A seat for premature infants.
Premature infants may benefit from short periods of supported sitting for position change, to facilitate the development of head control, to help with feeding and respiration, and to decrease intracranial pressure. This paper describes a seat designed for premature infants weighing 900 g to 2,000 g and made from thermoplastic material. The seats have been used with 30 infants with varying medical conditions.


Trastuzumab-decorated nanoparticles for in vitro and in vivo tumor-targeting hyperthermia of HER2+ breast cancer.
In this study, a magnetic core-shell modified tumor-targeting nanocarrier (MNPs-PEG-TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG-TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG-TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.


Hippocampal and orbital inferior frontal gray matter volume abnormalities and cognitive deficit in treatment-naive, first-episode patients with schizophrenia.
Cognitive impairment is a core feature of schizophrenia. Some evidence suggests an association between cognition deficits and gray matter reductions. In this study, we investigated the relationship between cognitive performance and gray matter volumes in patients with treatment-naïve, first-episode schizophrenia. First-episode patients with treatment-naïve schizophrenia and healthy controls went through brain imaging scan using high resolution magnetic resonance imaging. A neuropsychological battery including 8 neurocognitive tests was used to assess cognitive function. Voxel-based methods were used for volumetric measure in the brain. Fifty-one patients and 41 healthy controls were included in the analysis. Patients exhibited a poorer performance on all 7 cognitive function tests compared with healthy controls (ps<0.006). There were significant gray matter volume differences between the two groups in bilateral hippocampus gyri, right superior temporal gyrus, left fusiform gyrus and orbital inferior frontal gyri (FDR, ps<0.05). Within the schizophrenia group, multiple regression analysis demonstrated that poorer performance on the working memory, verbal learning and visual learning was associated with smaller hippocampal gray matter volume, and poorer executive function was associated with smaller left orbital inferior frontal gray matter volume after controlling for potential confounding variables (β ≥ 0.420, ps ≤ 0.010). Our findings suggest that cognitive deficits are associated with hippocampal and orbital inferior frontal gray matter volume abnormalities in treatment-naïve, first-episode patients with schizophrenia.


A media violence-inspired juvenile sexual homicide offender 13 years later.
No follow-up studies exist on how minors who commit sexual homicides adjust once released back into the community. This is an important question given the extreme nature of their crimes, lack of recidivism data, and the expectation that one-half of them will be freed from prison by mid-life. Likewise, no studies exist on the role our culture's pervasive media violence plays in these offenses. This report describes a 13-year-old boy who committed a witnessed media violence-inspired sexual homicide. Follow-up information is provided on his community adjustment as an adult four years after release from prison. He had multiple indicators of brain dysfunction, and watched a "slasher" film just before committing the blitz style crime upon a female neighbor. Media violence literature is reviewed--against a backdrop of developmental abnormalities, neuropsychiatric vulnerabilities, family dysfunction, and mental illness. This case illustrates how the confluence of such variables, combined with the tinder of erotic screen violence, may lead to sexual murder.


Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk factors.
To determine the rate of endophthalmitis in a group of patients with keratoprostheses and to analyze possible risk factors. A total of 108 patient eyes, operated on between 1990 and 2000 with double-plated keratoprostheses, were analyzed with regard to the surface flora, the incidence and cause of bacterial endophthalmitis or sterile vitreitis, the keratoprosthesis design, prophylactic antibiotics, concomitant immunosuppression, and preoperative diagnosis. Surveillance cultures were obtained from 30 uninfected eyes. The flora was similar to that reported in the normal population and did not vary significantly with time. Thirteen cases of bacterial endophthalmitis occurred 2 to 46 months postoperatively in the patient population that had been followed up for 2 months to 17 years (average, 3 years 4 months). The incidence was 39% in 13 patients with Stevens-Johnson syndrome, 19% in 27 patients with ocular cicatricial pemphigoid, and 7% in 28 patients with ocular burns. Only 1 of the other 40 cases (consisting mostly of repeated graft failures in noncicatrizing conditions) developed endophthalmitis; this patient had a filtering bleb. All endophthalmitis pathogens were gram positive: Streptococcus pneumoniae, 23%; other streptococci, 39%; Staphylococcus aureus, 23%; and Staphylococcus epidermidis, 15%. The most important risk factor for endophthalmitis after these keratoprostheses was found to be preoperative diagnosis. The rate of infection was very high in Stevens-Johnson syndrome and ocular cicatricial pemphigoid, moderate in chemical burns, and low in noncicatrizing corneal disease.


Infarct size limitation by the xanthine oxidase inhibitor, allopurinol, in closed-chest dogs with small infarcts.
The present study was designed to evaluate the ability of allopurinol to limit infarct size following permanent coronary occlusion in the greyhound. Coronary occlusion was produced by injecting 2.5 mm plastic beads into the coronary artery of the closed chest dog. Non-perfused myocardium, the area at risk, was visualised by autoradiography of 141Cerium labelled microspheres which were infused immediately following coronary embolization. The treated dogs (n = 12) received 400 mg of allopurinol orally one day before surgery. A 25 mg . kg-1 bolus was administered (iv) immediately before occlusion, and repeated every 8 h. 11 dogs served as controls. After 24 h, the dogs were killed and the hearts were sliced into 5.0 mm transverse sections. The infarcted myocardium was visualised by triphenyl tetrazolium chloride staining. The percentage of the risk zone which evolved to infarct was calculated. This percentage was 18.1 +/- 3.95% in the allopurinol group vs 58.4 +/- 2.81% in the control group (p less than 0.001). We conclude that allopurinol is a potent drug for the limitation of infarct size in the dog with permanent coronary occlusion.


Cardiovascular responses attenuate with repeated NO synthesis inhibition in conscious fetal sheep.
The cardiovascular effects of repeated administration of the nitric oxide (NO) synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) were assessed daily for 3 days in fetal sheep near term (124-126 days gestation) beginning 4 days after surgery (n = 7). In the first hour on day 1, fetal infusion of L-NAME (30 mg bolus, 6 mg/min infusion iv for 3 h) significantly increased fetal arterial pressure from 41 +/- 2 to 58 +/- 3 mmHg, decreased heart rate from 173 +/- 5 to 134 +/- 3 beats/min, increased umbilicoplacental resistance from 0.16 +/- 0.02 to 0.28 +/- 0.07 mmHg.ml-1.min, and inhibited the hypotensive response to acetylcholine (ACh; 2 micrograms iv bolus). All changes were sustained except for arterial pressure, which decreased significantly to 50 +/- 3 mmHg in the third hour. Within 17 h, all cardiovascular variables returned to control. L-NAME readministered on days 2 and 3 had no effect on cardiovascular variables. L-NAME did not potentiate the pressor response to angiotensin II on day 2 and caused a surprising attenuation of the pressor response to endothelin-1 on day 3. We conclude that, whereas NO normally contributes to low arterial pressure, high heart rate, and low umbilicoplacental vascular resistance in fetal sheep near term, the role of NO in these functions is replaced by an alternate mechanism within 17 h after NO synthesis inhibition with L-NAME.


Cortical and trabecular bone benefits of mechanical loading are maintained long term in mice independent of ovariectomy.
Skeletal loading enhances cortical and trabecular bone properties. How long these benefits last after loading cessation remains an unresolved, clinically relevant question. This study investigated long-term maintenance of loading-induced cortical and trabecular bone benefits in female C57BL/6 mice and the influence of a surgically induced menopause on the maintenance. Sixteen-week-old animals had their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse tibial axial compression loading model. Left tibias were not loaded and served as internal controls. Animals were subsequently detrained (restricted to cage activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX surgery being performed at 0 weeks detraining. Loading increased midshaft tibia cortical bone mass, size, and strength, and proximal tibia bone volume fraction. The cortical bone mass, area, and thickness benefits of loading were lost by 26 weeks of detraining because of heightened medullary expansion. However, loading-induced benefits on bone total area and strength were maintained at each detraining time point. Similarly, the benefits of loading on bone volume fraction persisted at all detraining time points. The long-term benefits of loading on both cortical and trabecular bone were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone properties at early (4 and 8 weeks) detraining time points and trabecular bone properties at all detraining time points. These cumulative data indicate loading has long-term benefits on cortical bone size and strength (but not mass) and trabecular bone morphology, which are not influenced by a surgically induced menopause. This suggests skeletal loading associated with physical activity may provide long-term benefits by preparing the skeleton to offset both the cortical and trabecular bone changes associated with aging and menopause.


Boron-Doped Nickel-Nitrogen-Carbon Single-Atom Catalyst for Boosting Electrochemical CO2 Reduction.
Tuning the coordination environment of the metal center in metal-nitrogen-carbon (M-N-C) single-atom catalysts via heteroatom-doping (oxygen, phosphorus, sulfur, etc.) is effective for promoting electrocatalytic CO2 reduction reaction (CO2 RR). However, few studies are investigated establishing efficient CO2 reduction by introducing boron (B) atoms to regulate the M-N-C structure. Herein, a B-C3 N4 self-sacrifice strategy is developed to synthesize B, N co-coordinated Ni single atom catalyst (Ni-BNC). X-ray absorption spectroscopy and high-angle annular dark field scanning transmission electron microscopy confirm the structure (Ni-N3 B/C). The Ni-BNC catalyst presents a maximum CO Faradaic efficiency (FECO ) of 98.8% and a large CO current density (jCO ) of -62.9 mA cm-2 at -0.75 and -1.05 V versus reversible hydrogen electrode, respectively. Furthermore, FECO could be maintained above 95% in a wide range of potential windows from -0.65 to -1.05 V. In situ experiments and density functional theory calculations demonstrate the Ni-BNC catalyst with B atoms coordinated to the central Ni atoms could significantly reduce the energy barrier for the conversion of *CO2 to *COOH, leading to excellent CO2 RR performance.


