Frequency of electrode migration after cochlear implantation in the early postoperative period. What are associated risk factors?

OBJECTIVES: To estimate the prevalence of, and risk factors associated with electrode migration (EM) in cochlear implant (CI) recipients. DESIGN: Historical cohort study of all CIs performed between 1 January 2018 and 1 August 2021 in a single tertiary adult and paediatric CI centre in the UK. MAIN OUTCOME MEASURES: The primary aim is to determine the prevalence of electrode migration, comparing intraoperative surgeon report and examination of a routine plain radiograph performed 2 weeks after surgery. EM is defined as the detection of movement of two or more electrodes out of the cochlea from the time of surgery. Multivariate analysis was performed to investigate preoperative and intraoperative risk factors that might predispose to migration. RESULTS: Four hundred and sixty-five patients, having 516 distinct surgeries, with 628 implants were analysed. EM occurred following 11.5% of implant operations. Pre-existing cochlear abnormality was an independent associated risk factor for EM (OR: 3.40 ⟨1.20-9.62⟩ p = .021). Demographics, surgical technique, usage of a precurved electrode, CSF leak, surgeon seniority and intraoperative telemetry did not influence risk of migration. There were 5 implants (0.8%) which migrated later than 2 weeks, with a median date of imaging diagnosis (x-ray or CT scan) of 263 days ⟨IQR:198⟩, for which head injury was a common precipitating factor. There were differences in the risk of migration between different lateral wall electrodes. CONCLUSION: EM in the early postoperative period is a common occurrence and is more likely in implant recipients with obstructed or malformed cochleae.

The effect of administration of fenbendazole on the microbial hindgut population of the horse.

Anthelmintics are used as anti-worming agents. Although known to affect their target organisms, nothing has been published regarding their effect on other digestive tract organisms or on metabolites produced by them. The current work investigated effects of fenbendazole, a benzimidazole anthelmintic, on bacteria and ciliates in the equine digestive tract and on and their major metabolites. Animals receiving anthelmintic treatment had high faecal egg counts relative to controls. Analysis was performed over two weeks, with temporal differences detected in bacterial populations but with no other significant differences detected. This suggests fenbendazole has no detectable effect on organisms other than its targets. Moreover it does not appear to make a contribution to changing the resulting metabolome.

Multidimensional Sexual Perfectionism and Female Sexual Function: A Longitudinal Investigation.

Research on multidimensional sexual perfectionism differentiates four forms: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people's beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people's beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain, and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women's negative sexual self-concept and female sexual dysfunction.

Multidimensional sexual perfectionism.

Perfectionism is a multidimensional personality characteristic that can affect all areas of life. This article presents the first systematic investigation of multidimensional perfectionism in the domain of sexuality exploring the unique relationships that different forms of sexual perfectionism show with positive and negative aspects of sexuality. A sample of 272 university students (52 male, 220 female) completed measures of four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. In addition, they completed measures of sexual esteem, sexual self-efficacy, sexual optimism, sex life satisfaction (capturing positive aspects of sexuality) and sexual problem self-blame, sexual anxiety, sexual depression, and negative sexual perfectionism cognitions during sex (capturing negative aspects). Results showed unique patterns of relationships for the four forms of sexual perfectionism, suggesting that partner-prescribed and socially prescribed sexual perfectionism are maladaptive forms of sexual perfectionism associated with negative aspects of sexuality whereas self-oriented and partner-oriented sexual perfectionism emerged as ambivalent forms associated with positive and negative aspects.

Robust validation and performance comparison of immunogenicity assays assessing IgG and neutralizing antibodies to SARS-CoV-2.

