Nano-Bio Interactions of Extracellular Vesicles with Gold Nanoislands for Early Cancer Diagnosis.

Extracellular vesicles or exosomes are membrane encapsulated biological nanometric particles secreted virtually by all types of cells throughout the animal kingdom. They carry a cargo of active molecules to proximal and distal cells of the body as mechanism of physiological communication, to maintain natural homeostasis as well as pathological responses. Exosomes carry a tremendous potential for liquid biopsy and therapeutic applications. Thus, there is a global demand for simple and robust exosome isolation methods amenable to point-of-care diagnosis and quality control of therapeutic exosome manufacturing. This can be achieved by molecular profiling of the exosomes for use with specific sets of molecular-markers for diagnosis and quality control. Liquid biopsy is undoubtedly the most promising diagnosis process to advance "personalized medicine." Currently, liquid biopsy is based on circulating cancer cells, cell free-DNA, or exosomes. Exosomes potentially provide promise for early-stage diagnostic possibility; in order to facilitate superior diagnosis and isolation of exosomes, a novel platform is developed to detect and capture them, based on localized surface plasmon resonance (LSPR) of gold nanoislands, through strong affinity between exosomes and peptide called Venceremin or Vn96. Physical modeling, based on the characteristics of the gold nanoislands and the bioentities involved in the sensing, is also developed to determine the detection capability of the platform, which is optimized experimentally at each stage. Preliminary results and modeling present a relationship between the plasmonic shift and the concentration of exosomes and, essentially, indicate possibilities for label-free early diagnosis.

Chemical exchange in novel spirobicyclic zwitterionic Janovsky complexes using dynamic 1H NMR spectroscopy.

Highly coloured Janovsky complexes have been known for over 120 years, being used in many colourimetric analytical procedures. In this present study, two novel and stable nitrocyclohexadienyl spirobicyclic, zwitterionic Janovsky anionic hydantoin sigma-complexes, rac-1,3-diisopropyl-6-nitro-2,4-dioxo-1,3-diazaspiro[4.5]deca-6,9-dien-8-ylideneazinate, ammonium internal salt (1) and 1,3-diisopropyl-2,4-dioxo-1,3-diazaspiro[4.5]deca-6,9-dien-8-ylideneazinate, ammonium internal salt (2) have been prepared and characterised by NMR, electrospray ionization mass spectrometry (ESI-MS) and UV/visible methods. For the p-mononitro-substituted complex (2), we discovered chemical exchange behaviour using 1D saturation transfer and 2D exchange spectroscopy (EXSY) (1)H NMR techniques. The coalescence temperature was determined to be 62 degrees C in d(3)-acetonitrile. Analysis of these data provided a Gibbs free energy of activation, DeltaG double dagger, of + 67 kJ mole(-1), a rate constant, k, coalescence of 220 Hz and an equilibrium constant, K(eqm), of 0.98 as estimates of the exchange process in this solvent. Of the two mechanisms proposed for this fluxional behaviour, ring opening to a substituted benzene or proton exchange, a further theoretical modelling study of 1D (1)H NMR spectra was able to confirm that simple proton exchange between the two nitrogen sites of the hydantoin ring provided an accurate simulation of the observed experimental evidence. Interestingly, the o,p-dinitro-substituted complex (1) did not show any chemical exchange behaviour up to 150 degrees C in d(3)-acetonitrile (to 75 degrees C) and d(6)-dimethyl sulfoxide (DMSO). Molecular modelling at the MM2 level suggests that steric collisions of an N-acyl isopropyl substituent of the hydantoin ring with the ortho-nitro group of the spirofused cyclohexadienyl ring prevents the proposed proton exchange mechanism occurring in this case.

Expression of the 5-HT2A serotoninergic receptor in human placenta and choriocarcinoma cells: mitogenic implications of serotonin.

Serotonin (5-hydroxytryptamine, 5-HT) has diverse physiological functions and acts as a mitogen in a variety of cell types, including bovine placental cells. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Previous studies have reported the presence of 5-HT(2) binding sites in human placental trophoblastic cells, but this has never been confirmed at the molecular level. In this study, we demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the human choriocarcinoma cell lines JEG-3 and BeWo as well as in normal human placental tissue. DNA sequencing has confirmed that the 5-HT(2A) receptor present in these cell lines and tissues is identical to the human 5-HT(2A) receptor found in platelets and in the cerebral cortex. This receptor was localized by immunofluorescence on the plasma membrane, in JEG-3 and BeWo cells. Furthermore, MTT proliferation assays revealed a positive effect of 5-HT on the proliferation of JEG-3 and BeWo cells. These results suggest that 5-HT constitutes a potent mitogen for neoplastic placental cells.

Evaluation of subchronic toxicity of n-butyl acetate vapor.