Dietary phosphorus and blood pressure: international study of macro- and micro-nutrients and blood pressure.
Raised blood pressure is a leading cause of morbidity and mortality worldwide; improved nutritional approaches to population-wide prevention are required. Few data are available on dietary phosphorus and blood pressure and none are available on possible combined effects of phosphorus, magnesium, and calcium on blood pressure. The International Study of Macro- and Micro-Nutrients and Blood Pressure is a cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population samples in Japan, China, United Kingdom, and United States. Blood pressure was measured 8 times at 4 visits. Dietary intakes were obtained from four 24-hour recalls plus data on supplement use. Dietary phosphorus was inversely associated with blood pressure in a series of predefined multiple regression models, with the successive addition of potential confounders, both nondietary and dietary. Estimated blood pressure differences per 232 mg/1000 kcal (2 SD) of higher dietary phosphorus were -1.1 to -2.3 mm Hg systolic/-0.6 to -1.5 mm Hg diastolic (n=4680) and -1.6 to -3.5 mm Hg systolic/-0.8 to -1.8 mm Hg diastolic for 2238 "nonintervened" individuals, ie, those without special diet/nutritional supplements or diagnosis/treatment for cardiovascular disease or diabetes. Dietary calcium and magnesium, correlated with phosphorus (partial r=0.71 and r=0.68), were inversely associated with blood pressure. Blood pressures were lower by 1.9 to 4.2 mm Hg systolic/1.2 to 2.4 mm Hg diastolic for people with intakes above versus below country-specific medians for all 3 of the minerals. These results indicate the potential for increased phosphorus/mineral intake to lower blood pressure as part of the recommendations for healthier eating patterns for the prevention and control of prehypertension and hypertension.


Glucagon release precedes insulin release in response to common secretagogues.
The dynamics and interrelationships of glucagon and insulin secretion were studied in the isolated perfused rat pancreas by utilizing a series of compounds that stimulate the release of both hormone. Leucine, arginine, prostaglandins F2alpha and E2, bovine growth hormone, and isoproterenol were administered individually over 60-second intervals. The release of glucagon preceded that of insulin in response to all compounds tested. The rapidity of glucagon release varied in response to different secretagogues; the time course of insulin release was fairly constant. The timing and the magnitude of glucagon and insulin release did not correlate statistically. (1) pancreatic alpha cells respond more rapidly than beta cells to the same stimulus; (2) antecedent release of glucagon is not the principal mediator of insulin release in response to stimuli common to both hormones; and (3) endogenous glucagon may at best modify the release of insulin evoked by certain secretagogues.


PEGylated Bilirubin-coated Iron Oxide Nanoparticles as a Biosensor for Magnetic Relaxation Switching-based ROS Detection in Whole Blood.
Rationale: Magnetic relaxation switching (MRSw) induced by target-triggered aggregation or dissociation of superparamagnetic iron oxide nanoparticles (SPIONs) have been utilized for detection of diverse biomarkers. However, an MRSw-based biosensor for reactive oxygen species (ROS) has never been documented. Methods: To this end, we constructed a biosensor for ROS detection based on PEGylated bilirubin (PEG-BR)-coated SPIONs (PEG-BR@SPIONs) that were prepared by simple sonication via ligand exchange. In addition, near infra-red (NIR) fluorescent dye was loaded onto PEG-BR@SPIONs as a secondary option for fluorescence-based ROS detection. Results: PEG-BR@SPIONs showed high colloidal stability under physiological conditions, but upon exposure to the model ROS, NaOCl, in vitro, they aggregated, causing a decrease in signal intensity in T2-weighted MR images. Furthermore, ROS-responsive PEG-BR@SPIONs were taken up by lipopolysaccharide (LPS)-activated macrophages to a much greater extent than ROS-unresponsive control nanoparticles (PEG-DSPE@SPIONs). In a sepsis-mimetic clinical setting, PEG-BR@SPIONs were able to directly detect the concentrations of ROS in whole blood samples through a clear change in T2 MR signals and a 'turn-on' signal of fluorescence. Conclusions: These findings suggest that PEG-BR@SPIONs have the potential as a new type of dual mode (MRSw-based and fluorescence-based) biosensors for ROS detection and could be used to diagnose many diseases associated with ROS overproduction.


LncRNA INHBA-AS1 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by sponging miR-143-3p.
Recent studies have revealed that long noncoding RNAs (lncRNAs) play important roles in the progression of tumorigenesis. Oral squamous cell carcinoma is a disease widely widespread all over the world. The aim of this study was to identify how lncRNA INHBA-AS1 functions in the progression of OSCC. LncRNA INHBA-AS1 expression in both OSCC cells and 48 paired tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The function of INHBA-AS1 was identified by the transwell assay, wound healing assay, and proliferation assay in vitro. Meanwhile, the role of INHBA-AS1 was investigated through tumor formation assay in vivo. Furthermore, the underlying mechanism was explored by the luciferase assays and RNA immunoprecipitation assay (RIP). INHBA-AS1 was highly expressed in OSCC tissues when compared with adjacent tissue samples. The proliferation, invasion, and migration of OSCC cells were significantly inhibited after the knockdown of INHBA-AS1 in vitro. Meanwhile, the knockdown of INHBA-AS1 remarkably inhibited tumor growth and metastasis in vivo. Besides, miR-143-3p was down-regulated after the knockdown of INHBA-AS1 in vitro. The expression of miR-143-3p was negatively correlated with the expression of INHBA-AS1 in OSCC tissues. In addition, miR-143-3p was directly targeted by INHBA-AS1. The knockdown of INHBA-AS1 repressed cell migration, invasion, and proliferation in OSCC by sponging miR-143-3p, which might offer a new therapeutic intervention for OSCC patients.


Training for an effective health and safety committee in a small business setting.
Health and safety committees are often heralded as a key element of successful health and safety programs, and are thought to represent a means of engaging workers in health and safety efforts. While the understanding of the factors that make these committees effective is growing, there are few resources for how to assist committees in developing these characteristics. This paper describes one approach to creating and implementing a training intervention aimed at improving health and safety committee function at one multilingual worksite. Short-term impacts were evaluated via questionnaire and qualitative observations of committee function. Results indicated high satisfaction with the training as well as modest increases in participation, cooperation, role clarity, and comfort with health and safety skills among committee members. The committee also made considerable achievements in establishing new processes for effective function. Similar interventions may be useful in other workplaces to increase health and safety committee success.


How do highly branched (colonial) mutants of Fusarium graminearum A3/5 arise during Quorn myco-protein fermentations?
Chlorate-resistant, highly branched (colonial) mutants and auxotrophic mutants were used to study the nuclear distribution, morphology and growth of heterokaryons of the Quorn myco-protein fungus, Fusarium graminearum A3/5. The results showed that for several complementary homokaryons, even a strong selective pressure was insufficient to maintain heterokaryons in a 'balanced' condition (i.e. exhibiting a wild-type or near wild-type phenotype). Furthermore, the margins of heterokaryotic colonies generally contained nuclei from only one of the parental homokaryons, indicating imperfect nuclear mixing within the mycelium. These observations suggest that recessive, colonial mutants may appear during Quorn myco-protein production following shear-induced separation of hyphal fragments which contain a sufficiently high ratio of colonial:wild-type nuclei for the colonial phenotype to be expressed.


Symbiotic System Establishment between Piriformospora indica and Glycine max and Its Effects on the Antioxidant Activity and Ion-Transporter-Related Gene Expression in Soybean under Salt Stress.
The utilization of symbiosis with beneficial microorganisms has considerable potential for increasing growth and resistance under abiotic stress. The endophytic root fungus Piriformospora indica has been shown to improve plant growth under salt and drought stress in diverse plant species, while there have been few reports of the interaction of P. indica with soybean under salt stress. In this study, the symbiotic system of P. indica and soybean (Glycine max L.) was established, and the effect of P. indica on soybean growth and salt tolerance was investigated. The colonized and non-colonized soybeans were subjected to salt stress (200 mmol/L NaCl), and the impairments in chlorophyll and increasing relative conductivity that can be caused by salt stress were alleviated in the P. indica-colonized plants. The accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2−) were lower than that in non-colonized plants under salt treatment, whereas the activities of antioxidant enzymes were significantly increased by P. indica colonization, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR). Importantly, without salt treatment, the Na+ concentration was lower, and the K+ concentration was higher in the roots compared with non-colonized plants. Differential expressions of ion transporter genes were found in soybean roots after P. indica colonization. The P. indica colonization positively regulated the transcription level of PM H+-ATPase, SOS1, and SOS2. The study shows that P. indica enhances the growth and salt tolerance of soybean, providing a strategy for the agricultural production of soybean plants in saline-alkali soils.


Mood effects on memory and executive control in a real-life situation.
In the laboratory, studies have shown an inconsistent pattern of whether, and how, mood may affect cognitive functions indicating both mood-related enhancement as well as decline. Surprisingly, little is known about whether there are similar effects in everyday life. Hence, the present study aimed to investigate possible mood effects on memory and executive control in a real-life situation. Mood effects were examined in the context of winning in a sports competition. Sixty-one male handball players were tested with an extensive cognitive test battery (comprising memory and executive control) both after winning a match and after training as neutral baseline. Mood differed significantly between the two testing situations, while physiological arousal and motivation were comparable. Results showed lowered performance after the win compared with training in selected cognitive measures. Specifically, short-term and episodic memory performance was poorer following a win, whereas executive control performance was unaffected by condition. Differences in memory disappeared when emotional states after the match were entered as covariates into the initial analyses. Thus, findings suggest mood-related impairments in memory, but not in executive control processes after a positive real-life event.