To enable benchmarking of immunogenicity between candidate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there is a need for standardized, validated immunogenicity assays. In this article, we report the design and criteria used to validate immunogenicity assays and the outcome of the validation of serologic and functional assays for the evaluation of functional immune response and antibody titers in human serum. A quantitative cell-based microneutralization (MNT) assay, utilizing a reference standard, for detecting anti-SARS-CoV-2 spike protein-neutralizing antibodies in human serum and Meso Scale Discovery's multiplex electrochemiluminescence (MSD ECL) assay for immunoglobulin G (IgG) antibodies to SARS-CoV-2 spike, nucleocapsid, and receptor-binding domain (RBD) proteins were assessed for precision, accuracy, dilutional linearity, selectivity, and specificity using pooled human serum from coronavirus disease 2019 (COVID-19)-confirmed recovered donors. Both assays met prespecified acceptance criteria for precision, relative accuracy, dilutional linearity, selectivity, and specificity. Both assays demonstrated high specificity for the different SARS-CoV-2 antigens or virus tested, and no significant cross-reactivity with seasonal coronaviruses. An evaluation to compare the neutralizing activity in the MNT assay to the IgG measured using the MSD ECL assay showed a strong correlation between the presence of neutralizing activity and amount of antibodies against the spike and RBD proteins in sera from both convalescent and vaccinated individuals. Finally, the MNT assay was calibrated to the WHO reference standard to enable reporting of results in international units, thus facilitating comparison of immunogenicity data generated by different assays and/or laboratories. The MSD ECL assay has previously been calibrated. In conclusion, these validated assays for the evaluation of functional immune response and antibody titers following SARS-CoV-2 vaccination could provide a relatively simple standardized approach for accurately comparing immune responses to different vaccines and/or vaccination regimens.

Interventricular differences in myofilament function in experimental congestive heart failure.

This study was conducted to identify molecular mechanisms which explain interventricular differences in myofilament function in experimental congestive heart failure (CHF). CHF was induced in rats by chronic aortic banding or myocardial infarction for 32-36 weeks. Right and left ventricular (RV, LV) myocytes were mechanically isolated, triton-skinned, and attached to a force transducer and motor arm. Myofilament force-[Ca(2+)] relations assessed maximal Ca(2+)-saturated force (F (max)) and the [Ca(2+)] at 50% of F (max) (EC(50)). Myofilament protein phosphorylation was determined via ProQ diamond phospho-staining. Protein kinase C (PKC)-α expression/activation and site-specific phosphorylation of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were measured via immunoblotting. Relative to controls, failing RV myocytes displayed a ~45% decrease in F (max) with no change in EC(50), whereas failing LV myocytes displayed a ~45% decrease in F (max) and ~50% increase in EC(50). Failing LV myofilaments were less Ca(2+)-sensitive (37% increase in EC(50)) than failing RV myofilaments. Expression and activation of PKC-α was increased twofold in failing RV myocardium and relative to the RV, PKC-α was twofold higher in the failing LV, while PKC-ß expression was unchanged by CHF. PKC-α-dependent phosphorylation and PP1-mediated dephosphorylation of failing RV myofilaments increased EC(50) and increased F (max), respectively. Phosphorylation of cTnI and cTnT was greater in failing LV myofilaments than in failing RV myofilaments. RV myofilament function is depressed in experimental CHF in association with increased PKC-α signaling and myofilament protein phosphorylation. Furthermore, myofilament dysfunction is greater in the LV compared to the RV due in part to increased PKC-α activation and phosphorylation of cTnI and cTnT.

Race, psychosocial characteristics, and treatment outcomes among individuals undergoing treatment for cannabis use disorder: A latent profile analysis based on preferred method of using cannabis.

INTRODUCTION: There are a wide variety of methods for using combustible cannabis which may impact an individual's pattern of use as well as their response to cannabis use disorder (CUD) treatment. Previous research has noted racial/ethnic differences in cannabis users' preferred method of use. METHOD: The current study examined data from a randomized placebo-controlled trial of a pharmacological intervention for adults with CUD. Latent profile analysis classified participants (N = 302) based on their primary method of combustible cannabis use. RESULTS: A four profile solution emerged which identified participants who demonstrated 1) Primarily Joint (n = 50), 2) Primarily Blunt (n = 106), 3) Mixed MoU (n = 30), and 4) Primarily Pipe (i.e., pipe or bong; n = 116) use. Profiles were compared on socio-demographic characteristics and racial differences were found among the four latent profiles as well as differences in their level of use. Cannabis users with a preference for joints were more likely to be White as compared to other racial groups. In contrast, a greater proportion of participants with a preference for blunts were African American. The Primarily Joint profile was found to have the highest cannabis relapse rate at 1-month follow-up (94%) which was significantly greater than the Mixed MoU (74%, x2 = 5.06, p < .05) and Primarily Pipe (78%, x2 = 9.24, p < .01) profiles. Interestingly, there was no difference in 1-Month Follow-up cannabis relapse rates between the Primarily Joint and Blunt profiles (87%, x2 = 9.24, p > .05). CONCLUSIONS: Findings suggest that treatment-seeking individuals who primarily use joints or blunts may face unique challenges that may impact cannabis abstinence. Along with other cannabis-related characteristics, an individual's preferred method of use may represent an important factor to consider in the treatment of CUD.

