levels. 3 provinces, 3 prefectures, 9 counties, 18 towns and 12 villages were selected from three provinces Guizhou, Heilongjiang and Zhejiang from the western, central and eastern regions of the country. The average costs for one EPI-targeted child in Guizhou, Heilongjiang and Zhejiang, were 15.68 Yuan, 29.00 Yuan and 31.09 Yuan, and the costs for one dose were 10.99 Yuan, 18.64 Yuan and 16.51 Yuan, respectively. The costs for complete immunization program for one child were 131.88 Yuan, 242.32 Yuan and 280.67 Yuan, respectively. The main factors affecting the cost would include the average personnel cost (salary and benefit cost) by different economic levels of areas, the number of EPI items developed, and the number of total doses for one child. (1) Obvious differences were found between different areas. (2) The proportion of the cost was not reasonably set because of the shortage of input. (3) Guideline for different areas to compensate the working item cost according to the number of the items should be formulated.


New users of antipsychotic medication: A population-based cohort study of occupational outcome measures in relation to antipsychotic on-label and off-label prescribing practices.
Treatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. Register-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. The majority of new antipsychotic users received welfare payments for prolonged periods of time during the observation period, even more so for individuals treated with antipsychotic polypharmacy or other antipsychotic combination regimens. The risk of permanently leaving the labor market was also associated with antipsychotic combination regimen. Antipsychotic treatment, especially in combination with other antipsychotics or other psychotropic drugs, could serve as a marker of subjects with increased need for support to maintain the labor market affiliation. However, causality cannot be inferred from an observational study because of residual confounding that could not be adjusted for in this study.


C/EBPbeta is required for the late phases of acute phase genes induction in the liver and for tumour necrosis factor-alpha, but not Interleukin-6, regulation.
C/EBPbeta is a leucine-zipper transcription factor believed to play an important role in the control of liver functions, and in particular in the transcriptional regulation of acute phase genes in response to several inflammatory stimuli and to recombinant cytokines. Moreover, this factor has been proposed as an important activator of several cytokine genes. We recently described the generation of mice in which the C/EBPbeta gene has been inactivated by gene targeting, showing that they are viable, but present specific defects in the myeloid and lymphoid compartments. Here we demonstrate that C/EBPbeta does indeed play a role in the transcriptional induction of some, but not all, liver acute phase genes. Activation is in particular defective in C/EBPbeta-deficient mice in the later phases of induction, suggesting that the early phases may be triggered by factors other than C/EBPs. Moreover, IL-6 activation is normal and TNFalpha activation is defective in the mutant mice, indicating a differential role of C/EBPbeta in the control of these two cytokines' production.


Outcome after recannulation and a second course of extracorporeal membrane oxygenation.
Controversy surrounds the justification of a second course of extracorporeal membrane oxygenation (ECMO) for patients that deteriorate after initial decannulation. The authors' experience with a small number of patients requiring recannulation led them to investigate the results of a second ECMO course from all institutions that report to the ELSO registry. The ELSO neonatal registry for patients that underwent multiple ECMO courses was reviewed and mortality and complication rates between first and second courses were compared. Complications were classified according to the following ELSO registry defined categories: hemorrhagic, mechanical, metabolic, infectious, renal, pulmonary, neurologic, and cardiac. Of the 16,450 patients in the ELSO neonatal registry in January 2000, 205 patients (1.25%) have required multiple ECMO courses. There have been 201 patients (1.22%) who have needed 2 courses of ECMO and 4 patients (0.024%) have undergone 3 ECMO runs. A total of 557 complications occurred during the first ECMO course in these 205 patients, and 672 complications developed during the second course. This represents an increase in the complication rate by 20.6% during the second ECMO course. Although mechanical complications were the most common, there was no change in the incidence between first and second courses. However, the frequency of complications increased in all other classifications during the second course when compared with the first. The largest increases occurred with neurologic and infectious complications (134% and 79% increases, respectively). Renal and metabolic complications also were markedly elevated (35% and 24%, respectively). Seventy-six of 201 (38%) patients who required 2 courses of ECMO and 1 of 4 patients undergoing 3 runs survived. Survival was more likely for patients with meconium aspiration. Primary pulmonary hypertension and total anomalous pulmonary venous return had low survival rates. A small subset of patients may require recannulation and a second ECMO course. Although survival may be achieved in more than one third of these patients, complication rates are increased during the second course. Specifically, neurologic, infectious, renal, and metabolic complication rates are increased. Long-term consequences of recannulation are unknown. Selection criteria identifying patients that may benefit from recannulation have not been established.


Safety of HPV vaccines in the age of nonavalent vaccination.
To date three vaccines against human papilloma virus (HPV) have been licensed: a bivalent, a quadrivalent and, in 2014, a nonavalent vaccine. Despite the early implementation of national vaccination programs, in the majority of developed countries coverage rates remain unsatisfactory. Rumors about vaccine safety have been one of the principal obstacles for the acceptance of HPV vaccination by the public. It is therefore of primary importance to provide the public with clear and up-to-date information about HPV vaccination safety. To this aim, in this narrative review we will summarize safety data from pre and postlicensure studies for the three HPV vaccines available with a focus on the safety profile of the new nonavalent vaccine.


Genome-wide miRNA profiling in myelodysplastic syndrome with del(5q) treated with lenalidomide.
Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. We investigated its effect on regulation of microRNA (miRNA) expression profiles in del(5q) patients with MDS in vivo. We used miRNA expression microarrays to study changes in miRNA levels in peripheral blood CD14+ monocytes collected from patients before and during lenalidomide treatment and compared them with those from healthy donors. Before treatment, we observed strong upregulation of pro-apoptotic miR-34a and miR-34a* that diminished during lenalidomide exposure. Upregulation of HOX-related miR-196b and erythroid-specific miR-451 seen in untreated patients remained unchanged after the treatment. At the time of hematologic response, expression of several miRNAs clustering to the 14q32 locus was reduced. Additionally, we focused more deeply on miRNAs from the 5q commonly deleted region and found that levels of miR-378 and miR-378* followed haploinsufficiency trend. This report describes changes in miRNA expression in del(5q) patients with MDS treated with lenalidomide, likely arising from deregulation of pathways implicated in lenalidomide action.


Location-specific technical nuances of spinal meningioma resection: an operative video case series.
The objective of this video was to demonstrate technical nuances of intradural spinal meningioma (ISM) resection through a high-quality surgical video. The authors describe 3 patients with ISM in the cervicomedullary, cervical, and thoracic regions. Patients underwent surgery in the prone position with laminectomy, dorsal durotomy, and then resection of the mass. Case 1 required a suboccipital craniectomy and dissection of the tumor away from the vertebral artery. In case 2, special emphasis is placed on sectioning the dentate ligament with cord rotation. Case 3 highlights meticulous circumferential arachnoid release and the use of ultrasound. Patients saw significant neurological improvement postoperatively. This video provides clear instruction on location-specific technical nuances of ISM removal.


Mating patterns of black oak Quercus velutina (Fagaceae) in a Missouri oak-hickory forest.
Wind-pollinated forest trees usually have high outcrossing rates, but allogamy does not necessarily translate into high pollen movement. The goal of this study was to determine the outcrossing rates, pollen pool genetic structure, and the size of the effective pollination neighborhood in a population of black oak, Quercus velutina, in a Missouri oak-hickory forest. Based on 6 allozyme loci, 12 maternal trees, and 439 progenies sampled along a transect of 1300 m, we found complete outcrossing (t(m) = 1.000, P < 0.001) and small amounts of biparental inbreeding. Using a TwoGener analysis of the pollen gene pool, we found significant structure across maternal plants (Phi(FT) = 0.078, P < 0.001), which when corrected for adult inbreeding translates into Phi(FT) = 0.066 that corresponds to an effective number of pollen donors of 7.5 individuals. Assuming a bivariate normal distribution and an adult density of 16.25 trees ha(-1), we estimated that the effective pollination neighborhood area had a radius of 41.9 m. Even assuming that our estimates may be conservative, these findings join a growing body of evidence that suggest that the local neighborhood of wind-pollinated forest tree populations may be relatively small creating opportunities for local selection and genetic drift.