Reoperation for spinal restenosis in achondroplasia.
The characteristics of spinal restenosis in achondroplasia and its treatment are evaluated in this study. Radiologic and surgical findings were correlated to establish the causes of achondroplastic spinal restenosis and the benefits of its therapy. Eight patients (five men, three women) with spinal restenotic complications of achondroplasia were studied. The most common neurological sign of recurrent stenosis was impaired motor function. The mean interval between the most recent surgeries was 8.2 years (9.5 years for surgeries at the same levels). The most common causes of recurrent stenosis were facet hypertrophy and disk disease. The complications were a dural tear and cerebellar hemorrhage in one patient and transient neurological deterioration in another. One patient died after operation. Restenosis can occur many years after original decompression in the achondroplastic spine, and repeated operation can successfully lessen pain and neurological symptoms in most patients.


Nuclear inheritance of erythromycin resistance in human cells: new class of mitochondrial protein synthesis mutants.
The characterization of two new erythromycin-resistant mutants of HeLa cells is described. The strains ERY2305 and ERY2309 both exhibited resistance to erythromycin in growth assays and cell-free mitochondrial protein synthesis assays. The erythromycin resistance phenotype could not be transferred by cybridization. The mutation appeared to be encoded in the nucleus and inherited as a recessive trait. These two mutants, therefore, represent a new class of erythromycin-resistant mutants in human cells that is distinct from the cytoplasmically inherited mutation in strain ERY2301 described previously.


Responses of Nucleus Tractus Solitarius (NTS) early and late neurons to blood pressure changes in anesthetized F344 rats.
Previously, many different types of NTS barosensitive neurons were identified. However, the time course of NTS barosensitive neuronal activity (NA) in response to arterial pressure (AP) changes, and the relationship of NA-AP changes, have not yet been fully quantified. In this study, we made extracellular recordings of single NTS neurons firing in response to AP elevation induced by occlusion of the descending aorta in anesthetized rats. Our findings were that: 1) Thirty-five neurons (from 46 neurons) increased firing, whereas others neurons either decreased firing upon AP elevation, or were biphasic: first decreased firing upon AP elevation and then increased firing during AP decrease. 2) Fourteen neurons with excitatory responses were activated and rapidly increased their firing during the early phase of AP increase (early neurons); whereas 21 neurons did not increase firing until the mean arterial pressure changes (ΔMAP) reached near/after the peak (late neurons). 3) The early neurons had a significantly higher firing rate than late neurons during AP elevation at a similar rate. 4) Early neuron NA-ΔMAP relationship could be well fitted and characterized by the sigmoid logistic function with the maximal gain of 29.3. 5) The increase of early NA correlated linearly with the initial heart rate (HR) reduction. 6) The late neurons did not contribute to the initial HR reduction. However, the late NA could be well correlated with HR reduction during the late phase. Altogether, our study demonstrated that the NTS excitatory neurons could be grouped into early and late neurons based on their firing patterns. The early neurons could be characterized by the sigmoid logistic function, and different neurons may differently contribute to HR regulation. Importantly, the grouping and quantitative methods used in this study may provide a useful tool for future assessment of functional changes of early and late neurons in disease models.


Asymptomatic pediatric pulmonic valve myxoma involving the right ventricular outflow tract: a case report and review of the literature.
Asymptomatic pediatric pulmonic valve myxoma involving the right ventricular out flow tract (RVOT) is very rare. The case is presented of 13-year-old asymptomatic boy who was referred to the cardiology clinic for evaluation of murmur, and was found to have a large mobile mass (3 x 2 cm) in the RVOT that protruded into the pulmonary artery across the pulmonary valve during systole, and relocated in the right ventricle in diastole. The patient underwent successful surgical excision of the tumor, which had a short stalk attached to the pulmonary valve. Macroscopic examination revealed a typical myxoma without any evidence of malignancy. This case elaborates the importance of early recognition and surgical excision of these tumors in order to prevent thromboembolic complications.


Chlamydia pneumoniae not detected in temporal artery biopsies from patients with temporal arteritis.
In a recent report Chlamydia pneumoniae (C. pneumoniae), examined with both immunohistochemistry and polymerase chain reaction (PCR), was detected in positive temporal artery biopsies from patients with temporal arteritis (TA). Our aim was to examine whether C. pneumoniae could be detected in patients with TA recruited from a high endemic area of TA in southern Norway. Twenty paraffin-embedded temporal artery biopsies showing convincing inflammation in the vessel wall with lymphocytic infiltration (giant cells in 12 biopsies) from 20 patients with TA were examined for the presence of C. pneumoniae using an established PCR technique. All examined TA patients (mean age 74.4 (SD 7.5) years, 75% females) fulfilled the ACR-1990 criteria. C. pneumoniae was not detected in any of the biopsies. In conclusion, our results indicate that C. pneumoniae, at least in the population of southern Norway, does not have any pathogenetic role in TA.


Knowledge, attitude, and practices of family planning methods among married women from a rural area of Jaipur, Rajasthan: An observational study.
This study was planned with the objective to assess the knowledge, attitude, and practices of family planning methods among married women and to find out the factors associated with not using the family planning method. This community-based cross-sectional observational study was conducted in 300 married women residing in a rural area of Jaipur, Rajasthan. Written informed consent was obtained, and data were collected using a pre-tested semi-structured questionnaire. Knowledge, attitude, and practices were summarised in proportion, and their association was measured using Chi-square test. The mean age of the participants was 26.7 years. Most of them (88.8% women) had knowledge of at least one contraception method. Almost two-thirds had positive attitude towards contraceptive use. The most used method was oral contraceptive pills, among 17.7% of participants. Knowledge was significantly associated with educational level and caste of the participants (P value <0.05), and practice was not significantly associated with any socio-demographic factors (P value >0.05). Knowledge, attitude, and practices related to modern family planning methods are still not high in rural areas. The media can play a major role in increasing awareness about family planning methods. The involvement of community and family, especially spouse, should be facilitated to maximize the understanding of family planning methods.


Differing levels of clinical evidence: exploring communication challenges in shared decision making. Introduction.
The near ubiquitous access to information is transforming the roles and relationships among clinical professionals, patients, and their care givers in nearly all aspects of healthcare. Informed patients engage their physicians in conversations about their conditions, options and the tradeoffs among diagnostic and therapeutic benefits and harms. The processes of care today increasingly and explicitly integrate exploration of patient values and preferences as patients and clinicians jointly engage in reaching decisions about care. The informed patient of today who can understand and use scientific information can participate as an equal partner with her clinician. Others with beliefs or educational, cultural, or literacy backgrounds that pose challenges to comprehending and applying evidence may face disenfranchisement. These barriers are significant enough, even in the face of certainty of evidence, that clinicians and investigators have given much thought to how best to engage all patients in decision making. However, barriers remain, as most decision making must occur in settings where uncertainty, if not considerable uncertainty, accompanies any statement of what we know. In September 2011, health care and health communication experts came together in Rockville, Maryland under the auspices of the Agency for Healthcare Research and Quality (AHRQ) John M. Eisenberg Center for Clinical Decisions and Communications Science Annual Meeting to explore the challenges of differing levels of evidence in promoting shared decisions and to propose strategies for going forward in addressing these challenges. Eight scholarly papers emerged, and with this introductory article, comprise this special issue of Medical Care Research and Review.


Hollow nanospheres constructed by CoS2 nanosheets with a nitrogen-doped-carbon coating for energy-storage and photocatalysis.
Hierarchical CoS2 hollow nanospheres (HSs) with a nitrogen-doped-carbon coating (NC@CoS2 ) are fabricated by a simple solution method. The uniform 300 nm-sized NC@CoS2 HSs are composed of ultrathin nanosheet subunits with a thickness of around 2 nm. It was found that polyvinylpyrrolidone and ethylenediamine not only controlled the morphology of the products, but also provided the sources of nitrogen-doped carbon. Benefiting from their unique structural characteristics, hierarchical NC@CoS2 HSs can be applied in lithium-ion batteries, supercapacitors, and photocatalysis. When evaluated as an electrode material, NC@CoS2 with a coating of optimal thickness showed a high lithium-storage capability with a good cycling stability. Moreover, NC@CoS2 had a remarkable supercapacitive performance and photocatalytic activity. The attractive electrochemical and photocatalytic performances were attributed to the overall structural features of the NC@CoS2 hollow spheres: the N-doped-carbon (NC) coating, hollow interior, and ultrathin nanosheets.


Trajectory of post-traumatic stress following traumatic injury: 6-year follow-up.
Traumatic injuries affect millions of patients each year, and resulting post-traumatic stress disorder (PTSD) significantly contributes to subsequent impairment. To map the distinctive long-term trajectories of PTSD responses over 6 years by using latent growth mixture modelling. Randomly selected injury patients (n = 1084) admitted to four hospitals around Australia were assessed in hospital, and at 3, 12, 24 and 72 months. Lifetime psychiatric history and current PTSD severity and funxctioning were assessed. Five trajectories of PTSD response were noted across the 6 years: (a) chronic (4%), (b) recovery (6%), (c) worsening/recovery (8%), (d) worsening (10%) and (e) resilient (73%). A poorer trajectory was predicted by female gender, recent life stressors, presence of mild traumatic brain injury and admission to intensive care unit. These findings demonstrate the long-term PTSD effects that can occur following traumatic injury. The different trajectories highlight that monitoring a subset of patients over time is probably a more accurate means of identifying PTSD rather than relying on factors that can be assessed during hospital admission.


Closed fractures complicated by acute hematogenous osteomyelitis.
Osteomyelitis developed at closed fracture sites in two children. The infection responded to antibiotic therapy, and the fractures healed without chronic infection developing, impairment of bone growth, or loss of function. It is rare for a closed fracture to develop acute hematogenous osteomyelitis, but the diagnosis should be considered in a child with a closed fracture in whom a fever develops or who complains of increasing pain after the fracture has been reduced and immobilized. In children, the condition has an excellent prognosis.


