Cross-regulatory interactions among tracheal genes support a co-operative model for the induction of tracheal fates in the Drosophila embryo.
The Drosophila tracheal system arises from clusters of ectodermal cells that invaginate and migrate to originate a network of epithelial tubes. Genetic analyses have identified several genes that are specifically expressed in the tracheal cells and are required for tracheal development. Among them, trachealess (trh) is able to induce ectopic tracheal pits and therefore it has been suggested that it would act as an inducer of tracheal cell fates; however, this capacity appears to be spatially restricted. Here we analyze the expression of the tracheal specific genes in the early steps of tracheal development and their cross-interactions. We find that there is a set of primary genes including trh and ventral veinless (vvl) whose expression does not depend on any other tracheal gene and a set of downstream genes whose expression requires different combinations of the primary genes. We also find that the combined expression of primary genes is sufficient to induce some downstream genes but not others. These results indicate that there is not a single master gene responsible for the appropriate expression of the tracheal genes and support a model where tracheal cell fates are induced by the co-operation of several factors rather than by the activity of a single tracheal inducer.


Chronic venous insufficiency: A review for nurses.
Chronic venous insufficiency (CVI) is a potentially debilitating disorder associated with serious complications such as lower extremity venous ulcers. This article reviews the incidence and pathophysiology of CVI, nursing assessment, diagnosis and interventions, and patient education needed to manage the disease and prevent complications.


Phosphaturic mesenchymal tumor with symptoms related to osteomalacia that appeared one year after tumorectomy.
A 45-year-old man was admitted to our hospital because of bone pain and hypophosphatemia. He had undergone surgery 2 years previously for a "benign unclassified mesenchymal tumor" in the skull, but there were no clinical symptoms related to osteomalacia. His laboratory examination revealed low serum phosphate, high alkaline phosphatase, and normal calcium levels. The diagnosis of tumor-induced osteomalacia due to phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) was made by re-examining the pathologic specimens. Oral supplementation with phosphate and 1-25-dihydroxyvitamin D relieved his clinical symptoms and laboratory values returned to normal. However, subcutaneous administration of octreotide had no clinical effect. Clinicians and pathologists should be aware of the existence of PMTMCT especially nonphosphaturic or asymptomatic variants of this disorder.


Copper-catalyzed trifluoromethylthiolation of primary and secondary alkylboronic acids.
A Cu-catalyzed trifluoromethylthiolation of primary and secondary alkylboronic acids with an electrophilic trifluoromethylthiolating reagent is described. Tolerance for a variety of functional groups was observed.


Development and Characterization of PA 450 and PA 3282 Epoxy Coatings as Anti-Corrosion Materials for Offshore Applications.
The optimization of two different types of hardeners, namely polyaminoamine adduct (Aradur 450 BD) and polyamidoamine adduct (Aradur 3282 BD), with diglycidyle ether of bisphenol-A (DGEBA) epoxy resin was carried out. Three different stoichiometries of PA 450 to the epoxy resin to fabricate E-0, E-1, and E-2 coating samples and the other three of PA 3282 to the epoxy resin to fabricate F-0, F-1, and F-2 coating samples were coated on mild steel panels. All coated samples were characterized by scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), and nanoindentation techniques. The electrochemical corrosion behavior of the fabricated coatings was investigated using electrochemical impedance spectroscopy (EIS) after various exposures in the climatic conditions in 3.5% NaCl solutions. It was found that the coatings possess almost identical thermal and mechanical properties. Moreover, the E-1 coating shows better corrosion resistance compared to E-0 and E-2 coatings. On the other hand, the F-1 coating was the most effective in significantly improving corrosion resistance. Overall, the addition of PA 450 and PA 3282 to some stoichiometries improves the corrosion resistance of the fabricated coatings.


The modifier protein of glyceraldehyde-3-phosphate dehydrogenase reduces free radical-mediated renal damage in a rat model of acute kidney injury.
The modifier protein (MP) of glyceraldehyde-3-phosphate dehydrogenase has been shown to promote growth of renal epithelial cells in vitro. The aim of this study was to show the in vivo effects of MP in a rat model of gentamicin-induced acute kidney injury (AKI). MP was purified from monkey renal tubular epithelial cell line BSC-1 and confirmed by amino acid sequencing. Male Sprague-Dawley rats were divided into the following groups: normal control, gentamicin-treated, epidermal growth factor (EGF) plus gentamicin-treated, and MP plus gentamicin-treated, as well as control groups for EGF and MP alone. Levels of serum creatinine (SCr), serum and tissue lipid peroxide, nitric oxide and glutathione-S-hydrogenase for each group were measured on the 7th and 14th days of treatment. Tissue sections were studied with light microscopy. The gentamicin-treated group showed a marked increase in SCr compared to the normal control group. Co-treatment of gentamicin with MP and/or EGF produced similar significant decreases preventing the increase in SCr. There were also significant reductions in serum and tissue homogenate levels of lipid peroxide and nitric oxide, accompanied by an increase in the level of glutathione-S-hydrogenase, in the MP co-treated groups compared to the gentamicin-treated group. AKI was confirmed histologically in the gentamicin-treated group, with damage to the tubular epithelium recorded. This was attenuated by MP co-treatment. There were also reductions in the expression of intercellular adhesion molecule-1 and proliferating cell nuclear antigen in the MP co-treated groups. Using a gentamicin model of AKI, MP was able to reduce free radical production in kidney tissue and in the circulation, thus preventing oxidant injury and minimizing damage in renal epithelial cells.


Gestational and early postnatal exposure to simulated high altitude does not modify postnatal body mass growth trajectory in the rat.
Postnatal hypoxia blunts body mass growth. It is also known that the quality of the fetal environment can influence the subsequent adult phenotype. The main purpose of the study was to determine whether gestational hypoxia and early postnatal hypoxia are able to blunt growth when the offspring is raised under normoxia. Hypobaric hypoxia was induced in simulated high altitude (SHA) chambers in which air was maintained at 380 mmHg (5450 m). Mature Sprague-Dawley rats of both sexes were divided in normoxic (NX) and hypoxic (HX) groups and, in the case of the HX group, maintained for 1 month at 5450 m. Mating was then allowed under NX or HX conditions. Offspring were NX-NX, NX-HX, HX-HX, or HX-NX: the first term indicates NX or HX during both gestation and the first 30 days of life; the second term indicates NX or HX during postnatal life between days 30 and 133. Body mass (g) was measured periodically and body mass growth rate (BMGR, g/d) was estimated between days 33 and 65 of postnatal life. Results can be summarized as follows: 1) BM was significantly higher in NX than in HX rats at weaning; 2) BMGR was not significantly different between NX-NX and HX-NX rats, and between HX-HX and NX-HX animals; and 3) BMGR was significantly higher in rats living under NX conditions than in those living under HX conditions during postnatal life. Data suggest that that hypobaric hypoxia during gestational and early postnatal development of rats does not alter the regulation of body mass growth in rats when compared to that seen under sea-level conditions.


Effects of the healing activity of rosemary-of-Chapada (Lippia gracilis Schauer) on cutaneous lesions in rats.
To evaluate the effects of rosemary leaf essential oil-based ointments on the healing of rat skin lesions. Sixty adult male rats, with dorsal excisional skin wounds made surgically under anesthesia, were divided into three groups (n = 20): Sham group (untreated wounds); control group (CG, wounds treated with vehicle); and essential oil (EO) treated group (wounds treated with essential oil-based ointments), administered topically once daily. Skin wounds were evaluated at 4, 7, 14, and 21 days after EO or vehicle treatments. Lesions were analyzed macroscopically for the contraction degree. Formalin-fixed paraffin-embedded sections of skin wounds were used for histopathological evaluation. Macroscopic evaluation showed wounds edges with thin crust without firmness and yellowish color, along with an improvement in wound contraction in EO group when compared to the other groups. A reduced inflammatory reaction, along with newly formed small diameter capillaries and more organized and elongated collagen fibers, were more frequently observed in EO group than in the other groups. Moreover, blood vessel number and collagen fibers density were significantly higher in EO group. Skin lesion treatment with rosemary leaf essential oil-based ointments accelerates the initial stages of healing, reduces inflammation, and increases angiogenesis, collagen fibers density, and wound contraction in rats.


Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.
Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. To assess the effectiveness and safety of late initiation of EPO (initiated at eight days after birth or later) in reducing the use of red blood cell (RBC) transfusions in preterm and/or low birth weight infants. For this update MEDLINE, EMBASE, CINAHL, and The Cochrane Library were searched in March 2012. Additional searches included the Pediatric Academic Societies Annual Meetings from 2000 to 2012 (Abstracts2 View(TM)) and clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp). Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at ≥ eight days of age) versus placebo or no intervention in preterm (< 37 weeks) and/or low birth weight (< 2500 g) neonates. Data collection and analyses were performed in accordance with the methods of the Cochrane Neonatal Review Group. In this 2012 update one new study for inclusion was identified. Twenty-eight studies enrolling 1361 preterm infants in 21 countries were included. Most trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions [typical risk ratio (RR); 0.66 (95% confidence interval (CI); 0.59 to 0.74); typical risk difference (RD) -0.21 (95% CI; -0.26 to -0.16); typical number needed to benefit (NNTB) of 5 (95% CI 4 to 6) 19 studies, 912 infants]. There was moderate heterogeneity for this outcome [for RR (P < 0.00001; I(2) = 74.0%); for RD (P = 0.0006; I(2) = 58.9%)]. Similar results were obtained in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. In this update there was no significant reduction in the total volume (mL/kg) of blood transfused per infant [typical MD -1.61mL/kg (95% CI -5.78 to 2.57); 5 studies, 197 infants] There was high heterogeneity for this outcome (P = 0.00001, I(2) = 92%). There was a significant reduction in the number of transfusions per infant (nine studies enrolling 567 infants); [typical MD -0.78 (-0.97 to -0.59)]. Three studies including 331 patients reported on retinopathy of prematurity (ROP) (all stages), with a typical RR 0.79 (95% CI 0.57 to 1.10) and a typical RD of -0.05 (95% CI -0.13 to 0.02). This outcome was not statistically significantly different between the groups. There was no heterogeneity for this outcome for either RR (P = 0.41; I(2) = 0%) or RD (P = 0.43; I(2) = 0%). Two trials enrolling 212 patients reported on severe ROP (stage 3 or greater). The typical RR was 0.83 (95% CI 0.23 to 2.98) and the typical RD was -0.01 (95% CI -0.06 to 0.05); neither were statistically significant. There was no heterogeneity for this outcome for either RR (P = 0.29; I(2) = 9.3%) or RD (P = 0.36; I(2) = 0%).There were no significant differences in other clinical outcomes. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant but not the total volume of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes. Further research of the use of late EPO treatment to prevent donor exposure is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment.