Variation in Milk Proteins Across Lactation in Pongo pygmaeus and Gorilla gorilla.
Milk is a critical nutrition source for all neonatal mammals. In addition to nutrition, milk contains a multitude of bioactive molecules that likely affect neonatal physiology, metabolism, and immune function. We suggest that changes in the milk proteome across lactation reflect the changing need of the neonate and juvenile offspring. We used mass spectrometry to characterize the milk proteomes from a Pongo pygmaeus (12 samples) and a Gorilla gorilla (6 samples) housed at the Smithsonian's National Zoo and Conservation Biology Institute and trained to give milk samples. We found a total of 454 proteins from P. pygmaeus and 428 proteins from G. gorilla. We specifically characterized changes across lactation in 13 proteins representing multiple compartments of milk, including the milk fat globule membrane and whey. Additionally, we characterized changes in various immunoglobulin types, finding similarities to previously published studies on primate milks. Despite broad similarities between the milk proteomes of these two apes, we demonstrated that proteomes from samples from 8 to 12 months clustered by species/individual and were distinct. Samples from more individuals are required to distinguish whether our result demonstrates species differences or individual differences. This study represents a baseline study that other zoo-based milk studies can build from. All RAW data, MetaMorpheus search results, and PAW_BLAST results are available on MassIVE at ftp://massive.ucsd.edu/MSV000089723/.


Multivalent effects of RGD peptides obtained by nanoparticle display.
The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.


A biokinetic model for predicting the retention of 3H in the human body after intakes of tritiated water.
Scarce published data on the long-term excretion of tritiated water from the human body have been re-evaluated in order to develop a biokinetic model describing the retention in the human body of 3H from tritiated water (HTO) that could be used for both prospective and retrospective radiation protection. A three-component exponential function is proposed to describe the elimination of 3H from HTO with biological half-times of 10 d (99.00%), 40 d (0.98%) and 350 d (0.02%) respectively. The model predicts a committed effective dose of 1.7 x 10(-11) Sv Bq(-1), comparable with that of the current ICRP Publication 56 and 72 models, and estimates the retention of 3H to within a factor of about 2 of the measured values up to 40 d after intake and about 5 at times longer than 100 d. The derivation of the model and the uncertainties associated with the various parameters are discussed.


Glycine-immunoreactive terminals in the rat trigeminal motor nucleus: light- and electron-microscopic analysis of their relationships with motoneurones and with GABA-immunoreactive terminals.
Post-embedding immunolabelling methods were applied to semi-thin and ultrathin resin sections to examine the relationships between glycine- and gamma-aminobutyric acid (GABA)-immunoreactive terminals on trigeminal motoneurones, which were identified by the retrograde transport of horseradish peroxidase injected into the jaw-closer muscles. Serial sections were cut through boutons and alternate sections were incubated with antibodies to glycine and GABA. Light-microscopic analysis of semi-thin sections revealed a similar pattern of glycine and GABA-immunoreactive boutons along the motoneurone soma and proximal dendrites, and of immunoreactive cell bodies in the parvocellular reticular and peritrigeminal areas surrounding the motor nucleus. Immunoreactive synaptic terminals on motoneurones were identified on serial ultrathin sections at electron-microscopic level using a quantitative immunogold method. Three populations of immunolabelled boutons were recognized: boutons immunoreactive for glycine alone (32%), boutons immunoreactive for GABA alone (22%), and boutons showing co-existence of glycine and GABA immunoreactivities (46%). Terminals which were immunoreactive for glycine only contained a higher proportion of flattened synaptic vesicles than those which were immunoreactive for GABA only, which contained predominantly spherical vesicles. Terminals which exhibited both immunoreactivities contained a mixture of vesicle types. All three classes of terminal formed axo-dendritic and axo-somatic contacts onto retrogradely labelled motoneurones. A relatively high proportion (25%) of boutons that were immunoreactive for both transmitters formed synapses on somatic spines. However, only GABA-immunoreactive boutons formed the presynaptic elements at axo-axonic contacts: none of these were found to contain glycine immunoreactivity. These data provide ultrastructural evidence for the role of glycine and GABA as inhibitory neurotransmitters at synapses onto jaw-closer motoneurones, but suggest that presynaptic control of transmission at excitatory (glutamatergic) synapses on motoneurones involves GABAergic, but not glycinergic inhibition.


Electron-impact ionization of CCl4 and CCl2F2.
Absolute partial and total cross sections for electron-impact ionization of CCl4 and CCl2F2 are reported for electron energies from threshold to 1000 eV. The product ions are mass analyzed using a time-of-flight mass spectrometer and detected with a position-sensitive detector whose output demonstrates that all product ion species are collected with equal efficiency irrespective of their initial kinetic energies. Data are presented for production of CCl3(+), CCl2(+), CCl+, C+, Cl2(+), and CCl3(2+) from CCl4; and for production of CCl(2)F+, CClF2(+), CClF(+), (CCl+ + CF2(+)), Cl+, CF+, F+, and C+ from CCl2F2. Data are also reported for formation of (CCl2(+),Cl+) and (CCl+, Cl+) ion pairs from CCl4. The total cross section for each target is obtained as the sum of the partial cross sections. The overall uncertainty in the absolute cross sections for most of the singly charged ions is +/- 5-7 %. The present partial cross sections for lighter fragment ions are found to be considerably greater than had been previously reported but the most recent total cross section measurements agree well with those reported here. Neither the binary-encounter-Bethe theory nor the Deutsch-Mark theory reproduces the experimental cross sections correctly for both targets.


Environmental Risk of Metal Contamination in Sediments of Tropical Reservoirs.
Reservoir sediment can work as both sink and source for contaminants. Once released into the water column, contaminants can be toxic to biota and humans. We investigate potential ecological risk to benthic organisms by metals contamination in six reservoirs in Southeast Brazil. Results of the bioavailable fraction of copper (Cu), chromium (Cr), cadmium (Cd), lead (Pb), zinc (Zn), and iron (Fe) in sediment samples are presented. Considering Cu, Cd, and Zn concentrations, about 6% of the samples exceeded the threshold effect levels of sediment quality guidelines. The comparison to sediment quality guidelines is conservative because we used a moderate metal extraction. Control of contaminant sources in these reservoirs is key because they are sources of water and food. The mixture toxicity assessment showed an increased incidence of toxicity to aquatic organisms showing that mixture toxicity should be taken into account in sediment assessment criteria.


A network meta-analysis of therapeutic and prophylactic management of vasospasm on aneurysmal subarachnoid hemorrhage outcomes.
Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all available strategies targeting vasospasm and cerebral ischemia on outcomes in a network meta-analysis. We searched EMBASE and MEDLINE databases from 1 January 1990 and 28 November 2021 according to PRISMA guidelines. Randomized controlled trials and longitudinal studies were included. All curative or preventive strategies targeting vasospasm and/or cerebral ischemia were eligible. A network meta-analysis was performed to compare all interventions with one another in a primary (randomized controlled trials only) and a secondary analysis (both trials and longitudinal studies). Mortality by 3 months was the primary outcome. Secondary outcomes were vasospasm, neurological outcome by 3 months, and dichotomized as "good" or "poor" recovery according to each study definition. A total of 2,382 studies were screened which resulted in the selection of 192 clinical trials (92 (47.9%) and 100 cohorts (52.1%) and the inclusion of 41,299 patients. In randomized controlled studies, no strategy decreased mortality by 3 months. Statins (0.79 [0.62-1]), tirilazad (0.82 [0.69-0.97]), CSF drainage (0.47 [0.29-0.77]), and clazosentan (0.51 [0.36-0.71]) significantly decreased the incidence of vasospasm. Cilostazol was the only treatment associated with improved neurological outcomes by 3 months in the primary (OR 1.16, 95% CI [1.05-1.28]) and secondary analyses (OR 2.97, 95% CI [1.39-6.32]). In the modern era of subarachnoid hemorrhage, all strategies targeting vasospasm failed to decrease mortality. Cilostazol should be confirmed as a treatment to improve neurological outcomes. The link between vasospasm and neurological outcome appears questionable. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=116073, identifier: PROSPERO CRD42018116073.


A dynamical (e,2e) investigation of the structurally related cyclic ethers tetrahydrofuran, tetrahydropyran, and 1,4-dioxane.
Triple differential cross section measurements for the electron-impact ionization of the highest occupied molecular orbitals of tetrahydropyran and 1,4-dioxane are presented. For each molecule, experimental measurements were performed using the (e,2e) technique in asymmetric coplanar kinematics with an incident electron energy of 250 eV and an ejected electron energy of 20 eV. With the scattered electrons being detected at -5°, the angular distributions of the ejected electrons in the binary and recoil regions were observed. These measurements are compared with calculations performed within the molecular 3-body distorted wave model. Here, reasonable agreement was observed between the theoretical model and the experimental measurements. These measurements are compared with results from a recent study on tetrahydrofuran [D. B. Jones, J. D. Builth-Williams, S. M. Bellm, L. Chiari, C. G. Ning, H. Chaluvadi, B. Lohmann, O. Ingolfsson, D. Madison, and M. J. Brunger, Chem. Phys. Lett. 572, 32 (2013)] in order to evaluate the influence of structure on the dynamics of the ionization process across this series of cyclic ethers.