Hodgkin's lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis.
In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than do younger ones. Inadequate therapy, often due to decreased tolerance to treatment, contributes to the poor outcome. This study was undertaken to evaluate potential clinical factors of importance for prognosis with special reference to relative dose intensity (RDI) of chemotherapy (CT). Eighty-eight consecutive elderly (>60 years) HL patients diagnosed between 1973-1994 who received up-front CT+/-radiotherapy (RT) were included (median age 72 years, range 60-92; median follow-up time 78 months, range 49-206). The calculations of RDI of CT were based on Hryniuk's model. The 5-year overall (OS) and cause-specific (CSS) survival was 39% and 51%, respectively, in patients who received CT+/-RT. Nine of the 14 patients who only received 1 cycle of CT died within 6 months from diagnosis without achieving complete remission (CR). However, the remaining 5 patients in this group survived 14-97+ months. Patients with a RDI >65% had a significantly better OS (p=0.029) and CSS (p=0.024) than those with a RDI 65%. Patients who received ABVD-based CT with a RDI >65% had a significantly better OS (p=0.0011) than those who were treated with ABVD-based CT with a RDI 65%, or MOPP-like therapy, irrespective of received RDI. Prognosis remains heterogeneous and the significance of established prognostic factors is limited in elderly HL patients. Patients who received a low RDI of CT and those receiving non-ABVD-based treatment fared worse. However, also elderly patients can enjoy long-standing complete remission following minimal treatment.


Proteolytic degradation of MAD3 (I kappa B alpha) and enhanced processing of the NF-kappa B precursor p105 are obligatory steps in the activation of NF-kappa B.
We have studied the role of protein turnover in the induction of NF-kappa B DNA binding activity. Treatment of cells with tumour necrosis factor (TNF), double-stranded RNA (dsRNA), or phorbol esters is shown to be associated with an increase in the rate of p105 to p50 processing, and the loss of immunologically detectable MAD3/I kappa B alpha. Phosphate-labelling experiments indicate that these events are preceded by the phosphorylation of MAD3 and p105. The protease inhibitors TLCK (N alpha-p-Tosyl-L-Lysine Chloromethyl Ketone) and TPCK (N alpha-p-Tosyl-L-Phenylalanine Chloromethyl Ketone) inhibit both p105 to p50 processing and MAD3 degradation, and also cause a complete block to NF-kappa B activation. These data suggest a model for NF-kappa B activation in which phosphorylation destabilises the NF-kappa B/MAD3 complex but that, in vivo, this is insufficient to lead to activation in the absence of an obligatory mechanism that degrades MAD3.


European organic dairy farmers' preference for animal health management within the farm management system.
The expertise and knowledge of veterinary advisors on improving animal health management is key towards a better herd health status. However, veterinary advisors are not always aware of the goals and priorities of dairy farmers. To dairy farmers animal health is only one aspect of farm management and resources may be allocated to other more preferred areas. Veterinary advisors may experience this as non-compliant with their advice. To explore the preferences of European Union (EU) organic dairy farmers for improved animal health management relative to other farm management areas an adaptive conjoint analysis (ACA) was performed. A total of 215 farmers participated originating from organic dairy farms in France (n = 70), Germany (n = 60), Spain (n = 28) and Sweden (n = 57). The management areas udder health and claw health represented animal health management whereas barn, calf and pasture management represented potential conflicting management areas. Results indicate that EU organic dairy farmers differ in their preferences for improved animal health management within the farming system. In general, improved calf management was the most preferred area and improved claw health management was found to be least preferred, the remaining areas were of intermediate interest. Cluster analyses on claw health measures and udder health measures resulted in respectively seven and nine distinct preference profiles. The results indicate a high degree of variation in farmers' preference, which cannot be explained by the typical herd characteristics. With the individual preferences revealed by ACA, a veterinary advisor can now find out whether his intended advice is directed at a favourable or unfavourable management area of the farmer. If the latter is the case the veterinarian should first create awareness of the problem to the farmer. Insights in individual farmers preferences will allow veterinary advisors to better understand why farmers were incompliant with their advice and improve their advice by showing, for example, the potential benefits of their advice.


Low-frequency fluctuations in two-state quantum dot lasers.
We study the feedback-induced instabilities in a quantum dot semiconductor laser emitting in both ground and excited states. Without optical feedback the device exhibits dynamics corresponding to antiphase fluctuations between ground and excited states, while the total output power remains constant. The introduction of feedback leads to power dropouts in the ground state and intensity bursts in the excited state, resulting in a practically constant total output power.


Revising the common understanding of metamagnetism in the molecule-based bisdithiazolyl BDTMe compound.
The BDTMe molecule-based material is the first example of a thiazyl radical to exhibit metamagnetic behavior. Contrary to the common idea that metamagnetism occurs in low-dimensional systems, it is found that BDTMe magnetic topology consists of a complex 3D network of almost isotropic ferromagnetic spin-ladders that are coupled ferromagnetically and further connected by some weaker antiferromagnetic interactions. Calculated magnetic susceptibility χT(T) data is in agreement with experiment. Calculated M(H) data clearly show the typical sigmoidal shape of a metamagnet at temperatures below 2 K. The calculated critical field becomes more apparent in the dM/dH(H) plot, being in very good agreement with experiment. Our computational study concludes that the magnetic topology of BDTMe is preserved throughout the entire experimental range of temperatures (0-100 K). Accordingly, the ground state is the same irrespective of the temperature at which we study the BDTMe crystal. Revising the commonly accepted understanding of a metamagnet explained as ground state changing from antiferromagnetic to ferromagnetic, the Boltzmann population of the different states is here suggested to be the key concept: at 2 K the ground singlet state has more weight (24%) than at 10 K (1.5%), where excited states have an important role. Changes in the antiferromagnetic interactions that couple the ferromagnetic skeleton of BDTMe will directly affect the population of the distinct states that belong to a given magnetic topology and thus its magnetic response. Accordingly, this strategy could be valid for a wide range of bisdithiazolyl BDT-compounds whose magnetism can be tuned by means of weak antiferromagnetic interactions.


Multiple transient memories in experiments on sheared non-Brownian suspensions.
A system with multiple transient memories can remember a set of inputs but subsequently forgets almost all of them, even as they are continually applied. If noise is added, the system can store all memories indefinitely. The phenomenon has recently been predicted for cyclically sheared non-Brownian suspensions. Here we present experiments on such suspensions, finding behavior consistent with multiple transient memories and showing how memories can be stabilized by noise.


Clinical and electrodiagnostic correlates of peroneal intraneural ganglia.
Intraneural ganglia (IG) are an underappreciated but treatable cause of common peroneal neuropathy (CPN). This study was designed to determine if there are clinical measures that distinguish CPN caused by IG from CPN without a clear proximate cause. Clinical and electrodiagnostic features of 22 cases of IG were compared in a case-control study to 11 cases of CPN with imaging negative for IG. The IG group had a greater body mass index (30 vs 24; p < 0.005), more pain at the knee (52% of 22 vs 0% of 11; p < 0.005) or in the peroneal distribution (76% of 21 vs 27% of 1; p < 0.02), more frequent fluctuating weakness (48% of 21 vs 4% of 29; p < 0.01) with weight bearing (38%, p < 0.05), or a palpable mass (47% of 20, p < 0.01) at the fibular head. The IG group was less likely to present with a history of weight loss (0% vs 36%; p < 0.01), immobility (0% vs 21%; p < 0.03), or leg crossing (0% vs 80%; p < 0.05). There were no significant electrophysiologic differences. Presenting clinical features increase the likelihood of intraneural ganglia and may assist selection of patients with common peroneal neuropathy for diagnostic peroneal nerve imaging.


Hormonal regulation of phosphatidylinositol breakdown.
Cyclic AMP and Ca2+ are intracellular mediators of hormone action. Catecholamines interact with beta adrenoceptors to activate adenylate cyclase or with alpha 2 adrenoceptors to inhibit adenylate cyclase. Alpha 1 adrenoceptor activation results in elevation of cytosol Ca2+ and an increased breakdown of phosphatidylinositol. In blowfly salivary glands, 5-hydroxytryptamine (5-HT) interacts with beta type receptors resulting in adenylate cyclase activation while alpha type receptors are involved in phosphatidylinositol breakdown and elevation of cytosol Ca2+. The link between Ca2+ mobilization and phosphatidylinositol breakdown remains to be established but breakdown of the receptor-regulated pool of phosphatidylinositol is not secondary to the rise in Ca2+. Direct addition of 5-HT to cell-free homogenates of blowfly salivary glands results in activation of phosphatidylinositol breakdown in the absence of Ca2+. In rat liver plasma membrane preparations, vasopressin increases phosphatidylinositol breakdown in the absence of Ca2+ or cytosol if deoxycholate is present. The data do not indicate whether hormone activation increases the availability of substrate to enzymatic hydrolysis or activates phospholipase C. However, they demonstrate that hormones directly accelerate phosphatidylinositol breakdown.