A reassessment of leptin's role in triggering the onset of puberty in the rat and mouse.
Leptin is an adipocyte-derived hormone that has been implicated to serve as a metabolic signal to the reproductive axis. The role of leptin in pubertal maturation, however, has been a much-debated topic. We have previously reported that leptin serves as a permissive signal to the onset of puberty in the female rat. In an attempt to further understand the mechanics of leptin during pubertal maturation in rodent species, we had three experimental objectives: first, to describe the temporal relationship of leptin with development in the male and female rat; second, to seek evidence for an increase in responsiveness of the neuroendocrine axis to leptin by assessing for possible changes in leptin receptor expression during pubertal developmental in the female rat; and, third, to reevaluate the possible role of leptin as a permissive signal to the onset of puberty in the mouse. We found that serum leptin levels remain relatively constant during the prepubertal and postpubertal stages of both sexes. In addition, we could not detect any significant developmental changes in leptin receptor gene expression in the hypothalamus of the female rat. Lastly, we corroborated our findings in the female rat that leptin reversed the delay in pubertal maturation secondary to food restriction but did not advance the onset of puberty in female mice. Together, these results suggest that leptin is not a metabolic trigger for the onset of puberty in the rodent; instead, leptin is one of several permissive factors, whose presence may be necessary but alone is not sufficient to initiate sexual maturation in these species.


Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005.
Philadelphia-chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate-dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1-18years were enrolled in three consecutive ALL/SHOP trials (SHOP-94/SHOP-99/SHOP-2005). In the SHOP-2005 trial, imatinib (260mg/m(2) per day) was given on day-15 of induction. Allogeneic haematopoietic stem-cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty-three patients were evaluable (22 boys, median age 6·8years, range, 1·2-15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non-imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow-up of 109 and 39months for the non-imatinib and imatinib cohorts, the 3-year event-free survival (EFS) was 29·6% and 78·7%, respectively (P=0·01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL.


Reconfigurable all-optical on-chip MIMO three-mode demultiplexing based on multi-plane light conversion.
We present, to the best of our knowledge, the first experimental demonstration of reconfigurable all-optical on-chip multi-input-multi-output three-mode demultiplexing based on multi-plane light conversion. The demultiplexer consists of cascaded phase shifter arrays and multimode interference couplers integrated on a compact silicon chip. By optimizing the phase shifters, reconfigurable three-mode demultiplexing is experimentally realized with wavelength-dependent loss of less than 3 dB and modal crosstalk of less than -10 dB over a 23 nm optical bandwidth. Error-free mode demultiplexing of 40 Gbps non-return-to-zero signal is also demonstrated.


Dynamic Regulation of Mitochondrial [Ca2+] in Hippocampal Neurons.
While neuronal mitochondria have been studied extensively in their role in health and disease, the rules that govern calcium regulation in mitochondria remain somewhat vague. In the present study using cultured rat hippocampal neurons transfected with the mtRCaMP mitochondrial calcium sensor, we investigated the effects of cytosolic calcium surges on the dynamics of mitochondrial calcium ([Ca2+]m). Cytosolic calcium ([Ca2+]c) was measured using the high affinity sensor Fluo-2. We recorded two types of calcium events: local and global ones. Local events were limited to a small, 2-5 µm section of the dendrite, presumably caused by local synaptic activity, while global events were associated with network bursts and extended throughout the imaged dendrite. In both cases, cytosolic surges were followed by a delayed rise in [Ca2+]m. In global events, the rise lasted longer and was observed in all mitochondrial clusters. At the end of the descending part of the global event, [Ca2+]m was still high. Global events were accompanied by short and rather high [Ca2+]m surges which we called spikelets, and were present until the complete decay of the cytosolic event. In the case of local events, selective short-term responses were limited to the part of the mitochondrial cluster that was located directly in the center of [Ca2+]c activity, and faded quickly, while responses in the neighboring regions were rarely observed. Caffeine (which recruits ryanodine receptors to supply calcium to the mitochondria), and carbonyl cyanide m-chlorophenyl hydrazine (CCCP, a mitochondrial uncoupler) could affect [Ca2+]m in both global and local events. We constructed a computational model to simulate the fundamental role of mitochondria in restricting calcium signals within a narrow range under synapses, preventing diffusion into adjacent regions of the dendrite. Our results indicate that local cytoplasmic and mitochondrial calcium concentrations are highly correlated. This reflects a key role of signaling pathways that connect the postsynaptic membrane to local mitochondrial clusters.


The epidemiology of upper airway injury in patients undergoing major surgical procedures.
Airway injury is a potentially serious and costly adverse event of anesthesia care. The epidemiologic characteristics of airway injury have not been well documented. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) is a multicenter, prospective, outcome-oriented database for patients undergoing major surgical procedures. Using the NSQIP data for the years 2005 to 2008, we examined the incidence of, and risk factors for, airway injury. Of the 563,190 patients studied, 1202 (0.2%) sustained airway injury. The most common airway injury was lip laceration/hematoma (61.4%), followed by tooth injury (26.1%), tongue laceration (5.7%), pharyngeal laceration (4.7%), and laryngeal laceration (2.1%). Multivariable logistic modeling revealed an increased risk of airway injury in patients with Mallampati class III (adjusted odds ratio [OR], 1.69; 99% confidence interval [CI], 1.36-2.11, relative to patients with Mallampati classes I and II) or class IV (adjusted OR, 2.6; 99% CI, 1.52-4.02), and in patients aged 80 years or older (adjusted OR, 1.50; 99% CI, 1.02-2.19, relative to patients aged 40 to 49 years). The risk of airway injury for patients undergoing major surgical procedures is approximately 1 in 500. Patients with difficult airways as indicated by Mallampati classes III and IV are at significantly increased risk of sustaining airway injury during anesthesia for major surgical procedures.


A phage display screen and binding studies with acetylated low density lipoprotein provide evidence for the importance of the scavenger receptor cysteine-rich (SRCR) domain in the ligand-binding function of MARCO.
MARCO is a class A scavenger receptor capable of binding both gram-negative and -positive bacteria. Using the surface plasmon resonance technique, we show here that a recombinant, soluble form of MARCO, sMARCO, binds the major gram-negative and -positive bacterial surface components, lipopolysaccharide and lipoteichoic acid. Yet, the interaction of these two polyanions with sMARCO is of much lower affinity than that of polyinosinic acid, a polyanionic inhibitor of bacterial binding to MARCO. To further elucidate the ligand-binding functions of MARCO, we performed a phage display screen with sMARCO. The screening resulted in the enrichment of only a handful of phage clones. Contrary to expectations, no polyanionic peptides, but only those with a predominantly hydrophobic nature, were enriched. One peptide, VRWGSFAAWL, was displayed on two-thirds of the phages recovered after four rounds of screening. The VRWGSFAAWL phage-sMARCO interaction had significantly slower dissociation kinetics than that between sMARCO and lipopolysaccharide or lipoteichoic acid. Further work with this phage, and the second most enriched phage, displaying the peptide RLNWAWWLSY, demonstrated that both peptides bind to the SRCR domain of MARCO, and that they probably bind to the same site. Data base searches suggested that the VRWGSFAAWL peptide represents complement component C4, but we could not convincingly confirm this suggestion. A study with chimeric scavenger receptors indicated that even minor sequence changes in the MARCO scavenger receptor cysteine-rich (SRCR) domain can have profound effects on the binding of the prototypic scavenger receptor ligand, acetylated low density lipoprotein. As shown by differential binding of glutathione S-transferase-VR-WGSFAAWL, these differences were very likely due to conformational changes. These findings led to experiments that demonstrated a crucial role of the SRCR domain for acetylated low density lipoprotein binding in MARCO. Thus, our results strengthen the notion that the SRCR domain is the major ligand-binding domain in MARCO. Furthermore, they suggest that the domain may contain multiple ligand-binding sites.