Oral bisphosphonate-induced osteonecrosis complications in patients undergoing tooth extraction: a systematic review and literature updates.
Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications. A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA. The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications. Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.


Toll-like receptor 2-independent and MyD88-dependent gene expression in the mouse brain.
Toll-like receptors (TLRs) are essential to mount a rapid innate immune reaction to pathogens. Although TLR2 is the key receptor for pathogen-associated molecular patterns from Gram-positive bacteria, a robust transcriptional activation of the gene encoding this receptor takes place in the brain of mice exposed to the TLR4 ligand lipopolysaccharide (LPS). TLR2 gene expression is actually used as a reliable marker of activated microglia in vivo, but its functions remain unknown. The present study investigated the role of this receptor in mediating LPS-induced gene expression in the mouse brain. Immune genes were measured using both in situ hybridization and real time RT-PCR. Despite the robust microglial TLR2 expression, this receptor does not modulate transcriptional activity by TLR4 signaling. TLR2-deficient mice and their wild-type littermates had similar IkappaBalpha mRNA levels and induction of innate immune genes from 6 h to 10 days after LPS injection. In contrast, NF-kappaB activity, cytokine, chemokine, TLR2 and CD14 transcripts were no longer detected in MyD88-deficient mice. Indeed, the hybridization signal for most of the transcripts measured in this study was similar in the brain of MyD88(-/-) mice exposed to either saline or LPS. These data indicate that while TLR2 transcription is dependent on MyD88 signaling in microglia, this innate immune receptor is not involved in the immune response to LPS. On the other hand, MyD88 pathway is essential for the endotoxin to induce expression of immune genes in the central nervous system.


Effects of intraoperative PEEP on postoperative arterial oxygenation.
Previous studies have suggested that early postoperative hypozemia may be due to a reduction of functional residual capacity (FRC) during anesthesia and surgery. Positive end-expiratory pressure (PEEP) has been recommended as a means of maintaining FRC and improving arterial oxygenation. Fifteen selected patients undergoing peripheral surgical procedures were anesthetized with one of three types of ventilatory patterns: (1) spontaneous respiration; (2) controlled ventilation; and (3) controlled ventilation with 10 cm. of water PEEP. Pao2 were sampled at selected preoperative, intraoperative, and postoperative periods. Patients receiving PEEP maintained the highest mean Pao2 intraoperatively. However, the beneficial effect of intraoperative PEEP was not sustained in the recovery room, where all patients experienced the same degree of arterial hypoxemia.


Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs.
During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung-/-Pms2-/- mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases.


In vitro activity of fosfomycin against gram-negative urinary pathogens and the biological cost of fosfomycin resistance.
The aim of this study was to reassess the activity of fosfomycin against recently isolated uropathogens circulating in Italy and to evaluate the effect of fosfomycin resistance on the expression of several virulence traits using the rare mutant strains. In vitro activity of fosfomycin was evaluated using 441 Gram-negative organisms isolated from patients with uncomplicated urinary tract infections (UTIs). Fosfomycin was the most active antibiotic against Escherichia coli (99% susceptibility). The activity against Proteus mirabilis was more potent than that of co-trimoxazole and nitrofurantoin (87.5, 67 and 0% susceptibility, respectively). The other microorganisms, accounting for about 7% of all pathogens tested, showed variable susceptibilities to fosfomycin. Compared with susceptible strains, fosfomycin-resistant mutants showed a reduced rate of growth and were impaired in their ability to adhere to uroepithelial cells and to urinary catheters. They were also more resistant to UV irradiation and to phage T7 and showed diminished rates of colicin synthesis and transfer of plasmids.


Comparative trial between insulin glargine and NPH insulin in children and adolescents with type 1 diabetes mellitus.
The objective of this study was to compare the efficacy and safety of insulin glargine, a long-acting insulin analog, with NPH insulin in children and adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label, randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received insulin glargine once daily or NPH insulin either once or twice daily, based on their prior treatment regimen. Although there was no significant difference between the NPH insulin and insulin glargine treatment groups with respect to baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic hypoglycemic events was similar between groups; however, fewer patients in the insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe nocturnal hypoglycemia (13% vs 18%), although these differences were not statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious adverse events occurred in the insulin glargine group than in the NPH insulin group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides effective glycemic control and is well tolerated in children and adolescents with T1DM.


[Association of Deployment and Tobacco Dependence among Soldiers].
Smoking is a highly preventable risk factor. The present study investigates whether military operations abroad, as compared to deployment preparation, increase the risk of starting to smoke, enhance tobacco dependence and moderator variables can be identified on smoking behavior. The study was conducted at 2 mechanized infantry battalions with N=264 soldiers. The task force completed a deployment in Afghanistan, the control group performed a deployment training. Assessments of tobacco dependence, posttraumatic symptoms, depression and stress were done before (t1) and after (t3) deployment. In addition, one assessment was done at mid-point (t2) during deployment and during the pre-deployment training, respectively. The prevalence rate of smoking soldiers was 56,4%. 51,1% (n=135) of all examined soldiers smoked more than 20 cigarettes per day. The results show a significant increase of tobacco dependence in the task force from t1 to t3 (p=0,040) as compared to the control group. For both groups, there was no increase in starting to smoke during the period of investigation (χ²<1; n. s.). Moderator variables on smoking were not found, but there was a significant increase in posttraumatic stress symptoms in the deployed group (p=0,006). Perhaps the increase in tobacco dependence in the experimental group can be attributed to the specific burdens of deployment. If high smoking rates were to be found also in other branches of the armed services, effective smoking cessation programs should be offered more widely.


Academic gaming in nurse education.
This paper describes a study of the usefulness of academic gaming in nurse education. The research has been carried out over the course of 3 years and represents an attempt by a nurse tutor to carry out a study on research lines, during the course of normal working and with a minimum of interference to the normal working of a nurse education department. The study involved psychiatric nurse learners at Winterton Hospital, Sedgefield, Durham and attempted to assess the usefulness of academic gaming by evaluating one academic game which has been designed for nurse learners. This game aims to teach various aspects of the digestive system and digestive processes. The questions which required answers were, can nurse learners learn from academic games? Do they like this method of learning? How does this method compare with other learning methods? Eighty-six learners participated in a test/game/test situation and completed a questionnaire after playing the game. Results suggest that learners can increase their knowledge of the subject by playing the game but it may be most useful as a consolidation method. Learners most often stated that they enjoyed the game and when ranked according to preference, gaming was preferred to film, reading and discussion methods but equally preferred to the lecture method.


Significant Enhanced SO2 Resistance of Pt/SiO2 Catalysts by Building the Ultrathin Metal Oxide Shell for Benzene Catalytic Combustion.
A noble metal catalyst shows excellent low-temperature oxidation activity in the catalytic combustion of benzene but has the problem of SO2 poisoning. We all know that SO2 easily competes with the reactant molecules for adsorption of the active site and has electronic effects on the active site to deactivate the catalyst. Therefore, the sulfur resistance of catalysts is the key problem to be solved in the process of catalytic combustion of benzene. Herein, the Pt/SiO2 catalyst with an ordered mesoporous structure was prepared by a one-step hydrothermal method, and MgO, ZnO, and MnOx were, respectively, coated on the surface of Pt/SiO2 as ultrathin shells to improve the sulfur resistance of Pt/SiO2. We observed that the sulfur resistance of the Pt/SiO2 catalyst was significantly improved due to the protective effect of the metal oxide shell. By comparing the three core-shell catalysts, it was found that the Pt/SiO2@MnOx catalyst coated with a MnOx shell had the best performance. The reason was that the MnOx shell not only protected the Pt active site but also had a good electron transfer effect on the core Pt, so it could effectively avoid the rapid adsorption poisoning of SO2 on the active Pt0 site. In addition, it was verified that the excellent redispersion of MnOx species in a SO2 atmosphere could increase the low-temperature oxidation activity of the Pt/SiO2@MnOx catalyst. Meanwhile, in situ DRIFT results also confirmed that the MnOx shell could significantly promote the oxidation of benzene molecules in the SO2 atmosphere.