Altered DNA methylation is associated with aberrant stemness gene expression in early‑stage HNSCC.
Head and neck squamous cell carcinoma (HNSCC) is characterized by morphological and functional cellular heterogeneity, which are properties of progenitor cells, as opposed to cell alterations caused by accidental expression of stem cell‑related molecules. The expression levels of stemness molecules and their distribution in HNSCC are unclear. As regards sporadic cellular heterogeneity, methylation is an important factor for transcriptional regulation in tumors. Integrative screening analysis of mRNA expression and altered methylation status was performed with original microarrays in 12 tumor and non‑tumor pairs of oral squamous cell carcinoma (SCC) cases. From this data set, genes regulated via aberrant DNA methylation and classified proteins were validated by function clustering. Olfactomedin 4 (OLFM4), known as an intestinal stemness molecule and cell‑cell adhesion factor, was found to be highly expressed in tumors, with an mRNA expression ratio [tumor/normal (T/N)] of 40.7686 and low methylation (‑18.02%) in the promoter region. In addition, the OLFM4 expression levels increased following treatment with the demethylating agent 5‑azacytidine in two HNSCC cell lines. Furthermore, the expression levels of OLFM4 in 59 cases of early‑stage tongue SCC were analyzed using immunohistochemistry to examine protein expression corresponding to the histopathological definition of tumors and to evaluate prognosis. The aberrant stemness gene expression caused by altered DNA methylation appeared to regulate early‑stage HNSCC characteristics. The results of the present study indicated a correlation between OLFM4 expression and promoter methylation, and suggest that it plays an important role in tumor cell heterogeneity in HNSCC.


A gene signature to determine metastatic behavior in thymomas.
Thymoma represents one of the rarest of all malignancies. Stage and completeness of resection have been used to ascertain postoperative therapeutic strategies albeit with limited prognostic accuracy. A molecular classifier would be useful to improve the assessment of metastatic behaviour and optimize patient management. qRT-PCR assay for 23 genes (19 test and four reference genes) was performed on multi-institutional archival primary thymomas (n = 36). Gene expression levels were used to compute a signature, classifying tumors into classes 1 and 2, corresponding to low or high likelihood for metastases. The signature was validated in an independent multi-institutional cohort of patients (n = 75). A nine-gene signature that can predict metastatic behavior of thymomas was developed and validated. Using radial basis machine modeling in the training set, 5-year and 10-year metastasis-free survival rates were 77% and 26% for predicted low (class 1) and high (class 2) risk of metastasis (P = 0.0047, log-rank), respectively. For the validation set, 5-year metastasis-free survival rates were 97% and 30% for predicted low- and high-risk patients (P = 0.0004, log-rank), respectively. The 5-year metastasis-free survival rates for the validation set were 49% and 41% for Masaoka stages I/II and III/IV (P = 0.0537, log-rank), respectively. In univariate and multivariate Cox models evaluating common prognostic factors for thymoma metastasis, the nine-gene signature was the only independent indicator of metastases (P = 0.036). A nine-gene signature was established and validated which predicts the likelihood of metastasis more accurately than traditional staging. This further underscores the biologic determinants of the clinical course of thymoma and may improve patient management.


[Endometrial and ovarian tumours and their association with obesity].
A 53-year-old woman was wheelchair-dependent and unable to work due to an extreme increase in abdominal circumference. Closer investigation revealed an ovarian tumour. A mucinous cystadenoma of the ovary weighing more than 20 kg was removed with laparotomy. A 63-year-old woman presented with postmenopausal haemorrhage. Morbid obesity and agoraphobia had prevented her from visiting a doctor earlier. She was eventually diagnosed with stage 1C grade III endometrial carcinoma, which was treated with surgery and vaginal brachytherapy. The incidence of gynaecological tumours is increased in patients with a high BMI. This association is stronger for endometrial carcinoma than for ovarian carcinoma. Obesity has a favourable influence on the histological grade of endometrial carcinoma, and is associated with lower-stage ovarian cancer. Surgery-related complications are more common in obese patients. Determining the optimal dose of adjuvant therapy is also problematic in obese patients.


Nonpharmacologic approach to fatigue in patients with cancer.
Cancer-related fatigue is a common yet underappreciated problem with a significant impact on functional ability and quality of life. Practice guidelines mandate that all cancer patients and survivors be screened for cancer-related fatigue (CRF) at regular intervals. Comorbidities that could contribute to fatigue should be treated, and patients with moderate to severe fatigue should undergo a comprehensive evaluation. Nonpharmacologic interventions are important tools to combat CRF and should be incorporated into routine practice. Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. From a practical standpoint, general education on CRF is something that most care providers can readily offer patients as part of routine care. Other interventions that appear promising but are as yet lacking convincing evidence include mindfulness-based stress reduction, yoga, and acupuncture. Reiki, Qigong, hypnosis, and music therapy may be worthy of further investigation.


[Effect of flavin coenzymes on the pyridoxine treatment of avitaminosis B6].
Studies on rats with experimental vitamin B6 deficiency have shown that the combined use of pyridoxine and flavine coenzymes affects the supply of rats with these vitamins. Flavine coenzymes have been found to promote more efficient normalization of pyridoxine and riboflavin balance in the body and to improve the general status of the animals, to increase the excretion of riboflavin and 4-pyridoxic acid with urine, to prove more rapid cure of vitamin deficiency.


Measures of quantum synchronization in continuous variable systems.
We introduce and characterize two different measures which quantify the level of synchronization of coupled continuous variable quantum systems. The two measures allow us to extend to the quantum domain the notions of complete and phase synchronization. The Heisenberg principle sets a universal bound to complete synchronization. The measure of phase synchronization is, in principle, unbounded; however, in the absence of quantum resources (e.g., squeezing) the synchronization level is bounded below a certain threshold. We elucidate some interesting connections between entanglement and synchronization and, finally, discuss an application based on quantum optomechanical systems.


Decomposition mechanism of α-alkoxyalkyl-hydroperoxides in the liquid phase: temperature dependent kinetics and theoretical calculations.
Organic hydroperoxides (ROOHs) play key roles in the atmosphere as a reactive intermediate species. Due to the low volatility and high hydrophilicity, ROOHs are expected to reside in atmospheric condensed phases such as aerosols, fogs, and cloud droplets. The decomposition mechanisms of ROOHs in the liquid phase are, however, still poorly understood. Here we report a temperature-dependent kinetics and theoretical calculation study of the aqueous-phase decompositions of C12 or C13 α-alkoxyalkyl-hydroperoxides (α-AHs) derived from ozonolysis of α-terpineol in the presence of 1-propanol, 2-propanol, and ethanol. We found that the temporal profiles of α-AH signals, detected as chloride-adducts by negative ion electrospray mass spectrometry, showed single-exponential decay, and the derived first-order rate coefficient k for α-AH decomposition increased as temperature increased, e.g., k(288 K) = (5.3 ± 0.2) × 10-4 s-1, k(298 K) = (1.2 ± 0.3) × 10-3 s-1, k(308 K) = (2.1 ± 1.4) × 10-3 s-1 for C13 α-AHs derived from the reaction of α-terpineol Criegee intermediates with 1-propanol in the solution at pH 4.5. Arrhenius plot analysis yielded an activation energy (E a) of 12.3 ± 0.6 kcal mol-1. E a of 18.7 ± 0.3 and 13.8 ± 0.9 kcal mol-1 were also obtained for the decomposition of α-AHs (at pH 4.5) derived from the reaction of α-terpineol Criegee intermediates with 2-propanol and with ethanol, respectively. Based on the theoretical kinetic and thermodynamic calculations, we propose that a proton-catalyzed mechanism plays a central role in the decomposition of these α-AHs in acidic aqueous organic media, while water molecules may also participate in the decomposition pathways and affect the kinetics. The decomposition of α-AHs could act as a source of H2O2 and multifunctionalized species in atmospheric condensed phases.


Dynamical screening and excitonic instability in bilayer graphene.
Electron interactions in undoped bilayer graphene lead to an instability of the gapless state, "which-layer" symmetry breaking, and energy gap opening at the Dirac point. In contrast with single-layer graphene, the bilayer system exhibits instability even for an arbitrarily weak interaction. A controlled theory of this instability for realistic dynamically screened Coulomb interactions is developed, with full account of the dynamically generated ultraviolet cutoff. This leads to an energy gap that scales as a power law of the interaction strength, making the excitonic instability readily observable.


Mast cell density, hepatic stellate cell activation and TGF-beta1 transcripts in the aging Sprague-Dawley rat during early acute liver injury.
Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CCl4) toassess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-beta1, hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-beta1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion. MC density may be an index of acute liver inflammation after CCl4 intoxication.


Correlations between polyamine analogue-induced increases in spermidine/spermine N1-acetyltransferase activity, polyamine pool depletion, and growth inhibition in human melanoma cell lines.
The polyamine analogue, N1,N12-bis(ethyl(-spermine (BESPM), is known to suppress ornithine and S-adenosylmethionine decarboxylase levels, deplete intracellular polyamine pools, and inhibit cell growth. Among human melanoma cell lines, MALME-3 cells were found to be typically sensitive to the antiproliferative activity of the BESPM, whereas LOX cells were atypically insensitive to the analogue. A comparison of polyamine-related parameters revealed that the most differentially altered activity between the 2 BESPM-treated cell lines was that of spermidine/spermine N1-acetyltransferase (SSAT), which increased from 50 pmol/min/mg to greater than 10,000 pmol/min/mg in MALME-3 cells and from 16 pmol/min/mg to only 120 pmol/min/mg in LOX cells over 48 h. The basis for the large difference seems to be related to increased enzyme synthesis in both cell lines coupled with differences in prolongation of SSAT half-life (greater than 12 h in MALME-3 cells versus 1.6 h in LOX cells) after BESPM treatment. In MALME-3 cells, SSAT accumulation was found to be differentially modulated by the BESPM homologues, N1,N11-bis-(ethyl)norspermine and N1,N14-bis-(ethyl)homospermine, which were 5-fold more and 9-fold less effective, respectively, than BESPM in increasing SSAT but similar in analogue uptake and effects on polyamine biosynthesis and cell growth inhibition. Treatment of MALME-3 cells with BESPM resulted in an accumulation of N-acetylspermidine in cells and the enhanced excretion of putrescine, spermidine, and N-acetylspermidine into the medium. The relationship between SSAT induction and growth sensitivity was deduced to be a possible function of increased excretion of acetylated polyamines leading to enhanced polyamine pool depletion. The data suggest that, in cell types in which it occurs, unusually high increases in SSAT activity may serve as a determinant of growth sensitivity to bis-ethyl spermine analogues or, alternatively, as a target for appropriately designed chemotherapeutic strategies.


Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors.
A Phase I-II trial of gallium nitrate was conducted in 40 patients with bidimensionally measurable urothelial tract tumors who had failed to respond to combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional patients who received 350 mg/m2/d or more, a minor response and a mixed response were observed. The median duration of response was 4 months (range, 2 to 8 months). A dose-response relationship was suggested because no responses were observed in 17 patients who received less than 350 mg/m2/d. Myelosuppression was minimal. The dose-limiting toxic reaction was a reversible optic neuropathy that occurred in 3 of 11 patients who received 400 mg/m2/d. Further evaluation of infusional gallium nitrate is warranted in patients with urothelial tract malignant tumors.


Accurate flow cytometric membrane potential measurement in bacteria using diethyloxacarbocyanine and a ratiometric technique.
Membrane potential (MP) plays a critical role in bacterial physiology. Existing methods for MP estimation by flow cytometry are neither accurate nor precise, due in part to the heterogeneity of size of the particles analyzed. The ratio of a size- and MP-sensitive measurement, and an MP-independent, size-sensitive measurement, should provide a better estimate of MP. Flow cytometry and spectrofluorometry were used to detect red (488 --> 600 nm) fluorescence associated with aggregates of diethyloxacarbocyanine (DiOC2(3)), which, in the monomeric state, is normally green (488 --> 530 nm) fluorescent. In bacteria incubated with 30 microM dye, aggregate formation increases with the magnitude of the interior-negative membrane potential. Green fluorescence from stained bacteria predominantly reflects particle size, and is relatively independent of MP, whereas red fluorescence is highly dependent on both MP and size. The ratio of red to green fluorescence provides a measure of MP that is largely independent of cell size, with a low coefficient of variation (CV). Calibration with valinomycin and potassium demonstrates that the method is accurate over the range from -50 mV through -120 mV; it also accurately tracks reversible reductions in MP produced by incubation at 4 degrees C and washing in glucose-free medium. The ratiometric technique for MP estimation using DiOC2(3) is substantially more accurate and precise than those previously available, and may be useful in studies of bacterial physiology and in investigations of the effects of antibiotics and other agents on microorganisms.


Physician review websites: effects of the proportion and position of negative reviews on readers' willingness to choose the doctor.
Health consumers are increasingly turning to physician review websites to research potential health care providers. This experiment examined how the proportion and position of negative reviews on such websites influence readers' willingness to choose the reviewed physician. A 5 × 2 (Proportion of Negative Reviews × Position of Negative Reviews) factorial design was implemented, augmented with two standalone comparison groups. Five hundred participants were recruited through a crowdsource website and were randomly assigned to read a webpage screenshot corresponding to 1 of 12 experimental conditions. The participants then completed a questionnaire that assessed evaluations of and cognitive elaborations (thoughts) about the physician. The authors hypothesized that readers would be less willing to use a physician's services when reviews were predominantly negative and negative comments were positioned before positive comments. As hypothesized, an increase in the proportion of negative reviews led to a reduced willingness to use the physician's services. However, this effect was not moderated by the level of cognitive elaboration. A primacy effect was found for negative reviews such that readers were less willing to use the physician's services when negative reviews were presented before positive reviews, rather than after. Implications for future research are discussed.


Frequency of undetected thyroid nodules in a large I-131-exposed population repeatedly screened by ultrasonography: results from the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases following the Chornobyl accident.
Imperfect detection on screening tests can lead to erroneous conclusions about the natural history of thyroid nodules following radiation exposure. Our objective was to assess in a repeatedly screened I-131-exposed population the frequency with which a thyroid nodule could be retrospectively identified on ultrasonography studies preceding the one on which it was initially detected. A cohort of over 13,000 young people exposed to fallout from Chornobyl underwent ultrasonography screening at 2-year intervals from 1998 to 2007. The study group consisted of screening examinations on which a thyroid nodule was detected following one or more prior negative examinations. In the study group there were 48 cancers and 92 benign nodules. For each of these 140 index studies a comparison set was created containing all available prior studies plus (to test for bias) negative studies from control subjects. While viewing the index study, three independent reviewers scored the comparison studies for the presence and size of a preexisting nodule. Detection rates were compared for true priors versus controls, for cancer versus benign, and for histologic subtypes of papillary carcinoma. A preexisting nodule was identified by at least one reviewer in 24.0% of the true prior versus 8.3% of the controls and by all three reviewers in 11% versus 1% (Fisher's exact test, p < 0.0001). There was no significant difference in detection rates between cancers and benign nodules (22.4% vs. 24.7%, p = 0.411). There was no correlation between time from prior to index study and change in nodule size for either malignant or benign nodules (r = 0.01, NS). There were no differences in detection rates or size among papillary cancer subtypes. Reviewers could not distinguish between true priors and controls. These findings, showing significant rates of undetected benign and malignant nodules and no evidence for rapid growth, suggest that conclusions drawn from screening studies about the frequency of late-developing, rapidly growing thyroid nodules following radiation exposure should be interpreted with caution.


[Biopercular syndrome: report of two cases and literature review].
The anterior opercular or biopercular syndrome is a cortical pseudobulbar palsy due to bilateral lesions of the anterior brain operculum. It is characterized by preservation of reflex function and automatic activity, without mental impairment. Two cases are reported herein and the relevant literature reviewed. The first case was a 73-year-old female with a history of a stroke occurring seven years previously, without sequelae in the interim. She presented with sudden loss of consciousness. The neurological examination showed a right facial central palsy and anarthria, with reflex acts such as smiling, blinking and yawning, not elicited by commands; she also had a right hemiparesis and walking impairment. A brain CT scan showed an old ischemic infarction in the region of the right medial cerebral artery. Because the right motor involvement did not correlate with the findings of the initial CT scan, another CT scan two days later showed an acute brain infarction in the vicinity of the left medial cerebral artery. The second case was an 8-year-old girl with mental retardation and impairment of verbal development, caused by of biopercular pachygyria. Facio-pharyngo-glosso-masticatory diplegia and volitional selective palsy of the oro-facial muscles was seen in both patients. The neuropsychological assessment showed cognitive, emotional and social interaction impairment in both cases -as part of the frontal convexity syndrome in the first case and of mental retardation in the second. The two patients had difficulty in mastication and swallowing. The prognosis for recovery of verbal capacity is poor, although generally most patients recover the ability to swallow.


Hydroxamate production as a high affinity iron acquisition mechanism in Paracoccidioides spp.
Iron is a micronutrient required by almost all living organisms, including fungi. Although this metal is abundant, its bioavailability is low either in aerobic environments or within mammalian hosts. As a consequence, pathogenic microorganisms evolved high affinity iron acquisition mechanisms which include the production and uptake of siderophores. Here we investigated the utilization of these molecules by species of the Paracoccidioides genus, the causative agents of a systemic mycosis. It was demonstrated that iron starvation induces the expression of Paracoccidioides ortholog genes for siderophore biosynthesis and transport. Reversed-phase HPLC analysis revealed that the fungus produces and secretes coprogen B, which generates dimerumic acid as a breakdown product. Ferricrocin and ferrichrome C were detected in Paracoccidioides as the intracellular produced siderophores. Moreover, the fungus is also able to grow in presence of siderophores as the only iron sources, demonstrating that beyond producing, Paracoccidioides is also able to utilize siderophores for growth, including the xenosiderophore ferrioxamine. Exposure to exogenous ferrioxamine and dimerumic acid increased fungus survival during co-cultivation with macrophages indicating that these molecules play a role during host-pathogen interaction. Furthermore, cross-feeding experiments revealed that Paracoccidioides siderophores promotes growth of Aspergillus nidulans strain unable to produce these iron chelators. Together, these data denote that synthesis and utilization of siderophores is a mechanism used by Paracoccidioides to surpass iron limitation. As iron paucity is found within the host, siderophore production may be related to fungus pathogenicity.


M protein conserved region antibodies opsonise multiple strains of Streptococcus pyogenes with sequence variations in C-repeats.
The development of a group A streptococcal (GAS) vaccine has focused on the M protein, a major virulence factor. Antibodies against the amino terminal domain of the M protein are generally protective but only provide type-specific immunity. J14, a 29-mer peptide sequence which contains a conserved epitope from the C-repeat region of the M protein, offers the possibility of a vaccine which will elicit protective opsonic antibodies against multiple GAS strains. In this study we have shown that antibodies raised against J14 are capable of opsonising 37 GAS isolates representing different emm types derived from a region in which GAS infection is endemic. We also demonstrate that J14 antisera is capable of opsonising GAS isolates containing J14 homologues but not J14-specific sequences, further increasing the strain coverage of this vaccine candidate. Isolates with three C-repeats were opsonised more efficiently than isolates with two repeats. Opsonisation of a strain with only a single C-repeat was dramatically lower than other strains tested. The number of C-repeats present in the M protein of individual isolates therefore appears to be the critical factor in determining bactericidal capacity of J14 antisera. The reduced opsonic capacity of sera against this strain was shown to correlate with a reduced capacity to bind J14 antisera, as demonstrated by immunofluorescence microscopy and FACS analysis. In vivo challenge experiments also confirmed the protective efficacy of immunisation with J14 peptide.