Psychosocial intervention utilization and substance abuse treatment outcomes in a multisite sample of individuals who use opioids.

BACKGROUND: There are several relatively safe and effective FDA-approved medications for Opioid Use Disorder (OUD). Despite the existence of these medications, the rate of returning to opioid use after treatment is relatively high, underscoring the need for continued enhancement of treatments. Adjunctive psychosocial interventions paired with medication have been shown to improve OUD treatment outcomes. However, studies have yet to conclusively examine the distinct effects of the most widely utilized psychosocial treatment modalities. The current study will investigate the relationship between individual counseling, group therapy, and 12-Step participation and illicit opioid abstinence at the end of treatment, 1 and 3 months after treatment. METHOD: A secondary analysis was conducted with data from a sample of 570 individuals diagnosed with OUD who were recruited from eight substance abuse treatment centers in the United States. Participants were enrolled in a two-group randomized, controlled trial testing buprenorphine-naloxone versus extended-release naltrexone for OUD. A two-level hierarchical linear growth model was used to examine the effects of individual counseling, group therapy, and 12-Step participation on illicit opioid abstinence (urinanalyses) 1- and 3-months post-treatment. RESULTS: Hours of individual counseling and 12-Step participation significantly predicted abstinence at follow-up (p < .001, b = -0.59, 95% CI [0.42, 0.74]; p < .01, b = -0.05, 95% CI [0.92, 0.98]). There was a significant interaction between individual counseling and 12-Step participation (p < .01, b = -0.06, 95% CI [1.02, 1.10]). Additionally, participant age and employment status were significant predictors of illicit opioid abstinence (p < .01, b = -0.02, 95% CI [0.97, 0.99]; p < .01, b = -0.38, 95% CI [0.52, 0.90]). Hours of group therapy was not found to significantly predict illicit opioid abstinence. CONCLUSIONS: Findings suggest that greater levels of individual therapy and 12-Step participation may be beneficial for individuals receiving medication treatment for OUD.

Racial and gender inequities in the implementation of a cannabis criminal justice diversion program in a large and diverse metropolitan county of the USA.

BACKGROUND: Diversion programs are considered alternatives to the arrest and incarceration of non-violent drug offenders, including those found in possession of smaller amounts of cannabis in states with prohibitive laws. Despite the progressive nature of such programs, the inability to complete diversion program requirements can often result in greater involvement with the criminal justice system than traditional case adjudication. Few studies have evaluated racial group differences in cannabis diversion program completion. METHODS: The current study examined a sample of 8323 adult participants in Harris County, Texas' Marijuana Misdemeanor Diversion Program (MMDP) between March 2017 and July 2019. Gender, age, and race/ethnicity were examined as predictors of program completion and time to completion using Chi square, Kruskal Wallis tests, and Cox proportional hazard regression models. RESULTS: Both males and African Americans were over-represented (80 % and 50 %, respectively) among participants of Harris County's MMDP. African American (HR = 0.782, 95 % CI [.735-.832], p < .001) and Latino American MMDP participants (HR = .822, 95 % CI [.720-.937], p = .003) had significantly lower odds of MMDP completion and a longer interval to program completion as compared to non-Latino White participants. CONCLUSIONS: The current study identified racial/ethnic and gender disparities in a large county's cannabis diversion program. These findings may be related to law enforcement disparities which disproportionately target males and people of color. Findings may serve to inform the continued reform of the criminal justice system, particularly laws relating to cannabis.

A pilot randomized trial examining the feasibility and acceptability of a culturally tailored and adherence-enhancing intervention for Latino smokers in the U.S.