Encoding and display with stereo split-ring resonator arrays.
In this Letter, we report on encoding and display based on stereo standing U-shaped resonator (SUSR) arrays. The SUSR serves as a perfect absorber at a structure-dependent frequency when the polarization of incident light is parallel to the bottom rim of the SUSR. When the incidence polarization is rotated for 90° (perpendicular to the bottom rim of the SUSR), the SUSR turns to a perfect reflector at broadband frequencies. Further, the resonant frequency sensitively depends on the height of the arms of the SUSR. By introducing SUSRs with different arm heights, a resonant absorption state may occur at different frequencies. By defining the resonant absorption state as "dark" and the reflection state as "bright," we can encode and display binary patterns. Beside, when the SUSR rotates with the direction of the standing arms as axis, a different reflectivity, hence, a different shade will be generated. In this way, we may realize a grayscale display. Experimentally, we demonstrate that this encoding and display scheme indeed works.


Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase.
Recently, 2-halogenated deoxyadenosine analogs (F, Cl, and Br) have been shown to have antitumor activity. These analogs are phosphorylated by cells and are believed to exert their cytotoxic action at the nucleoside triphosphate level. In this work the interaction of these nucleoside triphosphate analogs with potential targets, such as DNA polymerase alpha, beta, and gamma, DNA primase, and ribonucleotide reductase was examined in detail. All of these compounds competitively inhibited the incorporation of dAMP into DNA by DNA polymerase alpha, beta, or gamma. F-dATP was able to completely substitute for dATP using DNA polymerase alpha and gamma, but not with DNA polymerase beta. Cl-dATP and Br-dATP substituted poorly for dATP using DNA polymerase alpha and beta. Extension of a 32P-labeled primer by DNA polymerase alpha, beta, or gamma on a single-stranded M13 template showed that these compounds were incorporated into the 3' end of the growing DNA chain and that elongation beyond the incorporated analogs was significantly retarded for Cl-dATP and Br-dATP using either DNA polymerase alpha or beta. DNA primase using poly(dC) as template was inhibited by these compounds at a concentration 4 to 5 times greater than that required for 2-F-araATP. The 2-halogenated dATP analogs were potent inhibitors of ADP reduction by ribonucleotide reductase. In conclusion, the cytotoxic action of 2-Cl-deoxyadenosine and 2-Br-deoxyadenosine may partially be mediated through the mechanism of "self-potentiation," by depression of the deoxynucleoside triphosphate pools due to inhibition of ribonucleotide reductase, which would facilitate their incorporation into DNA and result in the inhibition of DNA synthesis.


Migratory Fish Bone in the Thyroid Gland: Case Report and Literature Review.
Foreign body stuck in the throat is a common emergency case, which can be removed by the endoscopic treatment. Fish bones are one of the common observed foreign bodies in the pharynx or cervical esophagus. Fish bones have a risk of damaging the mucosa when lodged in the upper digestive tract. Foreign bodies of fish bones located outside the laryngopharyngeal tissue are relatively unusual, and it is even more rare that they remain in the thyroid. It may cause local infection, abscess formation, large blood vessels rupture, and other serious life-threatening complications when the position of the fish bone migrates to the neck. We present a unique case of a 31-year-old woman in whom a fish bone was found in the thyroid. The fish bone had been removed successfully two months after the onset of symptoms. The relevant literature is reviewed and summarized. A foreign body which is located in the neck area by swallowing is usually found in the emergency case. One of the commonest foreign bodies is the fish bone. The common presenting symptoms include foreign body (FB) sensation and or a sharp pain during swallowing. But we report a rare case in which a migratory fish bone stuck in the thyroid gland was found after 3 months. We retrieved previous literature and made a summary. Fish bones are not easy to be found as a foreign body. Surgeons should be aware that fish bones can become lodged in the thyroid gland. Combined with the history should be a wary fish bone to migrate to the case of the thyroid, to avoid misdiagnosis. To confirm the diagnosis, we can take ultrasound, computerized tomographic scanning (CT), and other tests.


Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia.
IL-12 has long been considered important in the pathogenesis of multiple sclerosis. However, evidence from recent studies strongly supports the critical role of IL-12-related proinflammatory cytokine IL-23, but not IL-12, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of this disease. The role of IL-23 in the CNS immunity of multiple sclerosis patients has not been elucidated; nor is it known whether human microglia produce this cytokine. In this study we investigated the expression of IL-23p19 and p40, with its key subunit p19 as the focus, in histologically characterized CNS specimens from multiple sclerosis and control cases using in situ hybridization and immunohistochemistry. A significant increase in mRNA expression and protein production of both subunits of IL-23 was found in lesion tissues compared with non-lesion tissues. Double staining showed that activated macrophages/microglia were an important source of IL-23p19 in active and chronic active multiple sclerosis lesions. We also detected IL-23p19 expression in mature dendritic cells which were preferentially located in the perivascular cuff of active lesions. The finding that human microglia produce IL-23 was further confirmed by the inducible production of IL-23p19 and p40 in cultured human microglia in vitro upon different Toll-like receptor stimulations. Taken together, these findings on the expression of IL-23p19 in multiple sclerosis lesions may lead to a better understanding of the events culminating in human multiple sclerosis.


Mothers' Involvement in Pediatric Postoperative Pain Care in a Tertiary Healthcare Setting in Saudi Arabia.
Background Many children feel moderate to intense pain in the hospital following surgery. Untreated pain can have deleterious physical and psychological effects. Mothers' involvement in child pain care and management postoperatively has been shown to be important in improving the outcomes and experiences of children, mothers, and health professionals. Aims To explore mothers' involvement in postoperative pain care and management of their children during hospitalization and following discharge and identify approaches to improve management and participation activities. Methods We used a qualitative single case study design with thematic analysis. The analysis included 20 mother-child dyads and 21 nurses, involving observation of participants and semi-structured interviews of mothers and nurses. The analysis also incorporated a review of documents from the pediatric surgical department (hospital policies and forms). Findings The following main themes and sub-themes were generated from the data: (i) provision of pain information (expected type, frequency, and duration of pain after surgery, pain intensity score, pain relief medication, and pain management methods), (ii) communication deficiency (language barrier and breakdown in communication between health professionals), (iii) emotional and physical support (family support, environmental comfort, and sleep and meal requirements), (iv) social and cultural influences (patriarchal society, cultural and religious beliefs, and work status), and (v) hospital facilities, provisions, and services (entertainment, follow-up programs, education courses on pain management for nurses, and materials and services). Conclusions The study examined mothers' participation in postoperative pain care and management in a cohort of children admitted to a tertiary care setting in Saudi Arabia, highlighting key factors that influence involvement and suggesting approaches for improving participation.


Madras pattern of motor neuron disease: improvement of symptoms with intravenous immunoglobulin.
A 13-year-old Chinese boy with features of the Madras pattern of motor neuron disease (MMND) presented to us. The benign focal atrophy of the extremities, especially the upper, and associated hearing impairment were important clues to the clinical diagnosis. A recent pathological report suggests that an inflammatory aetiology needs to be considered for this special type of motor neuron disease. Therefore, treatment with intravenous immunoglobulin 400 mg/kg once daily was administered for 5 days, and improvement of symptoms was noted at 6 months of follow up.


Water supplementation in exclusively breastfed infants during summer in the tropics.
This study was designed to determine the need for water supplementation to maintain water homoeostasis in exclusively breastfed infants during summer in a tropical country. A prestudy questionnaire revealed that 97% of 34 nurses and 63% of 70 doctors advocated such supplementation. 45 healthy, male, exclusively breastfed babies, aged 1-4 months, were recruited from a well-baby clinic. 9 who had never received supplemental water plus a random selection of 14 others were allocated to group I (breastmilk only); the remaining 22 infants were allocated to group II (breastmilk plus supplemental fluid according to the mother's usual practice). The babies were studied at the hospital for 8 h; breastmilk intake was measured by weighing the infant before and after each feed, water intake by calibrated bottles, and urine output by accurate collection and measurement. The maximum room temperatures were 34-41 degrees C and relative humidities 9-60% (below 50% in all but 3 infants). In group II the mean water intake was 11% (95% confidence interval 7-16%) of the total fluid intake. Both breastmilk intake (274 vs 210 ml) and total fluid intake (274 vs 233 ml) were higher in group I than in group II (p = 0.003, p = 0.073, respectively), after adjustment for age, weight, length, room temperature, and humidity. However, there were no significant differences between the groups in urine output, urine or serum osmolality, weight change, or rectal temperature whether or not the factors adjusted for included total fluid intake. Thus, exclusively breastfed infants do not need supplemental water to maintain water homoeostasis; a reduced breastmilk intake is a potential disadvantage of this practice.


