Analogous cortical reorganization accompanies entry into states of reduced consciousness during anesthesia and sleep.

Theories of consciousness suggest that brain mechanisms underlying transitions into and out of unconsciousness are conserved no matter the context or precipitating conditions. We compared signatures of these mechanisms using intracranial electroencephalography in neurosurgical patients during propofol anesthesia and overnight sleep and found strikingly similar reorganization of human cortical networks. We computed the "effective dimensionality" of the normalized resting state functional connectivity matrix to quantify network complexity. Effective dimensionality decreased during stages of reduced consciousness (anesthesia unresponsiveness, N2 and N3 sleep). These changes were not region-specific, suggesting global network reorganization. When connectivity data were embedded into a low-dimensional space in which proximity represents functional similarity, we observed greater distances between brain regions during stages of reduced consciousness, and individual recording sites became closer to their nearest neighbors. These changes corresponded to decreased differentiation and functional integration and correlated with decreases in effective dimensionality. This network reorganization constitutes a neural signature of states of reduced consciousness that is common to anesthesia and sleep. These results establish a framework for understanding the neural correlates of consciousness and for practical evaluation of loss and recovery of consciousness.

Predictive Validity of Anesthesiologists' Quality of Clinical Supervision and Nurse Anesthetists' Work Habits Assessed by Their Associations With Operating Room Times.

BACKGROUND: At all Joint Commission-accredited hospitals, the anesthesia department chair must report quantitative assessments of anesthesiologists' and nurse anesthetists' (CRNAs') clinical performance at least annually. Most metrics lack evidence of usefulness, cost-effectiveness, reliability, or validity. Earlier studies showed that anesthesiologists' clinical supervision quality and CRNAs' work habits have content, convergent, discriminant, and construct validity. We evaluated predictive validity by testing for (expected) small but statistically significant associations between higher quality of supervision (work habits) and reduced probabilities of cases taking longer than estimated. METHODS: Supervision quality of each anesthesiologist was evaluated daily by assigned trainees using the 9-item de Oliveira Filho scale. The work habits of each CRNA were evaluated daily by assigned anesthesiologists using a 6-item scale. Both are scored binary, 1 if all items are rated the maximum, 0 otherwise. From 40,718 supervision evaluations and 53,722 work habit evaluations over 8 fiscal years, 16 mixed-effects logistic regression models were estimated, with raters as fixed effects and ratees (anesthesiologists or CRNAs) as random effects. Empirical Bayes means in the logit scale were obtained for 561 anesthesiologist-years and 605 CRNA-years. The binary-dependent variable was whether the case took longer than estimated from the historical mean time for combinations of scheduled procedures and surgeons. From 264,060 cases, 8 mixed-effects logistic regression models were fitted, 1 per fiscal year, using ratees as random effects. Predictive validity was tested by pairing the 8 one-year analyses of clinical supervision, and the 8 one-year analyses of work habits, by ratee, with the 8 one-year analyses of whether OR time was longer than estimated. Bivariate errors in variable linear least squares linear regressions minimized total variances. RESULTS: Among anesthesiologists, 8.2% (46/561) had below-average supervision quality, and 17.7% (99/561), above-average. Among CRNAs, 6.3% (38/605) had below-average work habits, and 10.9% (66/605) above-average. Increases in the logits of the quality of clinical supervision were associated with decreases in the logits of the probabilities of cases taking longer than estimated, unitless slope = -0.0361 (SE, 0.0053), P < .00001. Increases in the logits of CRNAs' work habits were associated with decreases in the logits of probabilities of cases taking longer than estimated, slope = -0.0238 (SE, 0.0054), P < .00001. CONCLUSIONS: Predictive validity was confirmed, providing further evidence for using supervision and work habits scales for ongoing professional practice evaluations. Specifically, OR times were briefer when anesthesiologists supervised residents more closely, and when CRNAs had better work habits.

Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150 Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.

Synthesis, biological evaluations and computational studies of N-(3-(-2-(7-Chloroquinolin-2-yl)vinyl) benzylidene)anilines as fungal biofilm inhibitors.