Predictive value of p53 expression in the risk of malignant gastrointestinal stromal tumors: Evidence from 19 studies.
The current published data on p53 expression and its predictive value in the risk of malignant gastrointestinal stromal tumors (GIST) has are inconclusive. To derive a more precise estimation of the correlation between p53 and the biological behavior of GIST, a meta-analysis was performed. Studies were identified by searching PubMed and Embase. Inclusion criteria were GIST patients, and the evaluation of p53 expression and risk of malignancy. The odds ratio (OR) for a positive rate of p53 in the benign group vs. that in the malignant group and the ORs for the positive rate of p53 in the National Institutes of Health (NIH) very low risk + low risk group (VL+L) vs. the NIH intermediate risk + high risk (I+H) group were calculated with a 95% confidence interval (CI) for each study as an estimation of the predictive value of p53. A total of 19 studies including 1163 patients were involved in this meta-analysis. The overall OR for the positive rate of p53 in the malignant group vs. the benign group revealed that significantly elevated risks of positive p53 in the malignant group were achieved (OR 0.14, 95% CI: 0.06-0.31, P<0.00001, P(heterogeneity)=0.86). Moreover, significantly elevated risks of correlation between p53 expression and the NIH I+H group were achieved in the comparison of the NIH VL+L group vs. the NIH I+H group (OR, 0.25; 95% CI, 0.17-0.38; P<0.00001, P(heterogeneity)=0.04). The results indicate that p53 expression correlates with poor prognosis in GIST and has a close relationship within the NIH I+H group.


Long-term air pollution levels modify the relationships between short-term exposure to meteorological factors, air pollution and the incidence of hand, foot and mouth disease in children: a DLNM-based multicity time series study in Sichuan Province, China.
Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51-1.17) in the 90th percentile of SO2 (19.6 μg/m3) and 0.41 (95% CI: 0.27-0.64) in the 10th percentile of SO2 (10.6 μg/m3). Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.


[Some psychological and emotional aspects of retirement in physicians: a first approach].
Retirement is a time of life marked by many social prejudices. However, links of retirement to depression do not have any scientific evidence. Retired physicians do not suffer more psychiatric disorders than those who continue working. It is worth pointing that retirement is part of the decline of life, so no wonder the fear and rejection generated. Retirement can also be seen as a rite of passage or transition. Rites of passage are events that mark the most important transitions in human life, such as birth, initiation into adulthood, marriage and death. In the medical profession, the end of high school, obtaining professional qualifications and completion of a specialty, mark the different stages of the physician's career. Most research that has studied the quality of life of retired physicians agrees that most doctors are satisfied with their new condition. Similarly, retired doctors who said they were dissatisfied with their new situation, this was not because they had left the profession, but because they were in poor health or had no family or economic stability. The present study aims at providing an overview of occupational retirement from the individual and ontological point of view.


How important is the structure of school vaccine requirement opt-out provisions? Evidence from Washington, DC's HPV vaccine requirement.
Recent increases in vaccine-preventable diseases have led policymakers to reconsider the scope of vaccine requirement exemptions. Yet eliminating these provisions is politically difficult. Beginning in 2009, sixth grade girls in Washington, DC were required to receive the HPV vaccine or submit a one-time opt-out form. In 2014, the requirement was expanded to all students grades 6-12, and those not vaccinating were required to opt-out annually. I show that the movement from a one-time opt-out provision to an annual requirement increased the probability that teen girls in Washington, DC initiated HPV vaccination by 11 percentage points. Teen boys were 20 percentage points more likely to be vaccinated. Back-of-the-envelope calculations suggest 7 fewer cases of cervical cancer and 41 fewer cases of oropharyngeal cancer for the 33,000 enrolled during the 2017/2018 year. Using the initial value of cancer care and the value of a statistical life year, my estimates imply nearly $36 million in savings compared to $1.5 million spent on vaccination. In generalizing these results to other states, effect sizes even one-tenth the size of my most conservative estimate would imply meaningful reductions in the nationwide incidence of HPV-related cancers.


Improving Medical Q&A Matching by Augmenting Dual-Channel Attention with Global Similarity.
The emergence of online medical question-answer communities has helped to balance the supply of medical resources. However, the dramatic increase in the number of patients consulting online resources has resulted in a large number of repetitive medical questions, significantly reducing the efficiency of doctors in answering these questions. To improve the efficiency of online consultations, a large number of deep learning methods have been used for medical question-answer matching tasks. Medical question-answer matching involves identifying the best answer to a given question from a set of candidate answers. Previous studies have focused on representation-based and interaction-based question-answer pairs, with little attention paid to the effect of noise words on matching. Moreover, only local-level information was used for similarity modeling, ignoring the importance of global-level information. In this paper, we propose a dual-channel attention with global similarity (DCAG) framework to address the above issues in question-answer matching. The introduction of a self-attention mechanism assigns a different weight to each word in questions and answers, reducing the noise of "useless words" in sentences. After the text representations were obtained through the dual-channel attention model, a gating mechanism was introduced for global similarity modeling. The experimental results on the cMedQA v1.0 dataset show that our framework significantly outperformed existing state-of-the-art models, especially those using pretrained BERT models for word embedding, improving the top-1 accuracy to 75.6%.


An Unusual Flavin-Dependent Halogenase from the Metagenome of the Marine Sponge Theonella swinhoei WA.
Uncultured bacteria from sponges have been demonstrated to be responsible for the generation of many potent, bioactive natural products including halogenated metabolites.1 The identification of gene clusters from the metagenomes of such bacterial communities enables the discovery of enzymes that mediate new and useful chemistries and allows insight to be gained into the biogenesis of potentially pharmacologically important natural products. Here we report a new pathway to the keramamides (krm); the first functional evidence for the existence of a distinct producer in the Theonella swinhoei WA chemotype is revealed, and a key enzyme on the pathway, a unique flavin-dependent halogenase with a broad substrate specificity, with potential as a useful new biocatalytic tool, is described.


BMY-25801, an antiemetic agent free of D2-dopamine receptor antagonist properties.
BMY-25801, 4-amino-5-chloro-N-[2-(diethylamino)ethyl]2-(1-methyl-2-oxopropoxy ) benzamide, a new antiemetic agent free of D2-dopamine receptor antagonist properties, was effective against emesis induced by cytostatic agents (cisplatin, cyclophosphamide and doxorubicin) and total body radiation in the ferret. It also was effective against cisplatin-induced emesis in the dog; however, it was inactive against emesis caused by apomorphine and hydergine in the same species. In terms of activity profile, BMY-25801 could be differentiated both from metoclopramide and domperidone. Metoclopramide was nonselectively active against emesis induced by cytostatic agents, radiation and D2-dopamine receptor agonists, whereas domperidone was selectively effective against emesis induced by apomorphine and hydergine only. BMY-25801 failed to reveal any D2-dopamine receptor antagonist properties in several pharmacological tests (catalepsy, apomorphine stereotypy, serum prolactin, striatal dihydroxyphenylacetic acid and [3H]spiperone displacement) whereas metoclopramide was uniformly active in these tests. The activity profile of domperidone was compatible with its classification as a peripherally acting D2-dopamine receptor antagonist. BMY-25801 and metoclopramide antagonized serotonin-induced bradycardia (Bezold-Jarisch reflex) in the anesthetized rat, a response involving peripheral neuronal 5-HT3 receptors. Thus, BMY-25801 represents a novel antiemetic acting independently of D2-dopamine receptor mechanisms; however, its exact mode of action remains unknown.


Improving health in prisons - from evidence to policy to implementation - experiences from the UK.
Purpose The purpose of this paper is to understand the components of a high-quality prison healthcare system and the impact, ten-years on, of the transfer of accountability in England, from a justice ministry to a health ministry. Design/methodology/approach A rapid the evidence review was undertaken, which included a review of 82 papers and qualitative interviews with key informants. The concepts and themes identified were summarised and analysed through a framework analysis, designed to improve population outcomes and address health inequalities. The use of a rapid evidence assessment, rather than a systematic review methodology, the use of abstracts (rather than full-text articles) to extract the data, and limiting the search strategy to articles published in the English language only might mean that some relevant research papers and themes were not identified. The need for the evidence to be produced within a limited time frame and with limited resources determined these pragmatic approaches. Findings The review found that English prison healthcare has undergone "transformation" during this period, leading to increased quality of care through organisational engagement, professionalisation of the healthcare workforce, transparency, use of evidence-based guidance and responsiveness of services. The review also highlighted that there is still room for improvement, for example, relating to the prison regime and the lack of focus on early/preventive interventions, as well as specific challenges from limited resources. Research limitations/implications Time and resource constraints meant a rapid evidence review of papers in the English language was undertaken, rather than a systematic review. This might mean relevant papers have been missed. The review also only covered small number of countries, which may limit the transferability of findings. The lack of qualitative data necessitated the use of quantitative data gathered from key informants. However, this enabled a good understanding of current practice. Practical implications The review findings support the World Health Organisation position on the value of integrated prison and public health systems in improving quality of healthcare. It also recommends future policy needs to take account of the "whole prison approach" recognising that healthcare in prisons cannot operate in isolation from the prison regime or the community. Originality/value This is unique research which has great value in supporting prison reform in England. It will also be of interest internationally due to the paucity of data in the published peer-reviewed literature on the impact of commissioning models on healthcare or health outcomes.


[Dental materials and oral care products that can cause contact allergies].
Various restorative and prosthetic materials, dental implants, medicines and cosmetic materials, such as toothpaste and denture cleaning products, are used in oral care. In principle, these materials can cause contact allergies, which can manifest as lichenoid reaction, cheilitis and angioedema. It is usually a local reaction of the oral mucosa and surrounding tissues, but a systemic reaction can also occur elsewhere in the body. If a patient develops complaints from dental materials that could be due to an allergy, it makes sense to investigate this allergologically, although these do not yet show full specificity or sensitivity. After a positive allergological examination, it is possible to examine more specifically whether the patient's complaints match the test result and it can be decided whether it is sensible to replace the dental material and, if so, which material could be an alternative. After removal of the causative allergens, the complaints should disappear completely.