The subchronic toxicity of n-butyl acetate (nBA), a common industrial solvent, was tested in rats in a 13-week inhalation study. Male and female Sprague-Dawley (SD) rats were exposed to concentrations of 0, 500, 1500 or 3000 ppm nBA for 6 h per day, 5 days per week for 13 consecutive weeks. Transient signs of sedation were observed only during exposure to the 1500 and 3000 ppm concentrations. Body weights for the 1500 and 3000 ppm groups were significantly reduced. Feed consumption values for the 1500 and 3000 ppm groups were significantly lower than the control group. Weights of the liver, kidneys and spleen were significantly lower for the 3000 ppm male group; testes and adrenal gland weights for the 1500 and 3000 ppm groups and the lung weight for the 3000 ppm male group were significantly higher than for the control group. Signs of irritation of the glandular stomach and necrosis in the non-glandular stomach were observed in 3000 ppm female rats. Degeneration of the olfactory epithelium along the dorsal medial meatus and ethmoturbinates of the nasal passages of some 1500 and all 3000 ppm rats was also seen. The severity was mild to moderate for the 3000 ppm group and minimal to mild for the 1500 ppm group. No effects were observed in the lungs of any group. The no-observed-effect level (NOEL) for this study is considered to be 500 ppm. The data presented here are relevant to the toxicity risk assessment of n-butanol due to the rapid hydrolysis of nBA in vivo.

The effect of nitrous oxide on laryngeal mask cuff pressure.

During general anesthesia with the laryngeal mask airway (LMA), a significant increase in cuff pressure due to diffusion of nitrous oxide through the cuff wall occurs. This descriptive clinical study was conducted in a university teaching hospital ambulatory surgical center with 100 patients (ASA physical status, I-III; age, 5 months to 76 years; weight, 5.8-146.3 kg) undergoing general anesthesia with an LMA. The airway pressure at which the LMA seal was broken (leak pressure) was determined immediately after the insertion of the LMA. The LMA leak pressure was determined by closing the circuit pop-off valve and recording with a stethoscope at the neck the pressure at which the gas was first heard to escape around the LMA. The LMA cuff pressure was determined by connecting the check valve of the LMA pilot balloon to a sphygmomanometer. The mean LMA cuff pressure increased 16 +/- 8.2 mm Hg (1- to 30-minute group), 38.11 +/- 15.87 mm Hg (31- to 60-minute group), 39.53 +/- 16.9 mm Hg (61- to 90-minute group), 42.63 +/- 20.36 mm Hg (91- to 120-minute group), and 44.25 +/- 14.03 mm Hg (120- to 350-minute group). This study demonstrated that there was a gradual increase in the cuff pressure well over a 3-hour period during nitrous oxide and oxygen anesthesia.

Controversial issues in outpatient anesthesia: adult and pediatric.

The 21st century will bring a new era of cost containment to the arena of ambulatory surgery force practitioners of anesthesia to reevaluate practice patterns. Along with the current increased interest in cost containment and optimal use of limited resources, growing concerns about patient outcome result in controversial issues in adult and pediatric outpatient anesthesia that must be addressed in the areas of preoperative evaluation, patient preparation and selection, laboratory screening, and practical discharge criteria. The future challenge for all practitioners is to provide high-quality anesthesia care at a reduced cost.

Neurotoxicity evaluation of rats after subchronic inhalation exposure to isobutanol.

The subchronic neurotoxic effects of isobutanol were studied by exposing Sprague-Dawley rats to isobutanol vapor concentrations of 0, 250, 1000, and 2500 ppm for 6 hrs/day, 5 days/wk, for 3 months. A comprehensive set of neurotoxicity tests (functional observational battery, motor activity, perfusion fixation neuropathology, and schedule-controlled operant behavior) including an assessment of complex behavior dependent on learning and memory was conducted. In addition, full histopathology and blood chemistry evaluations were conducted in order to assess any potential functional/behavioral effects in the context of other possible systemic toxicities. There were no morphological or behavioral effects indicative of a specific, persistent or progressive effect of isobutanol on the nervous system at exposure concentrations up to 2500 ppm. A slight decrease in response to external stimuli was observed during exposures at all concentrations. These effects are likely transient effects of acute exposure to isobutanol.

Evaluation of subchronic neurotoxicity of n-butyl acetate vapor.

n-Butyl acetate, a common industrial solvent, was selected by the US EPA as a chemical of concern for neurotoxicity as part of the Multisubstance Rule for the Testing of Neurotoxicity. The neurotoxic potential of n-butyl acetate was investigated in Sprague-Dawley rats using a functional observational battery, motor activity, neurohistopathology, and schedule-controlled operant behavior (SCOB) as indicators of neurotoxicity. Animals were exposed to concentrations of 0, 500, 1500, or 3000 ppm of n-butyl acetate for 6 hours per day for 65 exposures over 14 weeks. Functional observational battery and motor activity values for ad libitum-fed male and female rats were measured during Weeks -1, 4, 8, and 13. SCOB testing of food-restricted animals, using a multiple fixed ratio/fixed interval schedule, was conducted daily prior to each exposure to maintain the operant behavior; the data from Weeks -1, 4, 8, and 13 were evaluated for evidence of neurotoxicity. Transient signs of sedation and hypoactivity were observed only during exposure to the 1500 and 3000 ppm concentrations. The only signs of systemic toxicity were reduced body weights for the 3000 ppm ad libitum-fed groups and occasionally for the female 1500 ppm ad libitum-fed group. No evidence of neurotoxicity was seen during the functional observational battery examinations. Motor activity for the 3000 ppm male group was significantly (p < or = 0.05) higher than for the control group only during Week 4. No significant differences were observed among groups for Weeks 8 and 13. No significant differences in motor activity values were observed for female rats. No significant differences were seen in operant behavior at any test vapor concentration. Microscopic evaluations of sections from the brain, spinal cord (cervical and lumbar regions), dorsal and ventral spinal roots, dorsal root ganglia, sciatic nerve, and tibial nerve of animals in the control and 3000 ppm groups did not indicate any treatment-related effects. In conclusion, there was no evidence of cumulative neurotoxicity based on the functional observational battery, motor activity, neurohistopathology, and schedule-controlled operant behavior endpoints. The data presented here are relevant to the neurotoxicity risk assessment of n-butanol due to the rapid hydrolysis of n-butyl acetate in vivo.