In the present investigation, new chloroquinoline derivatives bearing vinyl benzylidene aniline substituents at 2nd position were synthesized and screed for biofilm inhibitory, antifungal and antibacterial activity. The result of biofilm inhibition of C. albicans suggested that compounds 5j (IC50 value = 51.2 µM) and 5a (IC50 value = 66.2 µM) possess promising antibiofilm inhibition when compared with the standard antifungal drug fluconazole (IC50 = 40.0 µM). Two compounds 5a (MIC = 94.2 µg/mL) and 5f (MIC = 98.8 µg/mL) also exhibited good antifungal activity comparable to standard drug fluconazole (MIC = 50.0 µg/mL). The antibacterial screening against four strains of bacteria viz. E. coli, P. aeruginosa, B. subtilis, and S. aureus suggested their potential antibacterial activity and especially all the compounds except 5g were found more active than the standard drug ciprofloxacin against B. subtilis. To further gain insights into the possible mechanism of these compounds in biofilm inhibition through the agglutinin like protein (Als), molecular docking and molecular dynamics simulation studies were carried out. Molecular modeling studies suggested the clear role in inhibition of this protein and the resulting biofilm inhibitory activity.

Electrocorticographic delineation of human auditory cortical fields based on effects of propofol anesthesia.

The functional organization of human auditory cortex remains incompletely characterized. While the posteromedial two thirds of Heschl's gyrus (HG) is generally considered to be part of core auditory cortex, additional subdivisions of HG remain speculative. To further delineate the hierarchical organization of human auditory cortex, we investigated regional heterogeneity in the modulation of auditory cortical responses under varying depths of anesthesia induced by propofol. Non-invasive studies have shown that propofol differentially affects auditory cortical activity, with a greater impact on non-core areas. Subjects were neurosurgical patients undergoing removal of intracranial electrodes placed to identify epileptic foci. Stimuli were 50Hz click trains, presented continuously during an awake baseline period, and subsequently, while propofol infusion was incrementally titrated to induce general anesthesia. Electrocorticographic recordings were made with depth electrodes implanted in HG and subdural grid electrodes implanted over superior temporal gyrus (STG). Depth of anesthesia was monitored using spectral entropy. Averaged evoked potentials (AEPs), frequency-following responses (FFRs) and high gamma (70-150Hz) event-related band power were used to characterize auditory cortical activity. Based on the changes in AEPs and FFRs during the induction of anesthesia, posteromedial HG could be divided into two subdivisions. In the most posteromedial aspect of the gyrus, the earliest AEP deflections were preserved and FFRs increased during induction. In contrast, the remainder of the posteromedial HG exhibited attenuation of both the AEP and the FFR. The anterolateral HG exhibited weaker activation characterized by broad, low-voltage AEPs and the absence of FFRs. Lateral STG exhibited limited activation by click trains, and FFRs there diminished during induction. Sustained high gamma activity was attenuated in the most posteromedial portion of HG, and was absent in all other regions. These differential patterns of auditory cortical activity during the induction of anesthesia may serve as useful physiological markers for field delineation. In this study, the posteromedial HG could be parcellated into at least two subdivisions. Preservation of the earliest AEP deflections and FFRs in the posteromedial HG likely reflects the persistence of feedforward synaptic activity generated by inputs from subcortical auditory pathways, including the medial geniculate nucleus.

Assessment of C-reactive Proteins, Cytokines, and Plasma Protein Levels in Hypertensive Patients with Apical Periodontitis.