In vivo infection of human T-cell leukemia virus type I in non-T cells.
Using three different procedures, immunomagnetic isolation, FACS and panning, each of the T4 cell, T8 cell, monocyte, and B cell population was fractionated from peripheral blood mononuclear cells (PBMC) obtained from 10 human T cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) cases, 3 adult T cell leukemia and lymphoma (ATLL) cases and 9 HTLV-I-infected healthy carriers. DNA from each fraction was then subjected to the quantitative polymerase chain reaction. Although T4 cells possessed the highest copy number of HTLV-I in general, we also detected a significant amount of HTLV-I provirus in T8 cells, monocytes, and B cells. To confirm virus infection of the non-T cell populations, especially the monocyte fraction, we performed further experiments and the following results were obtained: (1) HTLV-I tax RNA expression was confirmed simultaneously in the RNA of monocytes that were negative for T cell receptor beta chain (TCR beta) expression in vivo. (2) We cultured these monocytes for a short period of time and detected HTLV-I antigen expression in non-specific esterase-positive monocyte/macrophage cells. Our data indicate that HTLV-I has a broad host range in vivo and that monocytes or cells of monocyte lineage such as tissue macrophages might comprise a virus reservoir in vivo.


Cloning and expression of medaka cholesterol side chain cleavage cytochrome P450 during gonadal development.
Cholesterol side chain cleavage cytochrome P450 (P450scc, Cyp11a) is responsible for the first step in steroidogenesis, catalyzing the conversion of cholesterol to prognenolone. To investigate the differentiation of steroid-producing cells and the function of sex steroids during gonadal differentiation in the teleost fish, medaka (Oryzias latipes), we isolated the full length cDNA of medaka P450scc and analyzed the expression pattern of P450scc mRNA during gonadal development using in situ hybridization. At hatching, and just after the initiation of morphological sex differentiation, we did not detect any P450scc expression in both sexes. In male gonads, expression of P450scc was detected in the interstitial somatic cells 15 days after hatching following the formation of the seminiferous tubule precursor, and was maintained in the interstitial somatic cells throughout testicular development. In the female gonad, expression of P450scc was initially detected in interstitial somatic cells 5 days after hatching. Subsequently, the expression of P450scc was continuously detected in the interstitial somatic cells of the developing ovary. This expression pattern of P450scc differed from that of female specific steroidogenic enzyme P450arom. Both P450scc and P450arom expressing cells, only P450scc expressing cells, and only P450arom expressing cells were observed. Our results suggest that expression of steroidogenic enzymes is regulated by various mechanisms during ovarian development.


Clinical characteristics of severe supracondylar humerus fractures in children.
The safety of delayed surgical treatment of severe supracondylar elbow fractures in children remains debated. No large studies have evaluated complications of injury and surgery evaluating only type 3 fractures. Our aim was to review the results of our experience treating children with severe supracondylar elbow fractures at various time points after injury. All children treated operatively for supracondylar humerus fractures from 2004 to 2007 at a single pediatric trauma center were identified. A total of 1296 children had operative treatment, of which 872 had type 3 fractures. Clinical records were reviewed to identify time to surgery from presentation at our institution. Patients were grouped into 4 cohorts [<6 h (n=325), 6 to 12 h (n=224), 12 to 24 h (n=295), and >24 h (n=28)]. Emergency, operative, inpatient, and outpatient records were reviewed to determine morbidity at presentation as well as operative and postoperative complications. There was no difference in sex, age, or energy mechanism between children in the various time groups. An absent pulse was found in 54 children (6%) at presentation, of which only 5 ultimately required a vascular intervention. Nerve injury occurred in 105 patients (12%). Use of a medial entry pin was not associated with ulnar nerve injury. Increased time from presentation to surgery was not associated with increased morbidity from the injury or treatment complications. In contrast, there was a trend to steady decrease in morbidity and complication rates with increased time to surgery. This is the largest single-center study of severe supracondylar humerus fractures and describes rates of vascular compromise, nerve injury, infection, and other complications of these injuries. Most children with type 3 supracondylar humerus fractures can be treated safely in a delayed manner. Appropriate clinical judgment is imperative to optimize outcomes. Level III--retrospective comparative study.


Incorporating patch subspace model in Mumford-Shah type active contours.
In this paper, we propose a unified energy minimization model for segmentation of non-smooth image structures, e.g., textures, based on Mumford-Shah functional and linear patch model. We consider that image patches of a non-smooth image structure can be modeled by a patch subspace, and image patches of different non-smooth image structures belong to different patch subspaces, which leads to a computational framework for segmentation of non-smooth image structures. Motivated by the Mumford-Shah model, we show that this segmentation framework is equivalent to minimizing a piecewise linear patch reconstruction energy. We also prove that the error of segmentation is bounded by the error of the linear patch reconstruction, meaning that improving the linear patch reconstruction for each region leads to reduction of the segmentation error. In addition, we derive an algorithm for the linear patch reconstruction with proven global optimality and linear rate of convergence. The segmentation in our method is achieved by minimizing a single energy functional without requiring predefined features. Hence, compared with the previous methods that require predefined texture features, our method can be more suitable for handling general textures in unsupervised segmentation. As a by-product, our method also produces a dictionary of optimized orthonormal descriptors for each segmented region. We mainly evaluate our method on the Brodatz textures. The experiments validate our theoretical claims and show the clear superior performance of our methods over other related methods for segmentation of the textures.


CD8+ T cells cause disability and axon loss in a mouse model of multiple sclerosis.
The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis.


Genetic variation and haplotype structures of the glutathione S-transferase genes GSTA1 and GSTA2 in Japanese colorectal cancer patients.
Glutathione S-transferases (GSTs) play a vital role in the phase II biotransformation of many chemicals, including anticancer drugs. In this study, to elucidate the haplotype structures of the two closely related alpha-class genes GSTA1 and GSTA2, we screened for genetic variation in 214 Japanese colorectal cancer patients who received oxaliplatin-based chemotherapy. By direct resequencing of the 5'-flanking region, all the exons, and their flanking introns for 107 patients, 29 and 27 variants were identified in GSTA1 and GSTA2, respectively. The known functional single nucleotide polymorphisms (SNPs) -567T>G, -69C>T, and -52G>A in GSTA1*B were found at allele frequencies of 0.140. Of the four major GSTA2 allelic variants reported previously (GSTA2*A, *B, *C, and *E), only GSTA2*B (frequency = 0.154), *C (0.706), and *E (0.140) were detected. Following linkage disequilibrium analysis, haplotypes of both genes were separately estimated. Then, rapid genotyping methods for 7 and 6 SNPs tagging common haplotypes of GSTA1 and GSTA2, respectively, were developed using the single-base extension assay, and an additional 107 patients were genotyped. Finally, haplotype combinations of both genes were classified into 3 major types: GSTA1*A-GSTA2*C, GSTA1*A-GSTA2*B, and GSTA1*B-GSTA2*E. These findings will be useful in pharmacogenomic studies on xenobiotics including anticancer drugs.


Taming the Tongue: The Surgical Approach to Macroglossia.
While traditionally in the realm of otorhinolaryngology or oral maxillofacial surgery, conditions involving the tongue may also be managed by plastic surgeons. The authors present an unusual case of acquired macroglossia resulting from angiotensin-converting enzyme inhibitor-induced angioedema and review the literature to discuss its surgical management from a plastic surgery perspective. A 62-year-old female suffered severe airway obstruction, respiratory arrest, and anoxic brain injury from angioedema-associated macroglossia. After tracheostomy, the patient was managed nonsurgically, with bite wound care and medications to minimize angioedema to marginal effect. Ultimately, a partial glossectomy was planned. The edematous distal tongue was amputated and closed primarily. On postoperative day 2, she was successfully weaned off mechanical ventilation and no longer suffers trauma from tongue biting. The simple anterior tongue resection described in this paper was an appropriate approach for our patient. More research is needed to guide plastic surgeons in an optimal approach for clinical scenarios.


Ontogenetic differences in heterostylous plants and implications for development from a herkogamous ancestor.
Alternative ontogenetic pathways among heterostylous species of Rubiaceae may reflect differences in their evolutionary histories. In this study, measurements were taken at different developmental stages on a series of long-styled (LS) and short-styled (SS) buds of the heterostylous taxa Psychotria chiapensis, P. poeppigiana, and Bouvardia ternifolia (all Rubiaceae). Results indicated that modifications in growth rates of stamens relative to corollas in all three species led to differences in anther heights between LS and SS flowers. Distinct style heights for LS and SS flowers of P. chiapensis and P. poeppigiana originate in the earlier stages of bud development and are maintained as styles elongate at equal rates. This contrasts with B. ternifolia, which has differences in style heights resulting from unequal relative growth rates between floral morphs. The "approach herkogamous" floral morphology, defined by having stigmas positioned above anthers, has been proposed as a potential evolutionary precursor for heterostylous taxa. To examine this hypothesis, floral development of two species with approach herkogamous morphologies, Psychotria pittieri and P. brachiata, was compared to that of the three heterostylous taxa. Differences in the relative rates of style elongation for flowers of approach herkogamous versus heterostylous species predict additional steps in the original model for the evolution of heterostyly from an approach herkogamous ancestor. The diversity of heterostylous ontogenies found within Rubiaceae provides insight into potential evolutionary pathways for this sexual system in other angiosperm families.