Latino smokers in the United States (US) are known to experience smoking cessation treatment disparities due to their under-utilization of services, limited access to health care, and poor smoking cessation treatment outcomes. A limited number of studies have focused on developing and testing smoking cessation treatments for Latino smokers in the US. The objectives of this study were to conduct a feasibility pilot randomized trial testing three smoking cessation interventions for Latinos. Twenty-five adult Latino smokers were randomized to one of three groups: Culturally-Tailored Smoking Cessation plus Adherence Enhancement (CT+AE), Culturally-Tailored Smoking Cessation (CTSC), and a Health Education (HE) control group. All participants received three counseling sessions along with nicotine replacement therapy (NRT). Data relating to intervention acceptability and NRT adherence were collected. Self-reported 7-day point prevalence smoking was collected at 3 and 6 month follow-up and biochemically verified with expired carbon monoxide testing. Overall, the interventions demonstrated high levels of feasibility and acceptability. Days of nicotine patch use were found to be higher in the CT+AE group (mean (M) = 81.3;standard deviation (SD) = 3.32) than the CTSC (M = 68.6;SD = 13.66) and HE (M = 64;SD = 17.70) groups. At 3-month follow-up, approximately 50% of the CT+AE group were smoking abstinent, 25% of the CTSC group, and 44% of the HE group. At 6-month follow-up, 37.5% of the CT+AE group were abstinent, 25% of the CTSC group, and 44.4% of the HE group. This study is the first to target Latino smokers in the US with a culturally-tailored intervention that addresses treatment adherence. Results support the preliminary feasibility and acceptability of the CT+AE intervention. Trial Registration: ClinicalTrials.gov NCT02596711.

A Decade of Experience With Continuous-Flow Left Ventricular Assist Devices.

The use of continuous-flow left ventricular assist devices (CF-LVADs) has revolutionized the landscape of mechanical circulatory support for patients with heart failure. Clinical trials are already testing the next generation of CF-LVADs. In this study, our objective was to review our long-term experience with the current generation of CF-LVADs, specifically, the HeartMate (HM) II (Thoratec Corp, Pleasanton, CA). In this single-center retrospective analysis, we evaluated the records of 278 consecutive patients who underwent a total of 302 HM II placements from June 2005 through June 2014. We excluded 11 patients from our final study group, who had previously undergone placement of a HM XVE that failed. We divided the remaining 267 patients into 3 equal groups of 89 patients each, by time period: group 1, June 2005 through May 2009; group 2, June 2009 through January 2012; and group 3, February 2012 through June 2014. To examine differences in survival between our 3 groups, we used time-to-event analysis, including the Kaplan-Meier method. To examine secondary outcomes (including stroke, hemolysis, gastrointestinal bleeding, pump thrombus, and transplant), we used one-way analysis of variance. For our final study group of 267 patients, the total follow-up time was 479.01 patient-years (median, 469 days). The mean age of patients was 57 years; 81.4% were male. In all, 209 (78.9%) patients underwent HM II placement as a bridge to transplant; 58 (21.1%), as destination therapy (DT). The overall survival rate was 94% at 30 days, 77% at 1 year, 65% at 2 years, 60% at 3 years, 50% at 4 years, and 48% at 5 years. In bridge to transplant patients, the survival rate was 78% at 1 year and 66% at 2 years; in DT patients, 70% and 60%. In group 1 patients, the survival rate was 94% at 30 days, 64% at 1 year, and 48% at 2 years; in group 2, 93%, 88%, and 76%; and in group 3, 94%, 77%, and 73% (P = 0.003). In the later years of our study period, from June 2009 onwards (ie, in groups 2 and 3), we noted a statistically significant increase in HM II placement as DT, a reduction of driveline infections, increasing pump exchange, increasing hemolysis, a reduced frequency of transplants, and an improved survival rate (as compared with the earlier group 1). The HM II has favorably influenced the outcomes of patients with end-stage heart failure, yet major complications still limit their survival. Improving compatibility between the pump and the individual host patient, enhancing anticoagulation strategies, and developing a totally implantable pump might further reduce complications thereby improving survival times and allowing CF-LVAD placement to be a true long-term alternative to a heart transplant.

Gastrointestinal Bleeding during Continuous-Flow Left Ventricular Assist Device Support is Associated with Lower Rates of Cardiac Transplantation.