INTRODUCTION: Chronic apical periodontitis (CAP) manifests mostly as periapical radiolucency. Various inflammatory mediators play a significant role in the pathogenesis of apical periodontitis. In acute inflammatory conditions, C-reactive proteins (CRP) and fibrinogen show a rise in their concentrations. In chronic diseases with high inflammatory components, an increased prevalence of hypertension has been observed. Hence, we assessed the association of CAP and plasma levels of various inflammatory markers (CRP, interleukin 6 [IL-6], and fibrinogen) in severely hypertensive patients. MATERIALS AND METHODS: This study was conducted in the conservative wing of the institute and included assessment of 250 hypertensive patients with apical periodontitis. With the help of periapical radiographs and clinical examination, the assessment of following parameters was done: Amount of teeth present, visible plaque index, periodontal pocket probing depth, clinical attachment level, bleeding on probing, presence/absence of carious lesions, which included assessment of caries in crown portion, in the root portion, and residual tooth roots (RR), presence of CAP from each patient; 8 mm of venous blood was collected in the morning for the assessment of plasma levels of IL-6, CRP, and fibrinogen levels. Immediate collection and processing of the samples were done in the hospital laboratory. All the results were analyzed by Statistical Package for the Social Sciences software. RESULTS: Out of 250, 155 patients were females. Mean plasma levels of CRP observed in our study were 0.8 mg/dL. Mean plasma levels of IL-6 and fibrinogen were found to be 3.3 and 337.1 mg/dL respectively. A significant correlation was observed while comparing mean body mass index (BMI), RR, and CAP in hypertensive patients. While comparing the mean plasma IL-6 levels, mean BMI, and CAP in the patients, significant results were obtained. Significant correlation was observed while comparing the mean BMI and CAP in hypertensive patients. CONCLUSION: Systemic levels of CRP, IL-6, and fibrinogen levels are influenced by the presence of CAP in hypertensive patients. CLINICAL SIGNIFICANCE: In hypertensive patients, CAP alters the systemic levels of various inflammatory markers.

Safety evaluation of flubendiamide and its metabolites on cabbage and persistence in soil in different agroclimatic zones of India.

Supervised field trials following good agricultural practices were conducted at the research farms of four agricultural universities located at four different agroclimatic zones of India to evaluate the persistence and dissipation of flubendiamide and its metabolite, des-iodo flubendiamide, on cabbage. Two spray applications of flubendiamide 480 SC of standard and double dose at the rate of 24 and 48 g a.i. ha(-1) were given to the crop at a 15-day interval, and the residues of flubendiamide 2 h after spray were found in the range of 0.107-0.33 and 0.20-0.49 mg kg(-1) at respective doses. Residue of des-iodo flubendiamide was not detected in any cabbage sample during study period. No residues were found in the soil samples collected from all treated fields after 15 days of application. On the basis of data generated under All India Network Project on Pesticide Residues, a preharvest interval (PHI) of 10 days has been recommended, and the flubendiamide 480 SC has been registered for its use on cabbage by Central Insecticide Board and Registration Committee, Ministry of Agriculture, Government of India. The maximum residue limit (MRL) of flubendiamide on cabbage has been fixed by the Ministry of Health and Family Welfare, Government of India, under Food Safety Standard Authority of India as 0.05 µg/g after its risk assessment.

Patient and Operational Factors Do Not Substantively Affect the Annual Departmental Quality of Anesthesiologists' Clinical Supervision and Nurse Anesthetists' Work Habits.

INTRODUCTION: Although safety climate, teamwork, and other non-technical skills in operating rooms probably influence clinical outcomes, direct associations have not been shown, at least partially due to sample size considerations. We report data from a retrospective cohort of anesthesia evaluations that can simplify the design of prospective observational studies in this area. Associations between non-technical skills in anesthesia, specifically anesthesiologists' quality of clinical supervision and nurse anesthetists' work habits, and patient and operational factors were examined. METHODS: Eight fiscal years of evaluations and surgical cases from one hospital were included. Clinical supervision by anesthesiologists was evaluated daily using a nine-item scale. Work habits of nurse anesthetists were evaluated daily using a six-item scale. The dependent variables for both groups of staff were binary, whether all items were given the maximum score or not. Associations were tested with patient and operational variables for the entire day. RESULTS: There were 40,718 evaluations of faculty anesthesiologists by trainees, 53,772 evaluations of nurse anesthetists by anesthesiologists, and 296,449 cases that raters and ratees started together. Cohen's d values were small (≤0.10) for all independent variables, suggesting a lack of any clinically meaningful association between patient and operational factors and evaluations given the maximum scores. For supervision quality, the day's count of orthopedic cases was a significant predictor of scores (P = 0.0011). However, the resulting absolute marginal change in the percentage of supervision scores equal to the maximum was only 0.8% (99% confidence interval: 0.2% to 1.4%), i.e., too small to be of clinical or managerial importance. Neurosurgical cases may have been a significant predictor of work habits (P = 0.0054). However, the resulting marginal change in the percentage of work habits scores equal to the maximum, an increase of 0.8% (99% confidence interval: 0.1% to 1.6%), which was again too small to be important. CONCLUSIONS: When evaluating the effect of assigning anesthesiologists and nurse anesthetists with different clinical performance quality on clinical outcomes, supervision quality and work habits scores may be included as independent variables without concern that their effects are confounded by association with the patient or case characteristics. Clinical supervision and work habits are measures of non-technical skills. Hence, these findings suggest that non-technical performance can be judged by observing the typical small sample size of cases. Then, associations can be tested with administrative data for a far greater number of patients because there is unlikely to be a confounding association between patient and case characteristics and the clinicians' non-technical performance.