The air-powder dental abrasive unit--an evaluation using a model system.
Air-powder abrasive systems are used in dentistry to remove dental plaque, calculus and stain from the surfaces of teeth. A model system consisting of a thin layer (14 micron) of vacuum-deposited aluminium was used to demonstrate the effectiveness of such a system. Photomicrographic analysis showed two distinct areas of removal: an inner area where removal of aluminium was complete, surrounded by an area where removal was incomplete. With the aid of a relocation pin attached to the nozzle of the instrument it was demonstrated that nozzle-target distance, the air pressure input, the flow of water and the time of operation were all factors which affected the clinical efficiency of the instrument.


Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The Gambia.
Rotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq® (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. We compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015-2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fisher's exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). Rotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age <1 year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. Rotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.


[Penetration of cefbuperazone, a new cephamycin antibiotic, into human peritoneal exudate].
Pharmacokinetic studies were carried out on cefbuperazone ( CBPZ ) in 9 patients undergoing postoperative drainage. The concentration of CBPZ in serum and peritoneal exudate after one shot intravenous administration of 1 g was measured by bioassay and calculated respectively by two- and one-compartment open model. The results obtained were as follows: The pharmacokinetic parameters calculated from the serum levels were compared to those reported previously; T1/2 = 101 min., Vd = 4.06 L and Cl = 76 ml/min. The simulation curve of the peritoneal exudate level fit fairly with the mean values of 6 patients. It appeared that CBPZ penetrated somewhat slowly into peritoneal exudate with the peak value of 27.05 micrograms/ml at about 1 hour after the administration. The exudate levels thereafter declined more slowly than the serum ones (T1/2 = 134 min.). IT was 6.2 micrograms/ml even at 6 hours after the administration.


Design optimization and implementation of a Fourier transform spectrometer with rotating motion for 0.1 cm-1 resolution spectroscopy.
In this paper, we present the design optimization and implementation of a high-resolution near-infrared Fourier transform spectrometer (FTS) based on a rotating motion. The FTS system incorporates a rotating mirror-pair for scanning the optical path length (OPL). The design optimization process is performed to maximize the scanning range to obtain a resolution of 0.1 cm-1 while taking into account constraints on the volume of the system and the availability of commercial optics. By using a pattern search algorithm, we optimized the geometrical parameters of the rotating part, and found the best solution to satisfy the constraints. A data processing method is implemented to correct the nonlinear OPL scanning using a He-Ne laser. The performance of the implemented FTS is verified through spectral analysis within the spectral range of 1550 ± 25 nm. This spectral band corresponds to the wavelength range of the amplified spontaneous emission (ASE) obtained from an Er-doped fiber amplifier used in this study. Additionally, gas spectroscopy conducted using the FTS system successfully detects and analyzes the distinct absorption lines of hydrogen cyanide in 16.5 cm gas cell. The detection sensitivity of a single measurement is evaluated based on the noise equivalent absorption coefficient of 1.45 × 10-5 cm-1 Hz-1/2 calculated from 5-sec measurement time, 2000 spectral elements, and 208 signal-to-noise ratio with 0.2 scan/sec.


Rate of positive autoimmune markers in Human T lymphotropic virus type 1 carriers: a case-control study from Iran.
Human T lymphotropic virus type 1 (HTLV-1) infection with high prevalence in the north-east of Iran, particularly in Mashhad, can lead to adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of autoimmune diseases. The aim of the study was to examine the presence of autoimmune markers in HTLV carries. Serum samples were obtained from blood donors in Mashhad, northeastern Iran. One hundred and five HTLV-1 positive (cases) and 104 age- and sex-matched HTLV-1 negative donors (controls) were assessed for presence of serum autoimmune markers by enzyme-linked immunosorbent assay. The mean ages of cases and controls were 40.8 ± 9.4 and 41.5 ± 9.3 years, respectively (P = 0.5). In the case group, 81.9% and in the control group 83.7% were male (P = 0.74). The frequency of positive antinuclear antibodies and anticyclic citrullinated peptide antibodies in the serum of the two groups were not significantly different (P = 0.68 and P = 0.62, respectively). Only one antineutrophil cytoplasmic antibody-positive case (1%) was observed in the group and no anti-phospholipid immunoglobulin G positivity was observed. The frequency of rheumatoid factor (RF) was greater in case group than in the control group, although the difference was not significant (P = 0.08). The amount of RF in all 12 RF positive sera were higher than normal levels (33-37 IU/mL). Because we failed to detect any significant relation between serum autoimmune markers and HTLV-1 infection, and because of the relatively low prevalence of autoimmune diseases, it could be concluded that healthy HTLV-1 carriers do not produce rheumatologic-related auto-antibodies more than the healthy population.


Prognostic value of negative stress cardiac magnetic resonance imaging in patients with moderate-severe coronary artery stenosis.
This study aims to evaluate the prognostic value of stress cardiac magnetic resonance (CMR) without inducible ischemia in a real-world cohort of patients with known severe coronary artery stenosis. The prognosis of patients with severe coronary artery stenosis and without inducible ischemia using stress CMR remains uncertain, even though its identification of functionally significant coronary artery disease (CAD) is excellent. Patients without inducible ischemia and known CAD who underwent stress CMR between February 2015 and December 2016 were included in this retrospective study. These patients were divided into two groups: group 1 with stenosis of 50%-75% and group 2 with stenosis of >75%. The primary endpoint was defined as the occurrence of a major adverse cardiovascular event (MACE) [cardiac death, non-fatal myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Real-world data collected from 169 patients with a median age of 69 (60-75) years were included. The median follow-up was 5.5 (IQR 4.1-6.6) years. Events occurred after a mean time of 3.0 ± 2.2 years in group 1 and 3.7 ± 2.0 years in group 2 (p = 0.35). Sixteen (18.8%) patients in group 1 and 23 (27.4%) patients in group 2 suffered from MACE without a significant difference between the two groups (p = 0.33). In group 2, one cardiac death (1.2%), seven non-fatal MI (8.3%), 15 PCI (17.9%), and one CABG (1.2%) occurred. The findings of this pilot study suggest that long-term outcomes in a real-world patient cohort with known severe and moderate coronary artery stenosis but without inducible ischemia were similar. Stress CMR may provide valuable risk stratification in patients with angiographically significant but hemodynamically non-obstructive coronary lesions.


Development and application of transseptal left heart catheterization.
The recent interest in transseptal left heart catheterization affords an opportunity to review the development and application of this procedure. This review briefly follows the history of right and left heart catheterization to the development of the transseptal procedure. A detailed description of the technique of transseptal catheterization is provided, as well as the indications and contraindications to its use. A learning curve is associated with this technique and is inversely related to the complication rate of the transseptal approach. Physicians working in high volume catheterization laboratories may gain the experience to safely perform transseptal left heart catheterization on carefully selected patients.


Topiramate induced metabolic acidosis and kidney stones - a case study.
The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones. The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed. The results revealed negative base excess in extracellular fluid of - 9.2 mmol/L, low serum HCO3- concentration (18.6 mmol/L), trend to alkaline urine (pH 6.39) and low urine citrate concentration (0.3 mmol/24h). After topiramate withdrawal, all parameters of the internal environment normalized. This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.