Investigation of pathways for the low-pH conformational transition in influenza hemagglutinin.
Targeted molecular dynamics simulations were used to study the conformational transition of influenza hemagglutinin (HA) from the native conformation to putative fusogenic or postfusion conformations populated at low pH. Three pathways for this conformational change were considered. Complete dissociation of the globular domains of HA was observed in one pathway, whereas smaller rearrangements were observed in the other two. The fusion peptides became exposed and moved toward the target membrane, although occasional movement toward the viral membrane was also observed. The effective energy profiles along the paths show multiple barriers. The final low-pH structures, which are consistent with available experimental data, are comparable in effective energy to native HA. As a control, the uncleaved precursor HA0 was also forced along the same pathway. In this case both the final energy and the energy barrier were much higher than in the cleaved protein. This study suggests that 1) as proposed, the native conformation is the global minimum energy conformation for the uncleaved precursor but a metastable state for cleaved HA; 2) the spring-loaded conformational change is energetically plausible in full-length HA; and 3) complete globular domain dissociation is not necessary for extension of the coiled coil and fusion peptide exposure, but the model with complete dissociation has lower energy.


Kondo-enhanced Andreev tunneling in InAs nanowire quantum dots.
We report measurements of the nonlinear conductance of InAs nanowire quantum dots coupled to superconducting leads. We observe a clear alternation between odd and even occupation of the dot, with subgap peaks at |V(sd)| = Delta/e markedly stronger (weaker) than the quasiparticle tunneling peaks at |V(sd)| = 2Delta/e for odd (even) occupation. We attribute the enhanced Delta peak to an interplay between Kondo correlations and Andreev tunneling in dots with an odd number of spins, and we substantiate this interpretation by a poor man's scaling analysis.


[Familial mitral valve prolapse and syncopes caused by ventricular tachycardia].
The authors report the case of a female aged 40 who was subject to syncopal attacks, and had an apical end-systolic murmur. The presence of an idiopathic prolapse of the mitral valve was demonstrated, as well as the familial nature of the condition, and the fact that the syncopal attacks were caused by ventricular tachycardia, The case report is followed by a discussion of the cardiac arrhythmias which are likely to accompany this particular mitral lesion, the difficulties in treatment which arise, and finally the danger of sudden death by ventricular fibrillation inherent in this condition, a danger which it is stille difficult to quantify.


Application of cytogenetic methods to analysis of etiologic factors in carcinogenesis.
The study of chromosomal aberrations in tumour cells by means of modern banding techniques has become a rapidly expanding branch of cancer research. Large amounts of information about cancer-associated chromosomal aberrations have accumulated, and new data continue to appear at a rapid rate. The systematic evaluation of these data has disclosed a number of correlations between chromosomal change and neoplastic disease in experimental animals and man: (1) Chromosomal aberrations are strictly non-random, and in several instances the aberrations are highly consistent and show a remarkable degree of specificity. (2) Chromosomes selectively involved in different types of neoplasia cluster to certain specific chromosome types, and evidence has been presented indicating that certain chromosomal regions may be affected selectively. (3) Suggestive results from work with experimental tumours indicate a direct interaction between the tumour-inducing factor and the chromosomes of the host cell. A hypothetical model, originally proposed by Levan and Mitelman (1977) and elaborated in detail by Mitelman and Levan (1981) to explain the role of chromosomal aberrations in malignant development, is presented. According to this idea, the chromosomal aberrations associated with malignancy may be of essentially two distinct kinds, with different modes of origin. One kind of aberration, the primary or active, arises from direct interaction between the inducing agent and the genetic material of the target cell. Primary aberrations are therefore located in specific chromosomal regions. The other kind of aberration, the secondary or passive, arises by chance disturbances of mitosis. Since, however, only those secondary changes that happen to enhance the effect of the primary change have selective value and will thus accumulate in a population, the passive changes exhibit distinct nonrandom patterns that reflect the primary changes. Conversely, it should be possible to deduce from the distribution of aberrations which chromosomes were originally affected by a primary change; and close observation of those chromosomes involved in nonrandom changes should therefore give indications as to the location in the genome of the original lesions induced by the oncogenic agent.


Evaluating clinical placements in Saudi Arabia with the CLES+T scale.
The clinical learning environment and supervision (CLES) tool has been enhanced with an additional sub-scale for measuring the quality of nurse teacher's involvement to form the CLES + T scale. It has been widely used in many countries to evaluate clinical placements. Here we report data from Saudi Arabia. The CLES + T was employed to measure satisfaction among student nurses concerning their clinical learning environment. Linear regression was used to determine relationships of various variables to the outcomes of total CLES + T score and those of its subscales. Students were generally satisfied with their placements. For female students the number of visits of the nurse tutor was positively associated with most subscales and with the total score. For males, who had fewer visits from a nurse tutor, there was no such association. Nurse tutor visits are positive in terms of clinical placement evaluation by female student nurses. Saudi nursing students are generally similar to students in other international studies in terms of their appraisal of clinical placements.


Sex ratio of sea turtles: seasonal changes.
Sex ratios of hatchling loggerhead turtles Caretta caretta taken from South Carolina and Georgia ranged from no females in nests laid in late May to 80 percent females in those laid in early July; the sex ratio decreased to 10 percent females in nests laid in early August. These seasonal changes are consistent with the role of temperature in directing sexual differentiation in various reptiles. The data have implications for understanding the demography of sea turtles and for their conservation.


Is prosthetic renal artery reconstruction a durable procedure? An analysis of 489 bypass grafts.
Renal artery stenosis has been classically addressed with saphenous vein bypass graft or transaortic endarterectomy performed either primarily or in combination with an aortic procedure. In this series, we report the outcome of our 12-year experience with renal artery reconstruction using prosthetic conduit. Patients undergoing renal artery bypass grafting from 1987 to 1999 were identified. Demographics, indications, concurrent operations, complications, and patency were analyzed. Patients underwent postoperative duplex scan with subsequent ultrasound scans at 6-month intervals. There were 489 procedures performed in 414 patients with indications: high-grade renal artery stenosis in combination with abdominal aortic aneurysm repair or symptomatic aortoiliac occlusive disease (309 [63%]), renovascular hypertension (118 [24%]), and renal salvage (20 [4%]). Indications for the remainder included trauma, renal artery aneurysm, or an infected aortic graft. Inflow was aorta or aortic graft in 95% of patients with the remainder taken from the iliac or visceral vessels. The retroperitoneal approach was used in 97.8%. Nonfatal complications occurred in 11.4% with a 1.4% early and 4.8% late occlusion rate. Renal function worsened in 3.1% of all patients. Secondary patency at 1 and 5 years was 98% and 96%, respectively. Renal artery reconstruction with prosthetic conduit has an acceptable and durable result whether used for primary renal artery reconstruction or concomitant reconstruction with aortic procedures.


Mechanism of Chloramphenicol Resistance in Staphylococcus epidermidis.
The mechanism of chloramphenicol resistance in several multiple-resistant Staphylococcus epidermidis strains has been studied and shown to be due to the presence of the enzyme, chloramphenicol acetyltransferase. As with S. aureus, the inactivating enzyme in S. epidermidis appears to be the product of a structural gene on the chloramphenicol plasmid because resistance and enzyme activity are concurcurrently lost after growth in acridine orange or at elevated temperatures. The synthesis of chloramphenicol acetyltransferase in S. epidermidis has been compared with the function of a similar enzyme in chloramphenicol-resistant S. aureus with the conclusion that the kinetics of induction, products of the reaction, and general properties of the enzymes are identical. The chloramphenicol acetylating enzyme from S. epidermidis has been purified to a state of homogeneity and compared with the analogous purified S. aureus enzyme. Both purified preparations consist of native enzymes with molecular weights of 80,000, and evidence is presented that is consistent with their being made up of four identical subunits of 20,000 each. The two staphylococcal enzymes are identical with respect to pH optimum, apparent affinity (K(m)) for chloramphenicol, heat denaturation, and immunological reactivity, but they differ in electrophoretic mobility, chromatographic behavior, substrate specificity, and sensitivity to inhibition by mercuric ion.


Acute Kidney Injury Predictors and Outcomes after Cardiac Surgery in Children with Congenital Heart Disease: An Observational Cohort Study.
Acute Kidney Injury (AKI) commonly complicates cardiac surgery in children with congenital heart disease (CHD). In this study we assessed incidence, risk factors, and outcomes of postoperative AKI, while testing the hypothesis that, depending on the underlying diagnosis, there would be significant differences in AKI incidence among different diagnostic groups. We conducted an observational cohort study of children with CHD undergoing cardiac surgery in a single tertiary center between January 2019 and August 2021 (n = 362). Kidney Disease Improving Global Outcome (KDIGO) criteria were used to determine the incidence of postoperative AKI. Diagnosis was incorporated into multivariate models using an anatomic-based CHD classification system. Overall survival was estimated using Kaplan−Meier curves. Log-rank test and adjusted Cox proportional hazard modelling were used to test for differences in survival distributions and determine AKI effect on survival function, respectively. AKI occurred in 70 (19.3%), with 21.4% in-hospital mortality for AKI group. Younger age, lower weight, longer cardiopulmonary bypass time, preoperative mechanical ventilation and diagnostic category were associated with postoperative AKI. Resolution rate was 92.7% prior to hospital discharge for survivors. AKI was associated with longer duration of mechanical ventilation, ICU and hospital length of stay. AKI patients had significantly higher probability of all-cause mortality postoperatively when compared to the non-AKI group (log-rank test, p < 0.001). Adjusted hazard ratio for AKI versus non-AKI group was 11.08 (95% CI 2.45−50.01; p = 0.002). Diagnostic category was associated with cardiac surgery-related AKI in children with CHD, a finding supporting the development of lesion specific models for risk stratification. Postoperative AKI had detrimental impact on clinical outcomes and was associated with decreased survival to hospital discharge.