Evaluation of Cytotoxic Effects of Purified Mercury in Human Gingival Fibroblasts-In vitro Study.

Background: Since the introduction of amalgam for tooth fillings, there have been concerns that mercury toxicity could pose unacceptable health risks. Rasa shastra is an ancient medical discipline that focuses on the utilization of metals and minerals for the treatment of diseases. Nevertheless, these minerals cannot be directly administered to the human body in their natural state due to their potential adverse effects. Hence, for medicinal purposes, these metals and minerals need to undergo purification (Shodhana) to eliminate impurities and modify their physical, chemical, and biological characteristics. Methodology: Human gingival fibroblasts (HGF) were exposed to commercially available mercury (CA-Hg) and ayurvedically purified mercury (AP-Hg) at concentrations of 6.25 µM, 12.5 µM, 25 µM and 50 µM. The unexposed HGF cultured in basal media was considered a control. All the samples were cultured for 24 hours and 48 hours, and the cytotoxicity was analyzed by MTT assay. Results: Cell viability between the control and experimental groups varied at 24 hours, however, the results were not statistically significant (p>0.05). At 48 hours, cell viability was higher in the AP-Hg group as compared to the CA-Hg group at the concentration of 6.25 µM, and the difference was statistically significant (p<0.05). The cell proliferation assay results demonstrated a statistically significant difference in the mean optical density values (p<0.05) between CA-Hg and AP-Hg at 12.50 µM, 25 µM, and 50, µM concentrations observed at 24 hours. At 48 hours, a statistically significant difference in the mean OD values (p<0.05) between CA-Hg and AP-Hg at all four concentrations was observed. Conclusion: AP-Hg at a concentration of 6.25 µM demonstrated higher cell viability at 48 hours. Further, the cell proliferation rate was also higher for AP-Hg at all concentrations at 24 and 48 hours. These results indicated a less cytotoxic effect of AP-Hg than CA-Hg in HGF and hence could be employed for dental amalgam preparations.

Implementation of a hotline ("S-T-I-C-K") to expedite management of occupational bloodborne pathogen exposures at an academic medical center: A Process Improvement Initiative.

Previously, blood and body fluid exposures were managed by a visit to the University Employee Health Clinic during normal business hours and the Emergency Department after hours. We implemented the "S-T-I-C-K" program where health care personnel were evaluated immediately after exposure by a nurse-driven 24/7 hotline. Increasing accessibility to care and a simplified process for exposure management led to a significant decrease in Emergency Department utilization and time between the exposure and receipt of post-exposure prophylaxis.

Compare the effcacy of two commercially available mouthrinses in reducing viable bacterial count in dental aerosol produced during ultrasonic scaling when used as a preprocedural rinse.

AIM: To evaluate and compare the effcacy of preprocedural mouthrinses (chlorhexidine digluconate and tea tree oil) in reducing microbial content of aerosol product during ultrasonic scaling procedures by viable bacterial count. SETTINGS AND DESIGN: It was a randomized single blind, placebo-controlled parallel group study. MATERIALS AND METHODS: Sixty subjects were randomly assigned to rinse 10 ml of any one of the mouthrinses (chlorhexidine digluconate or tea tree oil or distilled water). Ultrasonic scaling was done for a period of 10 minutes in presence of trypticase soy agar plates placed at standardized distance. Plates were then sent for microbiological evaluation for the aerosol produced. RESULTS: This study showed that all the antiseptic mouthwashes signifcantly reduced the bacterial colony forming units (CFUs) in aerosol samples. Chlorhexidine rinses were found to be superior to tea tree when used preprocedurally in reducing aerolized bacteria. CONCLUSION: This study advocates preprocedural dural rinsing with an effective antimicrobial mouthrinse during any dental treatment which generates aerosols, reduces the risk of cross-contamination with infectious agents in the dental operatory. CLINICAL SIGNIFICANCE: The aerolization of oral microbes occurring during dental procedures can potentially result in cross-contamination in the dental operatory and transmission of infectious agents to both dental professionals and patient. It is reasonable to assume therefore, that any stratagem for reducing the viable bacterial content of these aerosols could lower the risk of cross-contamination.