Lanthanocene and Cerocene Alkyl Complexes: Synthesis, Structure, and Reactivity Studies.
Lanthanocene and cerocene alkyl complexes [η5-1,3-(Me3C)2C5H3]2Ln(CH2C6H4-o-NMe2) (Ln = La 3 and Ce 4) were obtained from the salt metathesis of {[η5-1,3-(Me3C)2C5H3]2Ln(μ3-κ3-O3SCF3)2K(THF)2}2·THF (Ln = La 1·THF and Ce 2·THF) with LiCH2C6H4-o-NMe2. Reactivity of 3 and 4 toward various small molecules provides access to a series of lanthanide derivatives. For example, reactions of 3 and 4 with elemental chalcogens (sulfur and selenium) in 1:1 molar ratio give the lanthanide thiolates {[η5-1,3-(Me3C)2C5H3]2Ln(μ-SCH2C6H4-o-NMe2)}2 (Ln = La 5 and Ce 6) and selenolates {[η5-1,3-(Me3C)2C5H3]2Ln(μ-SeCH2C6H4-o-NMe2)}2 (Ln = La 7 and Ce 8). The compounds 3 and 4 react with two equivalents of elemental chalcogens (sulfur and selenium) to afford the lanthanide disulfides {[η5-1,3-(Me3C)2C5H3]2Ln}2(μ-η2:η2-S2) (Ln = La 9 and Ce 10) and diselenides {[η5-1,3-(Me3C)2C5H3]2Ln}2(μ-η2:η2-Se2) (Ln = La 11 and Ce 12). The lanthanide disulfides (9 and 10) or diselenides (11 and 12) can also be readily obtained through oxidation of the corresponding lanthanide thiolates (5 and 6) or selenolates (7 and 8) by elemental chalcogens concomitant with the (Me2N-o-C6H4CH2)2E2 (E = S or Se) release. Treatment of 3 and 4 with one equivalent or two equivalents of benzonitrile produces the serendipitous lanthanum and cerium-1-azaallyl complexes [η5-1,3-(Me3C)2C5H3]2Ln[N(H)C(Ph)═CHC6H4-o-NMe2] (Ln = La 13 and Ce 14) or amidine complexes [η5-1,3-(Me3C)2C5H3]2Ln[N(H)C(Ph)NC(Ph)═CHC6H4-o-NMe2]·C7H8 (Ln = La 15·C7H8 and Ce 16·C7H8), respectively. The compound 15 or 16 can also be readily synthesized by further insertion of one benzonitrile molecule into the 1-azaallyl complex 13 or 14. Insertion of N,N'-dicyclohexylcarbodiimide or phenyl isothiocyanate into Ln-C bonds within 3 and 4 results in the formation of the amidine complexes [η5-1,3-(Me3C)2C5H3]2Ln[CyNC(CH2C6H4-o-NMe2)NCy] (Cy = cyclohexyl, Ln = La 17 and Ce 18) or thioamidato complexes [η5-1,3-(Me3C)2C5H3]2Ln[SC(CH2C6H4-o-NMe2)NPh] (Ln = La 19 and Ce 20). All of the new compounds were characterized by various spectroscopic methods, and their solid-state structures were further confirmed by single-crystal X-ray diffraction analyses.


Anterior segment dysgenesis and the developmental glaucomas are complex traits.
Glaucoma refers to a heterogeneous group of disorders that involve retinal ganglion cell death, optic nerve damage, and loss of visual field. Glaucoma is a leading cause of vision loss worldwide, affecting an estimated 67 million people. Elevated intraocular pressure is a major risk factor for glaucoma. Individuals with malformations of structures of the anterior segment of the eye frequently develop elevated intraocular pressure and glaucoma. In this review, we focus on the developmental glaucomas, the subset of glaucomas associated with anterior segment dysgenesis. To minimize overlap with other reviews in this issue and elsewhere, we highlight the complex, multifactorial nature of these diseases and recent advances using mice.


Mitogen-activated protein kinase mediates epidermal growth factor-induced morphogenesis in pituitary GH3 cells.
Epidermal growth factor (EGF) causes pituitary GH3 cells to change from their normal predominantly rounded morphology to much more elongated cells with extensive filopodia, and this effect is accompanied by a parallel increase in cell volume. In view of this, and because EGF receptor expression is increased in some pituitary tumours, we examined the mechanism of this EGF-induced morphological effect as it may play a role in tumour invasiveness. The effect of treatment of the cells with EGF (1 nm, 4 days) was determined visually (expressed as percent non round cells) and by measuring the cell volume by Coulter Counter analysis. EGF treatment caused the cells to change their morphology with percent non round cells increasing from 37% in control cells to 74% in EGF-treated cultures; this was accompanied by a parallel increase in cell volume. Treatment of the cells with EGF in the presence of the MEK1 inhibitor (PD98059) completely blocked the EGF-induced morphological changes, showing that activation of the mitogen-activated protein kinase (MAPK) pathway is necessary to mediate this effect. Transfection of the cells with a constitutively activated mutant of MEK1 produced a similar morphological change to that produced by EGF treatment, with the proportion of non round cells increasing to 62% with a parallel increase in cell volume compared to cells transfected with the empty vector, demonstrating that direct activation of MAPK pathway is sufficient to mediate the observed morphological effects. The effects produced by activated MEK1 transfection could be blocked by PD98059. EGF had opposing effects on prolactin and growth hormone (GH) secretion by the cells, increasing prolactin release and inhibiting GH release. Transfection of the cells with activated MEK1 produced similar effects on hormone release as EGF treatment. In conclusion, the morphological effects of EGF on GH3 cells are mediated by activation of the MAPK pathway as blockade of this pathway abolished the observed effect, and direct activation of this pathway by transfection with an activated mutant of MEK1 was able to duplicate these effects. This mechanism may contribute to the growth and possibly local invasiveness of some pituitary tumours that express the EGF receptor.


Progression of Doppler changes in early-onset small for gestational age fetuses. How frequent are the different progression sequences?
To evaluate the progression of Doppler abnormalities in early-onset fetal smallness (SGA). A total of 948 Doppler examinations of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV), belonging to 405 early-onset SGA fetuses, were studied, evaluating the sequences of Doppler progression, the interval examination-labor at which Doppler became abnormal and the cumulative sum of Doppler anomalies in relation with labor proximity. The most frequent sequences were that in which only the UA pulsatility index (PI) became abnormal (42.1%) and that in which an abnormal UA PI appeared first, followed by an abnormal MCA PI (24.2%). In general, 71.3% of the fetuses followed the classical progression sequence UA→MCA→DV, mostly in the early stages of growth restriction (84.1%). In addition, the UA PI was the first parameter to be affected (9 weeks before delivery), followed by the MCA PI and the DV PIV (1 and 0 weeks). Finally, the UA PI began to sum anomalies 5 weeks before delivery, while the MCA and DV did it at 3 and 1 weeks before the pregnancy ended. In early-onset SGA fetuses, Doppler progression tends to follow a predictable order, with sequential changes in the umbilical, cerebral and DV impedances.


Biochemical composition and metabolic pathways of filarial worms Setaria cervi: search for new antifilarial agents.
The main problem regarding the chemotherapy of filariasis is that no safe and effective drug is available yet to combat the adult human filarial worms. Setaria cervi, the causal organism of setariasis and lumbar paralysis in cattle, is routinely employed as a model organism for conducting biochemical and enzymatic studies on filarial parasites. In view of the practical difficulties in procuring human strains of Wuchereria bancrofti and Brugia malayi for drug screening, the bovine filarial parasite S. cervi, resembling the human species in having microfilarial periodicity and chemotherapeutic response to known antifilarial agents, is widely used as a model in such studies. For a rational approach to antifilarial chemotherapy, knowledge of the biochemical composition and metabolic pathways of this helminth parasite may be of paramount importance, so that more potent antifilarial agents based on specific drug targets can be identified in drug discovery programmes. The present review provides an update on the biochemistry of the important metabolic pathways functioning within this potentially important bovine parasite, that have so far been studied, and on those that need to be investigated further so as to identify novel drug targets that can be exploited for designing new antifilarial drugs.


The min locus, which confers topological specificity to cell division, is not involved in its coupling with nucleoid separation.
In Escherichia coli, nucleoid separation and cell constriction remain tightly linked when division is retarded by altering the level of synthesis of the protein FtsZ. In this study, we have examined the role of the min locus, which is responsible for the inactivation of polar division sites, in the partition-septation coupling mechanism. We conclude that the coupling persists in a delta min strain and that its timing relative to replication remains dependent on the level of FtsZ synthesis. We suggest that the retarded nucleoid segregation observed in min mutants is the result of this coupling in cells with a perturbed pattern of nonpolar divisions.


[Refractory generalized convulsions in a patient undergoing brain tumor resection during propofol anesthesia].
Propofol has been used to treat convulsions, while the drug is known to induce convulsions. We described a case of generalized convulsions during brain tumor resection under propofol anesthesia. A 24-year-old man was scheduled to undergo brain tumor resection. He had no history of epilepsy. Anesthesia was induced and maintained with propofol and fentanyl. During the craniotomy, the patient developed generalized convulsions. Diazepam, thiamylal, and phenytoin were given intravenously and the seizure activity resolved. Generalized convulsions recurred three times during the operation. Postoperative course was uneventful. On the 16 th postoperative day, the patient underwent ventriculoperitoneal shunt under general anesthesia using sevoflurane, nitrous oxide and oxygen. Convulsions were not noted intra- and postoperatively. Because convulsions did not occur during sevoflurane anesthesia and the patient had no history of epilepsy, propofol may have induced a generalized convulsions on the first operation.