Gastrointestinal bleeding (GIB) remains a significant problem after continuous-flow left ventricular assist device (CF-LVAD) implantation. We hypothesized that the subsequent need for blood transfusions in patients with GIB may reduce rates of cardiac transplantation. We performed a retrospective review of 232 patients implanted with the HeartMate II (HM II) CF-LVAD from June 2005 through May 2013 at our center to determine risk factors for GIB and assess its effect on cardiac transplantation. Over a total LVAD follow-up time of 364 person-years, 62 GIB episodes occurred in 49 patients (27%), for an event rate of 0.45 gastrointestinal bleeds/patient-year of LVAD support. Women made up 15% of our cohort, yet contributed 29% of the GIB (p = 0.06). Survival at 6 month, 1 year, and 2 years was not statistically different in patients who developed GIB and those who did not (77% vs 78%, 74% vs 71%, and 61% vs 54%, respectively). In transplant-eligible patients, GIB was associated with a 27% lower rate of cardiac transplantation (rate ratio 0.73, p < 0.05). Although the mechanism behind this finding is unclear, GIB appears to be linked to higher transfusion rates, which may cause the development of subsequent allosensitization.

Carpentier-Edwards aortic pericardial bioprosthetic valve as a valid control in preclinical in vivo ovine studies.

To progress into clinical practice, a bioprosthetic heart valve must first pass through the preclinical evaluation phase. The International Standards Organization (ISO) recommends implantation of concurrent controls in any evaluation of a new or modified heart valve. A total of 8 adult sheep underwent aortic valve replacement, receiving either the CE Perimount Magna 3000 aortic pericardial bioprosthetic valve or the CE Perimount RSR aortic pericardial bioprosthetic valve, Model 2800. We performed serial blood sampling, echocardiography, angiography and necropsy after euthanasia. All 8 sheep survived until the end of their study term. Our 2-dimensional echocardiographic analysis showed a mean pressure gradient of 37.4±6.0mmHg at 14 days and 37.0±5.9mmHg at 90 days; mean cardiac output was 10.0±2.8l/min at 14 days and 9.6±1.6l/min at 90 days. Angiography before euthanasia showed a mean aortic transvalvular gradient of 32.3±15.3mmHg. At euthanasia, we saw no evidence of calcification in any of the valves. In our study, we found that both models of the CE bioprosthetic heart valve we tested proved to be valid controls, in the aortic position, in sheep-with no evidence of calcification. Most important, the valves we tested had a few model-related problems, allowing a clear determination of their suitability for introduction into a clinical trial. Investigators now have additional insight into the safety of these 2 models of valves and perhaps will be able to reduce the number of controls implanted.

Stroke After Left Ventricular Assist Device Implantation: Outcomes in the Continuous-Flow Era.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used in patients with heart failure. To study the impact of stroke on clinical outcomes after continuous-flow (CF-) LVAD implantation, we evaluated our single-center experience. METHODS: From 2006 to 2013, we implanted the HeartMate II CF-LVAD in 230 patients. We used standard statistical methods to evaluate our results. RESULTS: Of our study group, 185 patients (80.4%) received the CF-LVAD as a bridge to transplantation. Strokes occurred in a total of 39 patients (17%), an incidence rate of 0.064 strokes per person-year: 19 (48.7%) were embolic, and 20 (51.3%) were hemorrhagic. The stroke-free rate at 6 months after HeartMate II implantation was 92.6%, at 12 months, 89.6%, and at 24 months, 86.1%. Baseline demographic characteristics did not differ significantly, except that stroke patients had a lower incidence of coronary artery disease (p = 0.004) and prior cardiac surgery (p = 0.001). We noted a trend toward an increased risk of stroke in patients with CF-LVAD-related infections (p = 0.053). The survival rate in stroke (versus stroke-free) patients at 6 months was 84.6% (versus 84.2%); at 12 months, 71.8% (versus 81.6%); and at 24 months, 53.9% (versus 74.7%; p = 0.0019). During a median follow-up time of 761 days, mortality risk in stroke patients was 2.01 times that of stroke-free patients (hazard ratio = 2.01; p = 0.004). CONCLUSIONS: Stroke while on CF-LVAD support was associated with significant mortality. To reduce the risk of stroke, it is essential to further elucidate risk factors, to optimize anticoagulation, and to further understand the impact of LVAD-related infections.

Left ventricular assist devices as a bridge to cardiac transplantation.

Heart failure remains a significant cause of morbidity and mortality, affecting over five million patients in the United States. Continuous-flow left ventricular assist devices (LVAD) have become the standard of care for patients with end stage heart failure. This review highlights the current state of LVAD as a bridge to transplant (BTT) in patients requiring mechanical circulatory support (MCS).

Gastrointestinal bleed after left ventricular assist device implantation: incidence, management, and prevention.

BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVADs) have become the standard of care for patients with end-stage heart failure (HF). While these devices have improved durability compared to earlier generation left ventricular assist devices (LVADs), increased frequency in some complications has been seen, including gastrointestinal bleeding (GIB), pump thrombosis and hemolysis. We discuss the incidence, management and prevention of GIB after CF-LVAD implantation. METHODS: We reviewed the current literature available on the incidence, management and prevention of GIB after CF-LVAD implantation with a focus on our experience at the University of Minnesota, with data on nearly 300 patients who received a CF-LVAD from 2005 to 2013. RESULTS: The incidence of GIB after CF-LVAD varies between 18-40% in numerous studies. At the University of Minnesota, out of 233 patients who underwent HeartMate II (HMII) implantation between 2005-2013, 60 GIB episodes occurred in 51 patients (22%), with an event rate of 0.17 gastrointestinal bleeds/patient-year of support. The etiology of GIB appears to be multifactorial. The main factors which have been identified include the need for chronic anticoagulation, acquired von Willebrand syndrome, platelet dysfunction and increased incidence of arteriovenous malformations due to chronic low pulse pressure. When managing an LVAD patient with GIB, a multi-disciplinary approach is needed. The main goals of treatment are evaluating the location and severity of the bleed, holding anti-coagulants and resuscitation to maintain stable hemodynamics. CONCLUSIONS: GIB is a complication with considerable morbidity. Future efforts to further understand the etiology of GIB and optimize anti-coagulation are needed to improve outcomes following CF-LVAD implantation.

Characterisation of gunshot residue from three ammunition types using suppressed anion exchange chromatography.

Gunshot residue (GSR) is commonly analysed in forensic casework using either scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) or gas chromatography-mass spectrometry (GC-MS). Relatively little work has been reported on the post-discharge GSR content of non-metallic inorganic or low molecular weight organic anions to distinguish between different ammunition types. The development of an analytical method using suppressed micro-bore anion exchange chromatography (IC) is presented for the analysis of GSR. A hydroxide gradient was optimised for the separation of 19 forensically relevant organic and inorganic anions in <23min and sensitivities of the order of 0.12-3.52ng of anion detected for all species were achieved. Along with an optimised extraction procedure, this method was applied to the analysis of post-ignition residues from three selected ammunition types. By profiling and comparing the anionic content in each ammunition residue, the possibility to distinguish between each type using their anionic profiles and absolute weight is presented. The potential for interference is also discussed with respect to sample types which are typically problematic in the analysis of GSR using SEM-EDX and GC-MS. To the best of our knowledge this represents the first study on the analysis of inorganic anions in GSR using suppressed ion chromatography.

Interleukin-1 beta secretion from cord blood mononuclear cells in vitro involves P2X 7 receptor activation.

The purinergic receptor P2X(7) is activated by extracellular adenosine 5'-triphosphate (ATP) and promotes the efficient release of interleukin-1 beta. The authors examine protein and molecular expression of the P2X(7) receptor and its ability to stimulate interleukin-1 beta release in cord blood mononuclear cells (CBMCs) from placentae of term nonlaboring and laboring women. They show both mRNA and protein (78 kDa) expression for the P2X( 7) receptor in CBMCs of parturient and nonparturient women. Costimulation of CBMCs in vitro with bacterial endotoxin and ATP resulted in significantly (P < .05) enhanced interleukin-1 beta release in laboring (54.17 +/- 24.78 pg/mL(-1); n = 8) compared with nonlaboring (13.60 +/- 3.20 pg/mL(-1); n = 7) deliveries. Release of interleukin-1 beta in both groups was blocked by preincubation with oxidized ATP, a P2X(7) receptor antagonist. The authors provide evidence for a novel inflammatory pathway in the release of interleukin-1 beta, which may be linked to the onset of labor.

Neural substrate for atrial fibrillation: implications for targeted parasympathetic blockade in the posterior left atrium.

The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M(2)) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M(2) receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 +/- 1, 3.2 +/- 2.5, and 0.17 +/- 0.3/cm(2) in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M(2) distribution was also most pronounced in the PLA (17.8 +/- 8.3, 14.3 +/- 7.3, and 14.5 +/- 8 M(2)-stained cells/cm(2) in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% (P < 0.001). We conclude that 1) P fibers and M(2) receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.