Transcatheter Tricuspid Valve Intervention in Patients With Right Ventricular Dysfunction or Pulmonary Hypertension: Insights From the TriValve Registry.
Scarce data exist on patients with right ventricular dysfunction (RVD) or pulmonary hypertension (PH) undergoing transcatheter tricuspid valve intervention. This study aimed to determine the early and midterm outcomes and the factors associated with mortality in this group of patients. This subanalysis of the multicenter TriValve (Transcatheter Tricuspid Valve Therapies) registry included 300 patients with severe tricuspid regurgitation with RVD (n=244), PH (n=127), or both (n=71) undergoing transcatheter tricuspid valve intervention. RVD was defined as a tricuspid annular plane systolic excursion <17 mm, and PH as an estimated pulmonary artery systolic pressure ≥50 mm Hg. Mean age of the patients was 77±9 years (54% women). Procedural success was 80.7%, and 9 patients (3%) died during the hospitalization. At a median follow-up of 6 (interquartile range, 2-12) months, 54 patients (18%) died, and the independent associated factors were higher gamma-glutamyl transferase values at baseline (hazard ratio, 1.02 for each increase of 10 u/L [95% CI, 1.002-1.04]), poorer renal function defined as an estimated glomerular filtration rate <45 mL/min (hazard ratio, 2.3 [95% CI, 1.22-4.33]), and the lack of procedural success (hazard ratio, 2.11 [95% CI, 1.17-3.81]). The grade of RVD and the amount of PH at baseline were not found to be predictors of mortality. Most patients alive at follow-up improved their functional class (New York Heart Association I-II in 66% versus 7% at baseline, P<0.001). In patients with severe tricuspid regurgitation and RVD/PH, transcatheter tricuspid valve intervention was associated with high procedural success and a relatively low in-hospital mortality, along with significant improvements in functional status. However, about 1 out of 5 patients died after a median follow-up of 6 months, with hepatic congestion, renal dysfunction, and the lack of procedural success determining an increased risk. These results may improve the clinical evaluation of transcatheter tricuspid valve intervention candidates and would suggest a closer follow-up in those at increased risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03416166.


Heterozygosity loss at 22q and lack of INI1 gene mutation in gastrointestinal stromal tumor.
Gastrointestinal stromal tumor (GIST) is characterized by KIT or PDGFRA gene mutation. Although chromosomal losses of 22q are frequent in GIST, it is unclear which tumor suppressor genes might be inactivated in association with such losses. The INI1 gene, located at 22q11.23, is a tumor suppressor gene that is frequently altered in malignant rhabdoid tumor. To elucidate the hypothesis that the INI1 gene might be altered along with 22q loss in GIST, we examined the loss of heterozygosity (LOH) at 22q11.23, homozygous deletion and mutation of the INI1 gene, and its gene product expression as well as mutations of KIT and PDGFRA in 27 cases of GIST. Among the 27 informative cases, 19 (70.4%) showed LOH of at least one of the microsatellite markers on 22q11.23. None of the cases (0%) showed homozygous deletion or mutation of the INI1 gene. Immunohistochemically, the INI1 expression was focally reduced in 17/27 (63%) cases, and the INI1 protein level and INI1 mRNA level were each correlated with the presence of 22q11.23 LOH. Although the 22q11.23 LOH was more frequently present in high- than in low-grade tumors, INI1 expression level was not correlated with tumor grade, tumor size, proliferative activity and the expression levels of cyclin D1 and p16INK4a. KIT mutations were found in 18/27 (66.7%) GISTs; however, the KIT genotype was not correlated with the status of LOH at 22q11.23. The results suggest that 22q11.23 LOH is frequently present in GIST irrespective of KIT genotype and it might play a role in part of the development of GIST. However, the hemiallelic loss of INI1 gene causing reduced expression of INI1 protein probably does not have a major impact in the progression of GIST.


Prevalence of overweight misperception and weight control behaviors among normal weight adolescents in the United States.
Weight perceptions and weight control behaviors have been documented with underweight and overweight adolescents, yet limited information is available on normal weight adolescents. This study investigates the prevalence of overweight misperceptions and weight control behaviors among normal weight adolescents in the U.S. by sociodemographic and geographic characteristics. We examined data from the 2003 Youth Risk Behavior Survey (YRBS). A total of 9,714 normal weight U.S. high school students were included in this study. Outcome measures included self-reported height and weight measurements, overweight misperceptions, and weight control behaviors. Weighted prevalence estimates and odds ratios were computed. There were 16.2% of normal weight students who perceived themselves as overweight. Females (25.3%) were more likely to perceive themselves as overweight than males (6.7%) (p < 0.05). Misperceptions of overweight were highest among white (18.3%) and Hispanic students (15.2%) and lowest among black students (5.8%). Females (16.8%) outnumbered males (6.8%) in practicing at least one unhealthy weight control behavior (use of diet pills, laxatives, and fasting) in the past 30 days. The percentage of students who practiced at least one weight control behavior was similar by ethnicity. There were no significant differences in overweight misperception and weight control behaviors by grade level, geographic region, or metropolitan status. A significant portion of normal weight adolescents misperceive themselves as overweight and are engaging in unhealthy weight control behaviors. These data suggest that obesity prevention programs should address weight misperceptions and the harmful effects of unhealthy weight control methods even among normal weight adolescents.


Natural history and management of brainstem gliomas in adults. A retrospective Italian study.
Brainstem gliomas in adults are rare tumors, with heterogeneous clinical course; only a few studies in the MRI era describe the features in consistent groups of patients. In this retrospective study, we report clinical features at onset, imaging characteristics and subsequent course in a group of 34 adult patients with either histologically proven or clinico-radiologically diagnosed brainstem gliomas followed at two centers in Northern Italy. Of the patients 18 were male, 14 female, with a median age of 31. In 21 of the patients histology was obtained and in 20 it was informative (2 pilocytic astrocytoma, 9 low-grade astrocytoma, 8 anaplastic astrocytoma and 1 glioblastoma). Contrast enhancement at MRI was present in 14 patients. In all of the 9 patients who were investigated with MR spectroscopy, the Cho/NAA ratio was elevated at diagnosis. In 8 of the patients, an initial watch and wait policy was adopted, while 24 were treated shortly after diagnosis with either radiotherapy alone [4] or radiotherapy and chemotherapy [20] (mostly temozolomide). Only minor radiological responses were observed after treatments; in a significant proportion of patients (9 out of 15) clinical improvement during therapy occurred in the context of radiologically (MRI) stable disease. Grade III or IV myelotoxicity was observed in 6 patients. After a follow-up ranging from 9 to 180 months, all but 2 patients have progressed and 14 have died (12 for disease progression, 2 for pulmonary embolism). Median overall survival time was of 59 months. Investigation of putative prognostically relevant parameters showed that a short time between disease onset and diagnosis was related to a shorter survival. Compared with literature data, our study confirms the clinical and radiological heterogeneity of adult brainstem gliomas and underscores the need for multicenter trials in order to assess the efficacy of treatments in these tumors.


Management of pediatric urinary tract infections in the emergency department.
Urinary tract infection (UTI) is a common diagnosis in pediatric patients presenting to the emergency department. Although there are several evidence-based guidelines for UTI, they have small variations that can make the workup and management for UTI challenging. This issue reviews the current state of the literature and best practices for the diagnosis and management of UTI in children presenting to the emergency department, including criteria to help the clinician decide whether to test a patient's urine, the best method for urine testing based on the clinical scenario, and how to manage the patient based on the results of urine testing. Also discussed is the best antibiotic choice for specific patients, including the route of administration and duration.


Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes.
Extracellular vesicles with their molecular cargo can modulate target cell response and may affect the pathogenesis of diseases. The extracellular vesicles containing micro-RNAs (miRNAs), which are often studied as disease biomarkers, but rarely as mediators of the disease development. The role of extracellular vesicles derived miRNAs in type 1 diabetes is currently not well established. We observed a fraction of blood plasma extracellular vesicles positive for membrane proteins potentially associated with insulin-producing beta-cells and identified differentially expressed extracellular vesicles derived miRNAs in individuals with type 1 diabetes. These differentially expressed extracellular vesicles derived human miRNAs in participants with type 1 diabetes and participants with Langerhans islets beta-cells destruction showed the ability to activate TLR7/8 signaling cascade and increase activation as well as cytotoxicity of the effector blood immune cells with cytokine and chemokine release. Our results illustrate extracellular vesicles derived human miRNAs as modulators of the immune system in type 1 diabetes autoimmunity, providing potentially new insight into the pathogenesis of the disease, and novel molecular targets for intervention and type 1 diabetes prevention.


A confidence building exercise in data and identifiability: Modeling cancer chemotherapy as a case study.
Mathematical modeling has a long history in the field of cancer therapeutics, and there is increasing recognition that it can help uncover the mechanisms that underlie tumor response to treatment. However, making quantitative predictions with such models often requires parameter estimation from data, raising questions of parameter identifiability and estimability. Even in the case of structural (theoretical) identifiability, imperfect data and the resulting practical unidentifiability of model parameters can make it difficult to infer the desired information, and in some cases, to yield biologically correct inferences and predictions. Here, we examine parameter identifiability and estimability using a case study of two compartmental, ordinary differential equation models of cancer treatment with drugs that are cell cycle-specific (taxol) as well as non-specific (oxaliplatin). We proceed through model building, structural identifiability analysis, parameter estimation, practical identifiability analysis and its biological implications, as well as alternative data collection protocols and experimental designs that render the model identifiable. We use the differential algebra/input-output relationship approach for structural identifiability, and primarily the profile likelihood approach for practical identifiability. Despite the models being structurally identifiable, we show that without consideration of practical identifiability, incorrect cell cycle distributions can be inferred, that would result in suboptimal therapeutic choices. We illustrate the usefulness of estimating practically identifiable combinations (in addition to the more typically considered structurally identifiable combinations) in generating biologically meaningful insights. We also use simulated data to evaluate how the practical identifiability of the model would change under alternative experimental designs. These results highlight the importance of understanding the underlying mechanisms rather than purely using parsimony or information criteria/goodness-of-fit to decide model selection questions. The overall roadmap for identifiability testing laid out here can be used to help provide mechanistic insight into complex biological phenomena, reduce experimental costs, and optimize model-driven experimentation.