Postoperative Use of the Muscle Relaxants Baclofen and/or Cyclobenzaprine Associated With an Increased Risk of Delirium Following Lumbar Fusion.

STUDY DESIGN: Retrospective, single-center, cohort study. OBJECTIVE: Investigate whether the incidence of postoperative delirium in older adults undergoing spinal fusion surgery is associated with postoperative muscle relaxant administration. SUMMARY OF BACKGROUND DATA: Baclofen and cyclobenzaprine are muscle relaxants frequently used for pain management following spine surgery. Muscle relaxants are known to cause central nervous system side effects in the outpatient setting and are relatively contraindicated in individuals at high risk for delirium. However, there are no known studies investigating their side effects in the postoperative setting. METHODS: Patients over 65 years of age who underwent elective posterior lumbar fusion for degenerative spine disease were stratified into two treatment groups based on whether postoperative muscle relaxants were administered on postoperative day one as part of a multimodal analgesia regimen. Doubly robust inverse probability weighting with cox regression for time-dependent covariates was used to examine the association between postoperative muscle relaxant use and the risk of delirium while controlling for variation in baseline characteristics. RESULTS: The incidence of delirium was 17.6% in the 250 patients who received postoperative muscle relaxants compared with 7.9% in the 280 patients who did not receive muscle relaxants ( P=0.001 ). Multivariate analysis to control for variation in baseline characteristics between treatment groups found that patients who received muscle relaxants had a 2.00 (95% CI: 1.14-3.49) times higher risk of delirium compared with controls ( P=0.015 ). CONCLUSION: Postoperative use of muscle relaxants as part of a multimodal analgesia regimen was associated with an increased risk of delirium in older adults after lumber fusion surgery. Although muscle relaxants may be beneficial in select patients, they should be used with caution in individuals at high risk for postoperative delirium.

Failure to breathe persists without air hunger or alarm following amygdala seizures.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level-dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

Development of an analytical method for analysis of flubendiamide, des-iodo flubendiamide and study of their residue persistence in tomato and soil.

Flubendiamide is a new insecticide that has been found to give excellent control of lepidopterous pests of tomato. This study has been undertaken to develop an improved method for analysis of flubendiamide and its metabolite des-iodo flubendiamide and determine residue retention in tomato and soil. The analytical method developed involved extraction of flubendiamide and its metabolite des-iodo flubendiamide with acetonitrile, liquid-liquid partitioning into hexane-ethyl acetate mixture (6:4, v v⁻¹) and cleanup with activated neutral alumina. Finally the residues were dissolved in gradient high pressure liquid chromatography (HPLC) grade acetonitrile for analysis by HPLC. The mobile phase, acetonitrile-water at 60:40 (v v⁻¹) proportion and the wavelength of 235 nm gave maximum peak resolution. Using the above method and HPLC parameters described, nearly 100 % recovery of both insecticides were obtained. There was no matrix interference and the limit of quantification (LOQ) of the method was 0.01 mg kg⁻¹. Initial residue deposits of flubendiamide on field-treated tomato from treatments @ 48 and 96 g active ingredient hectare⁻¹ were 0.83 and 1.68 mg kg⁻¹, respectively. The residues of flubendiamide dissipated at the half-life of 3.9 and 4.4 days from treatments @ 48 and 96 g a.i. ha⁻¹, respectively and persisted for 15 days from both the treatments. Des-iodo flubendiamide was not detected in tomato fruits at any time during the study period. Residues of flubendiamide and des-iodo flubendiamide in soil from treatment @ 48 and 96 g a.i. ha⁻¹ were below detectable level (BDL, < 0.01 mg kg⁻¹) after 20 days. Flubendiamide completely dissipated from tomato within 20 days when the 480 SC formulation was applied at doses recommended for protection against lepidopterous pests.