Does the world leak into the mind? Active externalism, "internalism" and epistemology.
One of the arguments for active externalism (also known as the extended mind thesis) is that if a process counts as cognitive when it is performed in the head, it should also count as cognitive when it is performed in the world. Consequently, mind extends into the world. I argue for a corollary: We sometimes perform actions in our heads that we usually perform in the world, so that the world leaks into the mind. I call this internalism. Internalism has epistemological implications: If a process gives us an empirical discovery when it is performed in the world, it will also give us an empirical discovery when it is performed in the head. I look at a simple example that highlights this implication. I then explore the relation between internalism and active externalism in more detail and conclude by comparing internalism with mental modeling.


[Preoperative Detection of Pleural Adhesions Using Transthoracic Ultrasonography].
Recently, there has been an increase in the experience of lung surgery in cases with a history of thoracotomy or pneumonia. In these cases, pleural adhesion is often seen and makes the surgery to be difficult. Especially in thoracoscopic surgery, lung damage must be care at the 1st port insertion. In this report, the usefulness of the extent of pleural adhesion to the chest wall before surgery by using a transthoracic ultrasonography was assessed. Between April 2017 and September 2018, 32 patients underwent preoperative ultrasound examination, and 128 ports were evaluated whether had adhesions or not using lung sliding sign. All patients of 128, 24 adhesions were found at surgery, resulting in 14 true positive, 10 false negative, 0 false positive, and 104 true negative findings [sensitivity:58.3% (14/24), specificity: 100.0% (104/104), accuracy:92.2% (118/128)]. Especially, about the 1st port, accuracy was 93.8 % (30/32). In Conclusion, preoperative transthoracic ultrasonography could provide useful information on the pleural adhesion leading safe initial thoracoscopic access without lung injury.


Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology.
Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling. Here, we combine human iPSCs and airway-on-a-chip technology, to demonstrate the effectiveness of fluid shear stress (FSS) for regulating the global axis of multicellular planar cell polarity (PCP), as well as inducing ciliogenesis, thereby contributing to quantifiable unidirectional mucociliary flow. Furthermore, we applied the findings to disease modeling of primary ciliary dyskinesia (PCD), a genetic disease characterized by impaired mucociliary clearance. The application of an airway cell sheet derived from patient-derived iPSCs and their gene-edited counterparts, as well as genetic knockout iPSCs of PCD causative genes, made it possible to recapitulate the abnormal ciliary functions in organized PCP using the airway-on-a-chip. These findings suggest that the disease model of PCD developed here is a potential platform for making diagnoses and identifying therapeutic targets and that airway reconstruction therapy using mechanical stress to regulate PCP might have therapeutic value.


Atypical onset of total colonic Hirschsprung disease in a small female infant: A case report.
Hirschsprung disease (HD) or colonic aganglionosis is a congenital disorder, which results from the abnormal migration of neuronal cells of the neural crest leading to a disorder of the enteric nervous system consisting in the absence of ganglion cells within the submucosal and myenteric plexus. We report the case of a 7-month-old female infant admitted in our clinic for constipation and failure to thrive. At the age of 6 months, she was examined in our clinic for the same reasons, and we recommended symptomatic treatment without improvements. The clinical examination revealed pallor of the skin and mucosa, distended abdomen, and abdominal tenderness at palpation. The abdominal ultrasound showed abdominal bloating, and the barium enema was normal. The patient's evolution worsened progressively within the following 3 days after admission associating sings of toxic megacolon. She underwent a surgical intervention with total colectomy and ileostomy, and the final diagnosis confirmed by the histological examination was of total colonic aganglionosis (TCA). The evolution immediately after the surgery and the follow-up examination after approximately 3 months pointed out normal weight gain and the laboratory tests were within normal limits. TCA can also manifest in older infants. Barium enemas can guide the diagnosis in most cases of HD. Nevertheless, in patients with TCA, it can be normal. Moreover, it could represent a trigger for toxic megacolon.


Comorbidity of Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Disease Exert Significant Effect on RBC Indices.
Glucose-6-phosphate dehydrogenase (G6PD) converts glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway and protects red blood cells (RBCs) from oxidative damage. Their deficiency therefore makes RBCs prone to haemolysis. Sickle cell disease (SCD) on the other hand is a hereditary blood disorder in which there is a single nucleotide substitution in the codon for amino acid 6 substituting glutamic acid with valine. SCD patients are prone to haemolysis due to the shape of their red blood cells and if they are deficient in G6PD, the haemolysis may escalate. Reported studies have indicated variations in the prevalence of G6PD deficiency in SCD patients and as such further work is required. The aim of this study was therefore to estimate the incidence of G-6-PD deficiency among SCD patients and to determine its impact on their RBC parameters as a measure of incidence of anaemia. A total of 120 clinically diagnosed SCD patients of genotypes HbSS and HbSC were recruited into the study. About 5ml of blood was collected via venipuncture from each patient and used to run G6PD, full blood count, and haemoglobin (Hb) electrophoresis tests. The data were analyzed using SPSS version 20 and Graphpad prism. G6PD deficiency was detected in 43 (35.83%) of the participants made up of 16 (13.33%) males and 27 (22.50%) females of whom 17 (14.17%) had partial deficiency and 10 (8.33%) full deficiency. Statiscally significant differences p=0.036 and p=0.038 were established between the Hb concentration of the participants having a G6PD deficiency and those with normal G6PD activity for males and females, respectively. From the results obtained, it implies that G6PD deficiency may increase the severity of anaemia in SCD patients. There is therefore the need to screen all SCD patients for G6PD deficiency to ensure that their condition is not exacerbated during treatment.


Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study.
The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.


A fast nonparametric noncausal MRF-based texture synthesis scheme using a novel FKDE algorithm.
In this paper, a new algorithm is proposed for fast kernel density estimation (FKDE), based on principal direction divisive partitioning (PDDP) of the data space. A new framework is also developed to apply FKDE algorithms (both proposed and existing), within nonparametric noncausal Markov random field (NNMRF) based texture synthesis algorithm. The goal of the proposed FKDE algorithm is to use the finite support property of kernels for fast estimation of density. It has been shown that hyperplane boundaries for partitioning the data space and principal component vectors of the data space are two requirements for efficient FKDE. The proposed algorithm is compared with the earlier algorithms, with a number of high-dimensional data sets. The error and time complexity analysis, proves the efficiency of the proposed FKDE algorithm compared to the earlier algorithms. Due to the local simulated annealing, direct incorporation of the FKDE algorithms within the NNMRF-based texture synthesis algorithm, is not possible. This work proposes a new methodology to incorporate the effect of local simulated annealing within the FKDE framework. Afterward, the developed texture synthesis algorithms have been tested with a number of different natural textures, taken from a standard database. The comparison in terms of visual similarity and time complexity, between the proposed FKDE based texture synthesis algorithm with the earlier algorithms, show the efficiency.


Expression of osteoprotegerin in placenta and its association with preeclampsia.
Osteoprotegerin (OPG), a key regulatory factor in bone metabolism, was documented also a potential pro-angiogenic factor, which acts an important role in protecting vascular endothelial cells. Since preeclampsia has gradually been employed to be vascular diseases, we speculated that OPG might be associated with preeclampsia. The study was to evaluate the level of OPG protein and mRNA in placenta, and investigate the relationship between OPG and the pathogenesis of preeclampsia. Placental specimens from 30 term normal pregnancy, 30 severe preeclampsia and 30 mild cases were studied. The expression and levels of OPGs' protein and mRNA were detected by immunohistochemistry, western blot analysis and real-time quantitative PCR analysis respectively. The expression of OPG protein was found in cytoplasm of placenta cytotrophoblasts and syncytiotrophoblasts in three groups. There were no significant differences of OPG protein between the maternal and fetal side in each group. The OPG protein and mRNA levels in severe preeclampsia were significantly higher than those in mild cases and normal pregnancy. However, there were no markedly differences of the OPG protein and mRNA levels between term delivery and preterm delivery in severe cases. In preeclampsia, the OPG protein and mRNA level was positively correlated with systolic blood pressure and 24 h urinary protein respectively. OPG protein and mRNA level in placentas of preeclampsia were found abnormal compared with normal pregnancy. In preeclampsia, the OPG protein and mRNA levels were closely related with its important clinical parameters. Taken together, OPG might be closely correlated with the pathogenesis of preeclampsia.


Dynamically generated hierarchies in games of competition.
Spatial many-species predator-prey systems have been shown to yield very rich space-time patterns. This observation begs the question whether there exist universal mechanisms for generating this type of emerging complex patterns in nonequilibrium systems. In this work we investigate the possibility of dynamically generated hierarchies in predator-prey systems. We analyze a nine-species model with competing interactions and show that the studied situation results in the spontaneous formation of spirals within spirals. The parameter dependence of these intriguing nested spirals is elucidated. This is achieved through the numerical investigation of various quantities (correlation lengths, densities of empty sites, Fourier analysis of species densities, interface fluctuations) that allows us to gain a rather complete understanding of the spatial arrangements and the temporal evolution of the system. A possible generalization of the interaction scheme yielding dynamically generated hierarchies is discussed. As cyclic interactions occur spontaneously in systems with competing strategies, the mechanism discussed in this work should contribute to our understanding of various social and biological systems.