Regional anesthesia: is it safer?

This article provides an overview of the current status of general anesthesia and regional anesthesia techniques including complications occurring after using these techniques. The advantages, disadvantages, mortality, and morbidity are described for these two techniques.

Comparison of four intraoperative warming devices.

Several methods of heat conservation and transfer have been suggested as aids to reducing heat loss during anesthesia. This study evaluated and compared the effectiveness of four warming and heat maintenance therapies. The efficacy of various heat conservation modalities was evaluated in 60 patients in five groups of 12 each, four experimental groups, and a control group. The study concluded that the Bair Hugger is more effective in maintaining normothermia during general anesthesia than is a reflective blanket, humidistat, or heated humidifier.

Midazolam: an induction agent for general anesthesia.

Midazolam is the first water soluble sedative widely used as an adjunct agent in general anesthesia. This 1,4-benzodiazepine derivative has been found to be a versatile agent, used as a premedicant, a hypnotic, an adjunct to intravenous conscious sedation, a long-term infused sedative agent, and more recently as an induction agent in selected situations. This report provides descriptive observations of midazolam used as an induction agent in 50 American Society of Anesthesiologists class I through III patients undergoing general anesthesia for elective or selected emergency surgeries. All inductions were preceded by 10 to 20 micrograms sufentanil. The use of sufentanil prior to the induction dose of midazolam facilitated a quicker onset of unconsciousness. Induction was smooth but gradual, and the course of anesthesia was otherwise satisfactory. Patients were alert and awake in the postanesthesia care unit. Recovery time was not prolonged due to somnolence or disorientation.

Panic attacks in the community. Social morbidity and health care utilization.

This article focuses on social morbidity and health care utilization in persons with panic attacks not meeting full diagnostic criteria for panic disorder. The findings are based on data from a random sample of over 18,000 adults drawn from five US communities. Panic attacks not meeting full criteria for panic disorder have a relatively high lifetime prevalence (3.6% of the adult population). Persons with panic attacks had impairment in perceived physical and emotional health, and in occupational and financial functioning, increased use of health care facilities, emergency departments, and psychoactive drugs. Persons with panic attacks were intermediate in severity between those with panic disorder and those with other psychiatric disorders. The findings could not be explained by comorbidity with other psychiatric disorders. We conclude that panic attacks have clinical significance and are associated with substantial morbidity.

Table-sag errors in CT treatment planning.

It is common practice to utilize CT scans in place of patient contours for computerized treatment planning. Our experience, in particular with pelvic patients, is that setting up the patient for a CT scan using landmarks from a radiation therapy simulator does not always produce accurate field margins. In general, the treatment field center as produced by the CT scan is superior to the center as defined by the simulator film. We have determined this problem to be caused by simulator table sag as compared to the CT. We offer suggestions to correct the problem.

Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey.

Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events.

Mainstreaming and postsecondary educational and employment status of a rubella cohort.

The postsecondary education and work status of 46 rubella deaf young adults was described and evaluated as an outcome of ethnicity, socioeconomic status, preschool attendance, early parent involvement, and degree of prior mainstreaming. With regard to postsecondary education attendance, 24 had two or more years, 11 had one year or less, and 11 had none. At time of interview, 19 were still attending school, 22 were working and five were neither working nor attending an educational program. Ethnic minority young adults were underrepresented in the group with two or more years of postsecondary education, and overrepresented in the group neither working nor in school at time of interview. Prior mainstreaming was a determinant of postsecondary education attendance over and above the effects of demographic and background characteristics. Implications of these findings are discussed.

Machine specific equivalent squares for two commonly employed blocked treatment fields.

In an attempt to find the most suitable method for determining the equivalent square for two commonly employed blocked field arrangements, a comparison of measured outputs was made for four different treatment machines. The machines varied by manufacturer, design, and energy. The fields in question were a midline-blocked field and a half-blocked field. The data obtained was used to streamline calculations made by technologists for the original treatment setting. It was further used to enhance the accuracy of computer-generated verification of the original setting. The authors recommend that each institution employing such fields consider obtaining similar data for their own treatment machines.