Persistence and dissipation of fluopicolide in/on grape berries and soil under semi arid tropical climatic conditions of India.

Fluopicolide, a relatively new fungicide is used for control of downy mildew of grape. Persistence study of fluopicolide was carried out on grape berries following treatment of the combination product, fluopicolide 4.44% + fosetyl aluminium 66.7% (Profiler 71.14 WG) at the recommended and double the recommended dose of 2.5 and 5.0 kg ha⁻¹. Four treatment sprays were given at 15 day intervals, starting from 1 month after pruning of the vines. Residues of fluopicolide in grape berries were estimated on 0 (1 h), 1, 3, 5, 7, 10, 15, 20, 25, 30 day and at harvest (64 days after the last spray application). The initial residue deposits of fluopicolide on grape berries were 0.58 and 1.32 mg kg⁻¹ from treatment at the recommended and double dose, respectively. Dissipation of fluopicolide residues was a slow process. After 30 days of treatment, 0.068 and 0.204 mg kg⁻¹ of residues still remained in the berries from treatment at the recommended and double dose, respectively. Fluopicolide residues in grape berries dissipated with the half-life of 10.2 and 12.3 days. Residues in grape berries and soil at harvest were below the quantifiable limit of 0.01 mg kg⁻¹ from both the treatments.

Arousal State-Dependence of Interactions Between Short- and Long-Term Auditory Novelty Responses in Human Subjects.

In everyday life, predictable sensory stimuli are generally not ecologically informative. By contrast, novel or unexpected stimuli signal ecologically salient changes in the environment. This idea forms the basis of the predictive coding hypothesis: efficient sensory encoding minimizes neural activity associated with predictable backgrounds and emphasizes detection of changes in the environment. In real life, the brain must resolve multiple unexpected sensory events occurring over different time scales. The local/global deviant experimental paradigm examines auditory predictive coding over multiple time scales. For short-term novelty [hundreds of milliseconds; local deviance (LD)], sequences of identical sounds (/xxxxx/) are interspersed with sequences that contain deviants (/xxxxy/). Long-term novelty [several seconds; global deviance (GD)] is created using either (a) frequent /xxxxx/ and infrequent /xxxxy/ sequences, or (b) frequent /xxxxy/ and infrequent /xxxxx/ sequences. In scenario (a), there is both an LD and a GD effect (LDGD, "double surprise"). In (b), the global deviant is a local standard, i.e., sequence of identical sounds (LSGD). Cortical responses reflecting LD and GD originate in different brain areas, have a different time course, and are differentially sensitive to general anesthesia. Neural processes underlying LD and GD have been shown to interact, reflecting overlapping networks subserving the detection of novel auditory stimuli. This study examined these interactions using intracranial electroencephalography in neurosurgical patients. Subjects performed a GD target detection task before and during induction of anesthesia with propofol. Recordings were made from the auditory cortex, surrounding auditory-related and prefrontal cortex in awake, sedated, and unresponsive states. High gamma activity was used to measure the neural basis of local-by-global novelty interactions. Positive interaction was defined as a greater response to the double surprise LDGD condition compared to LSGD. Negative interaction was defined as a weaker response to LDGD. Positive interaction was more frequent than negative interaction and was primarily found in auditory cortex. Negative interaction typically occurred in prefrontal cortex and was more sensitive to general anesthesia. Temporo-parietal auditory-related areas exhibited both types of interaction. These interactions may have relevance in a clinical setting as biomarkers of conscious perception in the assessment of depth of anesthesia and disorders of consciousness.

Fate of fipronil and its metabolites in/on grape leaves, berries and soil under semi arid tropical climatic conditions.

Fate of fipronil and its major metabolites fipronil sulfide (MB 45950), fipronil-desulfinyl (MB 46513) and fipronil sulfone (MB 46136) were studied in/on grape leaves, berries and soil. As initial residue deposits on the leaves the major component was that of fipronil, while all the 3 metabolites were also present. Among metabolites residues of MB 46513 was highest followed by MB 46136 and MB 45950. In leaves fipronil degraded faster than its metabolites. The residues of fipronil in leaves degraded at the half-life of 9.6 and 18.3 days and that of total fipronil (sum of fipronil and its metabolites) at 13.6 and 20 days, from treatment at recommended and double the recommended dose, respectively. At the time of harvest in leaves, grape berries and soil residues of fipronil and all its metabolites were below the quantifiable limit of 0.01 mg kg(-1).