CRYPTOSPORIDIOSIS AND ITS GENOTYPES AMONG CHILDREN ATTENDING MOI TEACHING AND REFERRAL HOSPITAL IN ELDORET, KENYA.
To determine the prevalence of cryptosporidiosis and the associated factors, and characterise the Cryptosporidium isolates from children aged five years and less with diarrhoea. A prospective cross-sectional study. This was a health facility and laboratory based study. Screening for Cryptosporidium oocysts was done at the Microbiology laboratory, School of Medicine, Moi University, Eldoret and genotyping and sub-genotyping at the Kenya Medical Research Institute, Nairobi, Kenya. Children aged five years and less seen at the outpatient clinic and those admitted in the pediatric wards at MTRH were recruited into the study upon obtaining assent and written consent from the parents or guardians. The prevalence of cryptosporidiosis was 9.8% (N = 317). A duration of diarrhoea of more than two weeks was associated with cryptosporidiosis (OR = 1.8301) compared to those with diarrhoea for less than one week. There were no sex related differences in the cryptosporidiosis prevalence (P = 0.9752). Waste disposal, water sources and treatment, and livestock in homesteads were not associated with cryptosporidiosis. About 82% of the isolates were C. hominis and 18% were C. parvum. There were 6 subtypes of C. hominis and 4 subtypes of C. parvum in circulation. The prevalence of cryptosporidiosis is comparable to other regions of the worldwith C. hominis being the most common followed by C. parvum. Human-to-human transmission is the mainmode of spread of cryptosporidiosis. All the Cryptosporidium isolates were from children residing in peri-urban and rural areas.


[Surgical treatment for metachronous lung cancer].
We performed a retrospective review of 45 consecutive patients with metachronous multiple primary lung cancer who underwent resection between 1990 and 2009. Surgical treatment of the 1st tumor consisted of 39 lobectomies and 3 segmentectomies, and 3 wedge resections. The 2nd tumor was removed by means of a lobectomy in 9 patients, a segmentectomy in 17 patients, a wedge resection in 19 patients. No postoperative mortality was observed. Histologic classification was similar in 86.4% of patients and different in 13.6%. Postoperative stage of the 2nd tumor was IA in 31 patients, IB in 7, IIA in 1, IIIA in 3, IIIB in 3. Median follow-up was 48.4 months after 2nd operation. The 5-year survival rate was 90.8% after 1st operation and 85.6% after 2nd operation. The 5-year survival rate in patients with p-stage IA was 96.4%. Patients with metachronous lung cancer could have a favorable outcome. Thus we need careful follow-up of the patients after treatment on the 1st lung cancer, and moreover an aggressive surgical treatment is recommended as long as their performance state or residual pulmonary function allows.


Synthesis and determination of 10-oxomorphine, a decomposition product of morphine.
10-Oxomorphine, a decomposition product of morphine, was synthesized from 6-O-acetylcodeine, which was oxidized with chromic acid to 6-O-acetyl-10-hydroxycodeine. This substance was then oxidized with manganese dioxide to 6-O-acetyl-10-oxocodeine, which on hydrolysis and O-demethylation gave 10-oxomorphine. UV-, fluorimetric spectrometry, TLC and HPLC methods were used for determination of 10-oxomorphine.


Femoral anteversion and arthritis of the knee.
Anteversion and arthritic changes were recorded in 110 well-preserved femora to identify a correlation between knee osteoarthritis and anteversion. Arthritis was recorded as no change (grade 0), osteophytes (grade 1), cysts or erosions (grade 2), and burnishing or eburnation (grade 3). Anteversion was identified by measure of the angle between the axis of the head-neck and the axis of the posterior condyles. There was no relation between anteversion and proximal femoral arthritis but increased arthritis of the distal femur with decreased anteversion (p < 0.04) was identified, establishing a correlation between femoral anteversion and arthritis of the knee.


Cell adhesion molecules in oesophageal epithelium.
The distribution of a range of integrins, E-cadherin, and carcino-embryonic antigen (CEA) like molecules in normal human oesophageal epithelium was investigated immunohistochemically on frozen sections of endoscopic biopsy specimens. The integrin subunits alpha 2, alpha 3, alpha 6, alpha v, beta 1, and beta 5 were expressed throughout the epithelium. There was strong expression of alpha 2, alpha 3, and beta 1 subunits in the basal cell layer and for all the subunits studied the intensity of the staining decreased as cells moved towards the lumen. The heterodimer alpha v beta 3 was expressed weakly in the basal aspect of the basal cell layer only. The CEA molecules were not present in the basal cells layer but there was weak expression in the prickle cell layer and strong positivity in the mature functional layer. E-cadherin was found throughout the epithelium but was weakly expressed at the basal aspect of the basal cells layer and showed strong positivity in the prickle cell and squamous cell layers. These results indicate that cell-cell (E-cadherin, CEA) and cell-matrix (integrins) adhesion molecules show a well defined spatial pattern of immunoreactivity in the oesophageal mucosa and may play a part in the maintenance of normal tissue architecture and physiological homeostasis.


Congenital curved nail of the fourth toe.
Five cases of congenital curved nail of the fourth toe are reported. Patients included four males and one female; four cases were bilateral, and one was unilateral. There were no other significant associated anomalies of the extremities, and only the fourth toes were affected. The features of the deformity are a curved nail and hypoplasia of the soft tissue and bone of the distal phalanx of the fourth toe. This anomaly may be transmitted autosomally and is unique in that it may be of mesodermic origin.


Differences in liver fibrosis and response to pegylated interferon plus ribavirin in HIV/HCV-coinfected patients with normal vs elevated liver enzymes.
Severity of liver fibrosis and response to pegylated interferon plus ribavirin (pegIFN-RBV) are not well known in HIV/HCV-coinfected patients with persistently normal alanine aminotransferase (PNALT). All HIV/HCV-coinfected patients who had been assessed for liver fibrosis using elastometry during 2005 at our clinic were evaluated. Those with at least 1 year with three prior consecutive ALT measurements below the upper limit of normality were compared with patients with elevated ALT. Response to pegIFN-RBV was assessed in a subset of these patients. We analysed 87 patients with PNALT and 122 with elevated ALT. Compared to patients with elevated ALT, those with PNALT were significantly more often women (42%vs 26%), had greater mean CD4 counts (565 vs 420 cells/mm³), had lower mean serum HCV-RNA (5.8 vs 6.2 log IU/ml) and were infected by HCV genotype 4 (33%vs 6%). Liver fibrosis was considered as severe (Metavir F3) in 10% of patients with PNALT, and another 4% had cirrhosis based on stiffness values. These numbers were 16% and 35% in patients with elevated ALT. Treatment with pegIFN-RBV was given to 22 and 45 patients with PNALT and elevated ALT, respectively. Sustained virological response was achieved in 50% and 29% of them. In the multivariate analysis, PNALT was independently associated with response (OR: 7.9; 95% CI: 1.4-45.2; P = 0.02). Nearly 15% of HIV/HCV-coinfected patients with PNALT showed advanced liver fibrosis (Metavir F3-F4 estimates by elastometry). In summary, response to pegIFN-RBV is higher in patients with PNALT than in those with elevated ALT. Therefore, treatment should not be denied in HIV/HCV-coinfected patients with PNALT.


Correlation between the acetabular diameter and thickness in Thais.
We conducted a study on dried cadaveric pelvic bones to determine the relation between acetabular diameter and thickness of the acetabular wall. The acetabulum was divided into four quadrants: antero-superior, postero-superior, postero-inferior, and antero-inferior. The diameters of the acetabulum were measured for 152 pelvic bones. The thickness of the center of the acetabulum was measured with the use of a caliper at four quadrants of the acetabulum. The average acetabular diameter was found to be 51.8224 mm for all the acetabuli. The average thickness in the posterior quadrant has been calculated to be about 50% of the acetabular diameter, which is about 26 mm. The acetabular diameter and the thickness of the acetabulum correlated very well though there was very little significance statistically (0.099) due to the lack of full data for all the individual bones. Linear correlation between the thickness and the diameter is definitely collinear but the correlation is not statistically significant. Some additional factors such as bone density, body mass, etc, are required to correlate the thickness and the diameter. Further study is required in this field.


Relationship between Perme ICU Mobility Score and length of stay in patients after cardiac surgery.
Patients undergoing cardiac surgery can experience functional impairment. Assess the influence of Perme Score on the intensive care unit (ICU) length of stay in patients after cardiac surgery. As a secondary objective, investigate if preoperative variables can predict the patient's mobility status after surgery. A prospective observational study was conducted in ICU in a university hospital. The mobility status (Perme Score) was collected from the first postoperative day until ICU discharge. The preoperative assessment of respiratory muscle strength, pulmonary function, and handgrip strength were collected. A total of 44 patients, mean age of 62.3 years, 28 men were included in the study. A high Perme Score on the second postoperative day among patients who underwent Coronary artery bypass grafting and the third postoperative day on three types of intervention (Coronary artery bypass grafting, valve replacement, or both simultaneously) was associated with shorter ICU length of stay). The preoperative pulmonary function was one of the main independent predictors of mobility status on the first three days of ICU stay, in addition to left ventricular ejection fraction and cardiopulmonary bypass time on the first day, age, and left ventricular ejection fraction on the second day and maximum expiratory pressure on third day. An increase in mobility status (Perme Score), mainly on the third postoperative day, reduced the ICU stay, mainly influenced by preoperative pulmonary function.