Rapid freezing of deep cerebral structures for electron microscopy.
A method is described for the investigation of deep cerebral structures by freeze-substitution. The head of a mouse is sectioned in a guillotine-like apparatus. The exposed surface is subjected to freeze-substitution. Electron micrographs prepared from this material exhibit under a layer of sheared tissue, a layer of tissue comparable with that observed previously in micrographs of the cerebral and cerebellar cortices subjected to freeze-substitution of their natural surfaces. By varying the plane in which the head is sectioned any structure in the brain can be made accessible to freeze-substitution.


[Palliative therapy concepts for pancreatic carcinoma].
The majority of patients with ductal pancreatic adenocarcinoma are already in a locally advanced or metastatic stage at the time of diagnosis and require palliative therapy. Interventional and operative measures are available for the restoration of biliary outflow in bile duct obstruction and the continuity of the upper intestinal lumen in duodenal or gastric outlet obstruction. In the presence of tumor-related pain, pain therapy according to the World Health Organization (WHO) scheme or a truncus coeliacus blockade, in cachexia a nutritional therapy and in thromboembolic events an anticoagulant therapy are used. An individualized palliative chemotherapy regimen should be selected for each patient, taking into account the patient's general condition and the side effects profile of the chemotherapeutic agents. Radiochemotherapy and local ablative therapies should currently only be used within the framework of studies. A palliative resection is not recommended according to current knowledge.


Alemtuzumab in T-cell malignancies.
Alemtuzumab is a humanized monoclonal antibody directed against the CD52 antigen, which is abundantly expressed on all normal and most malignant T-lymphocytes. We summarize the results of our experience using alemtuzumab to treat a range of clinically aggressive, mature, post-thymic, T-cell malignancies, including T-cell prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), T-cell large granular lymphocyte (T-LGL) leukemia, and human T-cell lymphotropic virus I (HTLV-I) associated adult T-cell leukemia-lymphoma (ATLL). Alemtuzumab was administered at a dose of 30 mg, three times a week until maximum response. Apart from first-dose reactions, which were common, treatment was well tolerated, the main complication being infection and viral reactivation associated with the prolonged lymphopenia. Overall response rates were 76% (60% complete response) in 39 patients with T-PLL and 100% in 3 patients with CTCL, of duration up to 4 yr. Experience in T-LGL and ATLL is limited to single cases only and further studies are required to better define the role of alemtuzumab in these subgroups. Our results indicate that alemtuzumab has activity in T-cell malignancies, particularly in T-PLL and in patients with predominantly blood and bone marrow disease. It may be possible to prolong response duration by the use of high-dose therapy and stem cell transplantation. Alemtuzumab may also have a role in purging minimal residual disease following other chemotherapy and prior to transplantation. We conclude that treatment with alemtuzumab may offer new hope to patients who otherwise have a bleak prognosis.


Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma.
It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro. The expression of CXCL1 in cancer cells was correlated with T invasion (T2-T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2-T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients. The expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.


Variability in aflatoxin B(1)-macromolecular binding and relationship to biotransformation enzyme expression in human prenatal and adult liver.
Studies of transplacental transfer of aflatoxin B(1) (AFB(1)) suggest that the developing human fetus may be a sensitive target for AFB(1) injury. Because AFB(1) requires metabolic activation to the reactive AFB(1)-8,9-exo-epoxide (AFBO) to exert its carcinogenic effects, ontogenic and interindividual differences in AFB(1) biotransformation enzymes may underlie susceptibility to AFB(1)-induced cell injury. The present study was initiated to compare the rates of in vitro AFB(1)-DNA and AFB(1)-protein adduct formation among a panel of 10 adult and 10 second-trimester prenatal livers and to examine the relationship among AFB(1) metabolizing enzyme expression and AFB(1) binding. Mixtures of cytosolic and microsomal proteins from prenatal and adult livers catalyzed the formation of AFB(1)-DNA and AFB(1)-protein adducts at relatively similar rates, although greater individual variability in AFB(1) adduct formation was observed in adult tissues. Extensive interindividual variation among adult tissues was observed in the expression of the AFB(1) activation enzymes cytochrome P4501A2 (CYP1A2), CYP3A4/5, and lipoxygenase (LO). Prenatal CYP3A7 expression was also highly variable. LO expression was eightfold higher in prenatal liver tissues than adults, whereas the expression of the AFBO detoxification enzyme microsomal epoxide hydrolase was twofold higher in adult liver. The levels of the polymorphic glutathione S-transferase M1 (hGSTM1-1), which may potentially protect against AFBO injury, were higher in the hGSTM1-1-expressing tissues of adults in relation to prenatal livers. In general, there was not a strong relationship among AFB(1)-DNA or AFB(1)-protein adduct formation and expression levels of individual AFB(1) metabolizing enzymes. In summary, despite the presence of marked individual and ontogenic differences in the expression of AFB(1) metabolizing enzymes, human second trimester prenatal liver tissues compared to adults do not exhibit a marked sensitivity to the in vitro formation of macromolecular AFB(1) adducts.


Bending strength of zirconia/porcelain functionally graded materials prepared using spark plasma sintering.
The purpose of this study was to fabricate functionally graded materials (FGMs) consisting of yttria-stabilised tetragonal zirconia polycrystal (Y-TZP) and porcelain using spark plasma sintering (SPS) and examine the influence of their microstructures and thermal stress on their bending strengths. Two types of four-layered Y-TZP/porcelain FGMs having a constant layer thickness and a varying layer thickness, Y-TZP/porcelain composite materials having a microstructure corresponding to each layer in FGMs and monolithic materials of Y-TZP and porcelain were fabricated by SPS. The Y-TZP/porcelain volume fraction of each layer in FGMs was varied over 100/0-70/30. Three-point bending test, X-ray diffraction, density measurement, microstructure observation, and thermal stress estimation were performed to characterise the materials. The bending strength of the Y-TZP/porcelain composite materials decreased with the volume fraction of the porcelain. About FGMs, when the 100%Y-TZP layer was on the tensile stress side during the bending test, the bending strength was almost the same as that of the 100%Y-TZP monolithic material. On the other hand, when the 100%Y-TZP layer was on the compressive stress side, the bending strength of FGM having a constant layer thickness was almost the same as that of the 70%Y-TZP+30%porcelain composite material, while the bending strength of FGM with a varying layer thickness was significantly higher than that of the 70%Y-TZP+30%porcelain composite material. The FGMs prepared and analyzed in this research can potentially be used for crowns and bridges as well as for inlays and onlays. The SPS method could effectively fabricate the Y-TZP/porcelain FGMs, and the bending strength results revealed that the graded structure was very efficient to raise the bending strength.


In vivo genotoxicity of mercury chloride and lead acetate: Micronucleus test on acridine orange stained fish cells.
The genotoxic effects of mercury chloride and lead acetate were evaluated in vivo using the micronucleus (MN) assay on acridine-orange (AO) stained peripheral blood erythrocytes, gill and fin epithelial cells of Carassius auratus auratus. Fish were exposed to three different concentrations of mercury chloride (MC) (1 microg/, 5 microg/L and 10 microg/L) and lead acetate (LA) (10 microg/L, 50 microg/L and 100 microg/L) for 2, 4 and 6 days. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear buds (NBs) were assessed in the erythrocytes. The ratio of polychromatic and normochromatic erythrocytes (PCE/NCE) in peripheral blood was also evaluated to assess cytotoxicity. MN frequencies in all three tissues were elevated in fish exposed to both LA and MC. However, NBs showed different sensitivity to metal treatments. MN frequencies in both control and treated fish were highest in gill cells and generally lower in erythrocytes and fin cells. PCE/NCE rations decreased in relation to MC and LA treatments. The results of this study indicate that LA and MC have genotoxic and cytotoxic damage in fish and confirmed that AO staining is a suitable technique for in vivo MN test in fish.