Persistence and dissipation of flubendiamide and des-iodo flubendiamide in cabbage (Brassica oleracea Linne) and soil.

Flubendiamide belongs to a novel class of insecticide which controls lepidopteran pest complex of cabbage such as diamondback moth, cabbage white butterfly, cluster caterpillar etc. Being a newly introduced insecticide no information is available on its residue persistence in cabbage. A study was undertaken to evaluate the residue persistence of flubendiamide in cabbage and soil following 2 applications of flubendiamide 480 SC at the recommended and double the recommended dose of 24 and 48 g a.i. ha(-1). Initial residue deposits of flubendiamide in cabbage were 0.33 and 0.49 mg kg(-1) respectively. The residues persisted for 10 days from the both the treatments and dissipated with the half-life of 3.9 and 4.45 days, respectively. Des-iodo flubendiamide, a metabolite of flubendiamide, was not detected in cabbage at any time during the study period. Soil sample collected from the treated field after 15 days was free from any residue of flubendiamide or its metabolite.

Patient safety in primary and outpatient health care.

Primary care services provide an entry point into the health system which directly impact's people well-being and their use of other health care resources. Patient safety has been recognised as an issue of global importance for the past 10 years. Unsafe primary and ambulatory care results in greater morbidity, higher healthcare usage and economic costs. According to data from World Health Organization (WHO), the risk of a patient dying from preventable medical accident while receiving health care is 1 in 300, which is much higher than risk of dying while travelling in an airplane. Unsafe medication practices and inaccurate and delayed diagnosis are the most common causes of patient harm which affects millions of patients globally. However, majority of the work has been focussed on hospital care and there is very less understanding of what can be done to improve patient safety in primary care. Provision of safe primary care is priority as every day millions of people use primary care services across the world. The present paper focuses on various aspects of patient safety, especially in the primary care settings and also provides some potential solutions in order to reduce patient harm as much as possible. Some important challenges regarding patient safety in India are also highlighted.

Transactivation of platelet-derived growth factor receptor alpha by the GTPase-deficient activated mutant of Galpha12.

The GTPase-deficient, activated mutant of Galpha12 (Galpha12Q229L, or Galpha12QL) induces neoplastic growth and oncogenic transformation of NIH 3T3 cells. Using microarray analysis, we have previously identified a role for platelet-derived growth factor receptor alpha (PDGFRalpha) in Galpha12-mediated cell growth (R. N. Kumar et al., Cell Biochem. Biophys. 41:63-73, 2004). In the present study, we report that Galpha12QL stimulates the functional expression of PDGFRalpha and demonstrate that the expression of PDGFRalpha by Galpha12QL is dependent on the small GTPase Rho. Our results indicate that it is cell type independent as the transient expression of Galpha12QL or the activation of Galpha12-coupled receptors stimulates the expression of PDGFRalpha in NIH 3T3 as well as in human astrocytoma 1321N1 cells. Furthermore, we demonstrate the presence of an autocrine loop involving PDGF-A and PDGFRalpha in Galpha12QL-transformed cells. Analysis of the functional consequences of the Galpha12-PDGFRalpha signaling axis indicates that Galpha12 stimulates the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway through PDGFR. In addition, we show that Galpha12QL stimulates the phosphorylation of forkhead transcription factor FKHRL1 via AKT in a PDGFRalpha- and PI3K-dependent manner. Since AKT promotes cell growth by blocking the transcription of antiproliferative genes through the inhibitory phosphorylation of forkhead transcription factors, our results describe for the first time a PDGFRalpha-dependent signaling pathway involving PI3K-AKT-FKHRL1, regulated by Galpha12QL in promoting cell growth. Consistent with this view, we demonstrate that the expression of a dominant negative mutant of PDGFRalpha attenuated Galpha12-mediated neoplastic transformation of NIH 3T3 cells.