A negative myocardial perfusion scintigram after coronary angioplasty confers benign long-term prognosis.
Myocardial perfusion SPECT is often used to exclude late restenosis or disease progression after coronary angioplasty (PTCA), but few studies have been published regarding the prognostic value of a negative study. To examine the long-term prognostic value of a non-ischemic SPECT result after successful PTCA. We retrospectively reviewed 783 patients (pts) who underwent scintigraphy 3 months to 3 years after successful PTCA. In 118 no significant myocardial ischemia (moderate or severe) was observed. There was a history of myocardial infarction (MI) in 38.1%, multivessel disease in 36.8% and LVEF < 50% in 15.3%. Referral for SPECT was chronic angina in 50.5% and acute coronary syndrome in 32.2%. SPECT was performed using a treadmill exercise test in 72%, adenosine in 21%, dipyridamole in 3% and dobutamine in 4%. Fifty-three percent of pts were under anti-ischemic medication. Patients were divided into two groups according to the SPECT result: group A pts (n = 70) had mild or no ischemia and group B pts (n = 48) had non-reversible defects of small or moderate size. The endpoint was the combined occurrence of death, MI, unstable angina (UA) and repeated revascularization. There were one MI, 2 UA episodes and 4 repeated PTCAs (1 for UA). Event-free survival rate at two-year follow-up was slightly lower in patients from group B compared with group A, respectively 91.7% versus 97.1% (p = 0.16, log rank test). This study suggests an excellent prognosis for patients with no or mild ischemia as assessed by SPECT performed more than 3 months after coronary angioplasty. Those patients with mild persistent defects did not present a significantly worse outcome.


Decrement in bone mineral density after parathyroidectomy in a pediatric patient with primary hyperparathyroidism.
Primary hyperparathyroidism (PHT) causes increased bone turnover, leading to reduction in bone mineral density (BMD). Parathyroidectomy is a definitive therapy and improves BMD in adult patients with PHT. However, there are no reports regarding alterations of BMD in pediatric or adolescent patients with PHT. Here, we report a case of a 13-yr-old boy with PHT who was referred to our institution for evaluation of hypercalcemia and hyperparathyroidism. Radiological investigation revealed an ectopic parathyroid adenoma below the right thyroid lobe. A minimally invasive radio-guided parathyroidectomy was successfully performed. We followed up the patient's BMD for three years both before and after parathyroidectomy. Over the course of three years, his BMD was steadily decreased, with z-scores of +0.506 at 13 yr and 9 mo, +0.162 at 14 yr and 9 mo, and -0.411 at 15 yr and 9 mo. BMD usually increases during peak height velocity in an adolescent and improves after parathyroidectomy in adult patients with PHT. However, our patient showed decreased BMD z-scores following parathyroidectomy. Therefore, the patient had an increased risk of fracture after parathyroidectomy and was followed up closely. Both height and BMD should be carefully evaluated after parathyroidectomy in pediatric and adolescent patients with PHT.


Breakup of pangaea and isolation of relict mammals in australia, South america, and madagascar.
The composition of aboriginal land mammal faunas in Australia and New Guinea (prototherians and metatherians), South America (metatherians and eutherians) and Madagascar (eutherians only) is reconsidered in light of continental drift reconstructions of Mesozoic-Tertiary world paleogeography It is proposed that these three faunas represent successively detached samples of the evolving world mammal fauna as it existed when each of these land masses became faunally isolated from the rest of the world as a result of the progressive fragmentation of Pangaea. Isolation of aboriginal prototherians and metatherians in Australia and New Guinea may date from the Upper JurassicLower Cretaceous; isolation of aboriginal metatherians and eutherians in South America may date from the Middle Cretaceous-Upper Cretaceous; isolation of aboriginal eutherians in Madagascar may date from the Paleocene-Eocene.


Evaluation of Suspected Small Bowel Ischemia Using Contrast-Enhanced Ultrasound with Computed Tomography Fusion.
Small bowel ischemia can lead to fatal complications such as necrosis, perforation, and sepsis. Clinical examinations and laboratory tests are usually inconclusive in critically ill patients. The need for surgical exploration is decided based on imaging, examination, and clinical judgment. The decision to operate is time-critical and can be lifesaving, but surgical intervention has the potential to cause additional morbidity, especially in unstable patients. Contrast-enhanced computed tomography (CECT) is the study of choice in suspected small bowel ischemia but has poor specificity. Contrast-enhanced ultrasound (CEUS) provides real-time visualization of the bowel wall vascularity. In this case report, we used a CEUS with CT fusion examination to rule out small bowel ischemia in a critically ill patient with suspected closed loop small bowel obstruction on CECT and in whom surgical exploration would have not been well tolerated. The patient's condition later improved, and an abdominal CT showed no evidence of obstruction.


Measurement of the Electrically Evoked Stapedial Reflex Response with Wideband Acoustic Reflectance Measurement.
The electrically evoked stapedial reflex threshold (ESRT) has been shown to be a good predictor of upper stimulation level for cochlear implant recipients. Previous research has shown that the ESRT may be recorded at lower stimulation levels and with a higher incidence of success with the use of higher frequency probe tones (e.g., 678 and 1000 Hz) relative to the use of the conventional 226-Hz probe tone. Research has also shown that the acoustic reflex may be recorded at lower stimulus levels with the use of wideband reflectance when compared to the acoustic reflex threshold recorded with a conventional acoustic immittance measurement. The objective of this study was to compare the ESRT recorded with acoustic immittance and wideband reflectance measurements. A repeated measures design was used to evaluate potential differences in ESRTs with stimulation at an apical, middle, and basal electrode contact with the use of two different techniques, acoustic immittance measurement and wideband reflectance. Twelve users of Cochlear Nucleus cochlear implants were included in the study. Participants' ESRTs were evaluated in response to simulation at three different electrode contact sites (i.e., an apical, middle, and basal electrode contact) with the use of two different middle ear measurement techniques, acoustic immittance with the use of a 226-Hz probe tone and wideband reflectance with the use of a chirp stimulus. The mean ESRT recorded with wideband reflectance measurement was significantly lower when compared to the ESRT recorded with acoustic immittance. For one participant, the ESRT was not recorded with acoustic immittance before reaching the participant's loudness discomfort threshold, but it was successfully recorded with the use of wideband reflectance. The ESRT may potentially be recorded at lower presentation levels with the use of wideband reflectance measures relative to the use of acoustic immittance with a 226-Hz probe tone. This may allow for the ESRT to be obtained at levels that are more comfortable for the cochlear implant recipient, which may also allow for a higher incidence in the successful recording of the ESRT.


Evaluation of the ICT malaria P.f/P.v and the OptiMal rapid diagnostic tests for malaria in febrile returned travellers.
Rapid diagnostic tests (RDTs) are less reliant on expert microscopy and have the potential to reduce errors in malaria diagnosis but have not been extensively evaluated in nonimmune persons or in countries where infection is not endemic. We evaluated the ICT P.f/P.v (ICT-Amrad, Sydney, Australia) and OptiMal (Flow Inc., Portland, Oreg.) assays prospectively for the diagnosis of malaria in 158 specimens from 144 febrile returned travellers in Australia by using expert microscopy and PCR as reference standards. Malaria was diagnosed in 93 specimens from 87 patients by expert microscopy, with 3 additional specimens from recently treated patients testing positive for Plasmodium falciparum by PCR. For the diagnosis of asexual-stage P. falciparum malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 97 and 90%, respectively, and those of the OptiMal assay were 85 and 96%, respectively. The ICT P.f/P.v assay missed one infection with a density of 45 parasites/ micro l, whereas the OptiMal assay missed infections up to 2,500/ micro l; below 1,000/ micro l, its sensitivity was only 43%. For the diagnosis of P. vivax malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 44 and 100%, respectively, and those of the OptiMal assay were 80 and 97%, respectively. Both assays missed infections with parasite densities over 5,000/ micro l: up to 10,000/ micro l with the former and 5,300/ micro l with the latter. Despite the high sensitivity of the ICT P.f/P.v assay for P. falciparum malaria, caution is warranted before RDTs are widely adopted for the diagnosis of malaria in nonimmune patients or in countries where malaria is not endemic.


Noise mode response at peak exercise in a DDD pacemaker.
The noise sampling period has been recognized as a cause of apparent sensing malfunction in demand pacemakers. Physiologic signals as well as external electromagnetic interference can cause certain demand pacemakers to remain refractory and escape asynchronously at a specified rate. In this case, noise mode reversion pacing at the programmed lower rate limit of a Cordis 415A DDD pacemaker was observed during exercise when P-waves fell within the noise sampling period.


Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma.
Oral cancer is the sixth most common cause of death from cancer with an estimated 400,000 deaths worldwide and a low (50%) 5-year survival rate. The most common form of oral cancer is oral squamous cell carcinoma (OSCC). OSCC is highly inflammatory and invasive, and the degree of inflammation correlates with tumor aggressiveness. The G protein-coupled receptor protease-activated receptor-2 (PAR-2) plays a key role in inflammation. PAR-2 is activated via proteolytic cleavage by trypsin-like serine proteases, including kallikrein-5 (KLK5), or by treatment with activating peptides. PAR-2 activation induces G protein-α-mediated signaling, mobilizing intracellular calcium and Nf-κB signaling, leading to the increased expression of pro-inflammatory mRNAs. Little is known, however, about PAR-2 regulation of inflammation-related microRNAs. Here, we assess PAR-2 expression and function in OSCC cell lines and tissues. Stimulation of PAR-2 activates Nf-κB signaling, resulting in RelA nuclear translocation and enhanced expression of pro-inflammatory mRNAs. Concomitantly, suppression of the anti-inflammatory tumor suppressor microRNAs let-7d, miR-23b, and miR-200c was observed following PAR-2 stimulation. Analysis of orthotopic oral tumors generated by cells with reduced KLK5 expression showed smaller, less aggressive lesions with reduced inflammatory infiltrate relative to tumors generated by KLK5-expressing control cells. Together, these data support a model wherein KLK5-mediated PAR-2 activation regulates the expression of inflammation-associated mRNAs and microRNAs, thereby modulating progression of oral tumors.