Residential distance to major roadways and cardiac structure in African Americans: cross-sectional results from the Jackson Heart Study.
Heart failure (HF) is a significant source of morbidity and mortality among African Americans. Ambient air pollution, including from traffic, is associated with HF, but the mechanisms remain unknown. The objectives of this study were to estimate the cross-sectional associations between residential distance to major roadways with markers of cardiac structure: left ventricular (LV) mass index, LV end-diastolic diameter, LV end-systolic diameter, and LV hypertrophy among African Americans. We studied baseline participants of the Jackson Heart Study (recruited 2000-2004), a prospective cohort of cardiovascular disease (CVD) among African Americans living in Jackson, Mississippi, USA. All cardiac measures were assessed from echocardiograms. We assessed the associations between residential distance to roads and cardiac structure indicators using multivariable linear regression or multivariable logistic regression, adjusting for potential confounders. Among 4826 participants, residential distance to road was <150 m for 103 participants, 150-299 m for 158, 300-999 for 1156, and ≥1000 m for 3409. Those who lived <150 m from a major road had mean 1.2 mm (95% CI 0.2, 2.1) greater LV diameter at end-systole compared to those who lived ≥1000 m. We did not observe statistically significant associations between distance to roads and LV mass index, LV end-diastolic diameter, or LV hypertrophy. Results did not materially change after additional adjustment for hypertension and diabetes or exclusion of those with CVD at baseline; results strengthened when modeling distance to A1 roads (such as interstate highways) as the exposure of interest. We found that residential distance to roads may be associated with LV end-systolic diameter, a marker of systolic dysfunction, in this cohort of African Americans, suggesting a potential mechanism by which exposure to traffic pollution increases the risk of HF.


NMR basis for interprotein electron transfer gating between cytochrome c and cytochrome c oxidase.
The final interprotein electron transfer (ET) in the mammalian respiratory chain, from cytochrome c (Cyt c) to cytochrome c oxidase (CcO) is investigated by (1)H-(15)N heteronuclear single quantum coherence spectral analysis. The chemical shift perturbation in isotope-labeled Cyt c induced by addition of unlabeled CcO indicates that the hydrophobic heme periphery and adjacent hydrophobic amino acid residues of Cyt c dominantly contribute to the complex formation, whereas charged residues near the hydrophobic core refine the orientation of Cyt c to provide well controlled ET. Upon oxidation of Cyt c, the specific line broadening of N-H signals disappeared and high field (1)H chemical shifts of the N-terminal helix were observed, suggesting that the interactions of the N-terminal helix with CcO are reduced by steric constraint in oxidized Cyt c, while the chemical shift perturbations in the C-terminal helix indicate notable interactions of oxidized Cyt c with CcO. These results suggest that the overall affinity of oxidized Cyt c for CcO is significantly, but not very much weaker than that of reduced Cyt c. Thus, electron transfer is gated by dissociation of oxidized Cyt c from CcO, the rate of which is controlled by the affinity of oxidized Cyt c to CcO for providing an appropriate electron transfer rate for the most effective energy coupling. The conformational changes in Lys13 upon CcO binding to oxidized Cyt c, shown by (1)H- and (1)H, (15)N-chemical shifts, are also expected to gate intraprotein ET by a polarity control of heme c environment.


Acute myelomonocytic leukemia after irradiation and chemotherapy for Ewing's sarcoma.
A case is presented in which the diagnosis of acute myelomonocytic leukemia was made 16 months after the start of irradiation and chemotherapy for Ewing's sarcoma. The association of these two diseases is rare. The etiologic role of therapy in the development of leukemia is speculative in this case. However, there is need for surveillance for secondary neoplasms of all types so that the benefits of therapy may be properly weighed against the risks.


Interaction in vitro between synovial cells and autologous lymphocytes and sera from arthritis patients.
Synovial cells from patients with rheumatoid arthritis (RA) when grown in vitro in media supplemented with 20% fetal calf serum failed to show any difference in growth rate, life span, uptake of tritiated thymidine or cellular and nuclear characteristics when compared with synovial cells from patients with osteoarthritis or other joint diseases grown similarly in 20% serum enriched medium. There was also no evidence that lymphocytes and/or sera from RA patients were more cytotoxic to autologous synovial cells than sera and/or lymphocytes from OA patients. It is unlikely that antisynovial antibodies or lymphocytes from RA patients act as triggers for synovial damage.


Parotid tumors: fine-needle aspiration and/or frozen section.
The purpose of this study was to analyze and compare the value of fine-needle aspiration cytology (FNAC) and frozen section (FS) analysis in the assessment of parotid gland tumors. Chart review and cross-sectional analysis. FNAC and FS analysis of 110 parotid tumors, 68 malignancies and 42 benign tumors, were analyzed and compared with the final histopathologic diagnosis. The accuracy, sensitivity, and specificity of FNAC in detecting malignant tumors were 79 percent, 74 percent, and 88 percent, respectively. On FS analysis, the accuracy, sensitivity, and specificity in detecting malignant tumors were 94 percent, 93 percent, and 95 percent, respectively. The histologic tumor type was correctly diagnosed by FNAC and FS in 27 of 42 (64%) and 39 of 42 (93%) benign tumors, respectively, and in 24 of 68 (35%) and 49 of 68 (72%) malignant neoplasms, respectively. The current analysis showed a superiority of FS compared with FNAC regarding the diagnosis of malignancy and tumor typing. FNAC alone is not prone to determine the surgical management of parotid malignancies.


Granulocyte-macrophage colony-stimulating factor enhances effect of temozolomide on high-grade glioma cells.
In the present study, to delve into the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with temozolomide (TMZ) on high-grade glioma cells and related mechanism, six cases of high-grade glioma cells from patient's tumor tissues were cultured. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay was performed to detect cell proliferation and toxicity. Flow cytometry was performed to ascertain cell cycle and apoptosis rate. To detect the expressions of O6-methylguanine-DNA methyltransferase (MGMT) methylation status and MGMT protein, respectively, specific PCR and immunofluorescence were performed. According to the results of MTT assay, compared with the results of control group, GM-CSF group exhibited enhanced cell viability in varying degrees. In three cases of cells (MGMT gene methylation), the combination group [(67.67 ± 1.16), (68.13 ± 1.06), (68.42 ± 1.73)] had noticeably lower cell viability than the corresponding TMZ group [(90.00 ± 1.73), (82.33 ± 1.53), (82.67 ± 2.11)] (P < 0.01). Nevertheless, the two groups showed no significant difference in another three cases (MGMT gene unmethylated) (P > 0.05). In combination group, the apoptosis rate of the MGMT methylation cells was higher than that in the corresponding TMZ group (P < 0.01), which is consistent with MTT assay results. In all six cases of primary glioma cells, the fraction of cells in G1 phase of GM-CSF-treated group was noticeably down-regulated and was up-regulated in S phase (P < 0.01). GM-CSF could induce high-grade glioma cells to rapidly enter the cell cycle, thereby enhancing the lethal effect of TMZ on glioma cells with MGMT gene promoter methylation. However, this effect is not ideal on glioma cells with MGMT unmethylation.


Integrative multi-omics analysis of three early diverged rosid species reveals an ancient hierarchical cold-responsive regulatory network.
Elucidating regulators, including transcription factors (TFs) and RNA-binding proteins (RBPs), underlying gene transcriptional and post-transcriptional co-regulatory network is key to understand plant cold responses. Previous studies were mainly conducted on single species, and whether the regulators are conserved across different species remains elusive. Here, we selected three species that diverged at the early evolution of rosids (~99-113 million years ago), performed cold-responsive phylotranscriptome experiments, and integrated chromatin immunoprecipitation- and DNA affinity purification-sequencing (ChIP/DAP-seq) analysis to explore cold-responsive regulators and their regulatory networks. First, we detected over 10,000 cold-induced differentially expressed genes (DEGs) and alternative splicing genes (DASGs) in each species. Among the DEGs, a set of TFs and RBPs were conserved in rosid cold response. Compared to TFs, RBPs displayed a delayed cold-responsive pattern, implying a hierarchical regulation of DEGs and DASGs. By integrating DEGs and DASGs, we identified 259 overlapping DE-DASG orthogroups (closely-related homologs) that were cold-regulated at both transcriptional and post-transcriptional levels in all three studied species. Notably, pathway analysis on each of the DEGs, DASGs, and DE-DASGs in the three species showed a common enrichment connected to the circadian rhythm. Evidently, 226 cold-responsive genes were directly targeted by at least two circadian rhythm components (CCA1, LHY, RV4, RVE7, and RVE8). Finally, we revealed an ancient hierarchy of cold-responsive regulatory networks at transcriptional and post-transcriptional levels launched by circadian components in rosids. Altogether, this study sheds light on conserved regulators underlying cold-responsive regulatory networks across rosid species, despite a long evolutionary history after their divergence.