Extension of liver tissue into the thorax following a right extrapleural pneumonectomy for malignant pleural mesothelioma.
A 56-year-old male underwent a right extrapleural pneumonectomy for malignant pleural mesothelioma. Two years after the operation, an intrathoracic mass was suspected of recurrence by imaging, however, biopsy revealed that the mass was actively proliferating liver tissues. We discussed this condition in terms of ectopic liver proliferation.


Field dependence/independence and performance in school: an argument against neutrality of cognitive style.
To ascertain whether there is any relationship between field dependence/independence and performance in school, the Children's Embedded Figures Test and Embedded Figures Test were applied to 103 10- to 14-yr.-olds (55 boys and 48 girls) in Grades 5 to 8 of primary education and Grade 1 of secondary education in Santiago de Compostela (Spain), and the scores were compared with their school marks in Mathematics, Spanish, Natural Sciences, and Social Sciences, and with their over-all mark. Field-independent children performed better in all subjects, especially boys. This finding appears unsupportive of the supposed neutrality of field dependence/independence and suggests that this dimension of cognitive style should be taken into account in education.


Correlation of mean platelet volume, neutrophil-to-lymphocyte ratio, and disease activity in children with juvenile ıdiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is a chronic inflammatory arthritis characterized by periods of remission and relapse. Mean platelet volume (MPV) is an indicator of systemic inflammation. In the present study, we aimed to determine the association between mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLR), platelet distribution width (PDW) and clinical measures of diseases activity in children with JIA. The study included 115 patients with JIA (64 with active disease and 51 with inactive disease) and 64 age-gender matched healthy control subjects. Routine laboratory methods were used to measure white blood cell count (WBC), platelet count (PLT), neutrophil count, lymphocyte count, hemoglobin (Hb), MPV, PDW, NLR, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in all subjects of both the patient and control groups. Active disease was associated with significantly increased MPV (8.23 ± 1.16 fl) compared with inactive disease (7.00 ± 1. 08 fl) and control subjects (6.77 ± 1.08 fl) P<0.001, P<0.001, P=NS, respectively). NLR was significantly higher in patients with active (2.11 ± 1.19) and inactive (2.03 ± 1.51) disease relative to the control subjects (1.33 ± 0.66) (P<0.001, P=0.017, respectively). Mean PDW was significantly higher in patients with active disease (17.84 ± 1.06) compared with the control group (17.19 ± 0.93) (P=0.01). Our results suggest that MPV may be a useful marker of disease activity in patients with JIA. Regular treatment may decrease platelet activation in JIA patients. However, NLR was not a predictive marker of disease activity in patients with JIA.


Seminal Fluid Metabolomic Markers of Oligozoospermic Infertility in Humans.
Infertility affects 12-15% of couples worldwide, and male factors are the cause of nearly half of all cases. Studying seminal fluid composition could lead to additional diagnostic accuracy and a better understanding of the pathophysiology of male factor infertility. Metabolomics offers a new opportunity to evaluate biomarkers and better understand pathological mechanisms. The aim of the study was to identify new markers or therapeutic targets to improve outcomes in male factor or idiopathic infertility patients. Semen samples were obtained from 29 men with a normal spermogram test, and from 18 oligozoospermic men. Samples were processed and analyzed by Nuclear Magnetic Resonance spectroscopy and, subsequently, multivariate and univariate statistical analyses. Receiving Operator Curves (ROC) and Spearman correlations were also performed. An Orthogonal Partial Least Square Discriminant Analysis supervised multivariate model was devised to compare the groups. The levels of fructose, myo-inositol, aspartate and choline were altered. Moreover, Spearman Correlation associated fructose, aspartate and myo-inositol with the total amount of spermatozoa, total motile spermatozoa, % of immotility and % of "in situ" spermatozoic motility respectively. NMR-based metabolomics allowed the identification of a specific metabolic fingerprint of the seminal fluids of patients affected by oligozoospermia.


Personal exposure to ultrafine particles.
Personal exposure to ultrafine particles (UFP) can occur while people are cooking, driving, smoking, operating small appliances such as hair dryers, or eating out in restaurants. These exposures can often be higher than outdoor concentrations. For 3 years, portable monitors were employed in homes, cars, and restaurants. More than 300 measurement periods in several homes were documented, along with 25 h of driving two cars, and 22 visits to restaurants. Cooking on gas or electric stoves and electric toaster ovens was a major source of UFP, with peak personal exposures often exceeding 100,000 particles/cm³ and estimated emission rates in the neighborhood of 10¹² particles/min. Other common sources of high UFP exposures were cigarettes, a vented gas clothes dryer, an air popcorn popper, candles, an electric mixer, a toaster, a hair dryer, a curling iron, and a steam iron. Relatively low indoor UFP emissions were noted for a fireplace, several space heaters, and a laser printer. Driving resulted in moderate exposures averaging about 30,000 particles/cm³ in each of two cars driven on 17 trips on major highways on the East and West Coasts. Most of the restaurants visited maintained consistently high levels of 50,000-200,000 particles/cm³ for the entire length of the meal. The indoor/outdoor ratios of size-resolved UFP were much lower than for PM₂.₅ or PM₁₀, suggesting that outdoor UFP have difficulty in penetrating a home. This in turn implies that outdoor concentrations of UFP have only a moderate effect on personal exposures if indoor sources are present. A time-weighted scenario suggests that for typical suburban nonsmoker lifestyles, indoor sources provide about 47% and outdoor sources about 36% of total daily UFP exposure and in-vehicle exposures add the remainder (17%). However, the effect of one smoker in the home results in an overwhelming increase in the importance of indoor sources (77% of the total).


Late recovery of renal failure after autologous haematopoietic stem cell transplantation for multiple myeloma: a report of two cases.
Acute renal failure is a frequent feature in patients with multiple myeloma (MM). MM-related renal insufficiency may improve after autologous haematopoietic stem cell transplantation (autoHSCT) even in patients initially requiring dialysis. Herein, we report on two unusual cases of late improvement in renal function occurring over more than 5 years after autoHSCT for MM. Clinicians must be aware that slow and progressive improvement in renal function may occur over years in patients with MM-associated renal failure. Our data underline the need for an aggressive treatment, including autoHSCT, in MM patients presenting with severe renal dysfunction.


Mutant APH(2'')-IIa enzymes with increased activity against amikacin and isepamicin.
Directed evolution by random PCR mutagenesis of the gene for the aminoglycoside 2''-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes, resulting in elevated levels of resistance to amikacin and isepamicin but not to other aminoglycoside antibiotics. Increases in the activities of the mutant phosphotransferases for isepamicin are the result of decreases in K(m) values, while improved catalytic efficiency for amikacin is the result of both a decrease in K(m) values and an increase in turnover of the antibiotic. Enzymes with R92H, D268N, and D268N single amino acid substitutions did not result in elevated MICs for aminoglycosides.


TORCH infection in women with bad obstetric history--a pilot study in Kumaon region.
TORCH infections in the mother are transmissible to fetus in the womb or during the birth process and cause a cluster of symptomatic birth defects. In mother they are inapparent or asymptomatic and hence difficult to diagnose clinically. Over a nine months period 20 pregnant women with bad obstetric history were-studied. Seropositivity of Toxoplasma, rubella, CMV, and HSV infections (TORCH) were demonstrated by the presence of IgM and IgG antibodies by ELISA method. It was found that, IgM antibodies were positive in 4 cases (20%) for Toxoplasma, 4 cases (28.6%) for rubella and 4 cases (26.7%) for CMV and HSV each. IgG antibodies were positive in 11cases (55%) for Toxoplasma, 10 cases (66.6%) for rubella, 14 cases (93%) for CMV and 11 (73%) for HSV. Therefore all antenatal cases with BOH should be routinely screened for TORCH as early diagnosis and appropriate intervention will help in proper management and fetal outcome.


[Establishment of A Serum-Free Culture System Based on Heparin and Anti-CD16 Antibody for Expansion of Human Cord Blood NK Cells].
To establish a novel method for ex vivo expansion of natural killer cells from human umbilical blood, so as to provide the basis for NK cell therapy. Mononucleated cells from human umbilical blood were harvested and suspended in a serum-free medium containing 5% autologous plasma, recombinant human IL-15 (50 ng/ml) and hydrocortisone sodium succinate (5×10-8 mol/L) at a concentration of 1.5×106/ml, then the cells were seeded into flasks pre-coated with heparin sodium (100 U/cm2) or/and anti-human CD16 antibody (1 µg/cm2). After culture for 2 weeks, the cells were harvested and counted. Ratios of CD3-/CD56+ of the cells were determined by flow cytometry. MTT test was performed to assess the cytotoxicity against K562 cells with graded ratios of effector/target cells. In contrast to the cells in flasks without pre-coating, the attached colonies appeared predominantly within 1 week of culture from heparin- and antibody-coated groups. The cell numbers from the pre-coated groups were significantly higher than that of uncoated one after culture for 2 weeks. Furthermore, the ratios of CD3-/CD56+ cells were much higher in pre-coated groups, and that of the cells from flasks pre-coated with heparin and antibody were the highest (all the P values <0.01). MTT test showed that the cytotoxic activity of the cells stimulated by precoating were much more potent than that of the cells without the stimulation. Advantageous expansion of NK cells can be achieved by precoating with heparin and anti-CD16 antibody, and also by supplement with IL-15 and hydrocortisone into the media, so the umbilical NK cells with high purity and potent cytotoxicity can be obtained.