Correction: Time-, space- and energy-resolved in situ characterization of catalysts by X-ray absorption spectroscopy.

Correction for 'Time-, space- and energy-resolved in situ characterization of catalysts by X-ray absorption spectroscopy' by Stefan Peters et al., Chem. Commun., 2023, 59, 12120-12123, https://doi.org/10.1039/D3CC03277A.

Defective COX1 expression in aging mice liver.

Mitochondrial defects are associated with aging processes and age-related diseases, including cardiovascular diseases, neurodegenerative diseases and cancer. In addition, some recent studies suggest mild mitochondrial dysfunctions appear to be associated with longer lifespans. In this context, liver tissue is considered to be largely resilient to aging and mitochondrial dysfunction. Yet, in recent years studies report dysregulation of mitochondrial function and nutrient sensing pathways in ageing livers. Therefore, we analyzed the effects of the aging process on mitochondrial gene expression in liver using wildtype C57BL/6N mice. In our analyses, we observed alteration in mitochondrial energy metabolism with age. To assess if defects in mitochondrial gene expression are linked to this decline, we applied a Nanopore sequencing based approach for mitochondrial transcriptomics. Our analyses show that a decrease of the Cox1 transcript correlates with reduced respiratory complex IV activity in older mice livers.

Time-, space- and energy-resolved in situ characterization of catalysts by X-ray absorption spectroscopy.

A setup for dispersive X-ray absorption spectroscopy (XAS) with spatial, temporal and energy resolution is presented. Through investigation of a Mo/HZSM-5 catalyst during the dehydroaromatization of methane we observed a reduction gradient along the packed bed. Our new method represents an unprecedented addition to the analytical toolbox for in situ characterizations.

Role of Mitochondrial Nucleic Acid Sensing Pathways in Health and Patho-Physiology.

Mitochondria, in symbiosis with the host cell, carry out a wide variety of functions from generating energy, regulating the metabolic processes, cell death to inflammation. The most prominent function of mitochondria relies on the oxidative phosphorylation (OXPHOS) system. OXPHOS heavily influences the mitochondrial-nuclear communication through a plethora of interconnected signaling pathways. Additionally, owing to the bacterial ancestry, mitochondria also harbor a large number of Damage Associated Molecular Patterns (DAMPs). These molecules relay the information about the state of the mitochondrial health and dysfunction to the innate immune system. Consequently, depending on the intracellular or extracellular nature of detection, different inflammatory pathways are elicited. One group of DAMPs, the mitochondrial nucleic acids, hijack the antiviral DNA or RNA sensing mechanisms such as the cGAS/STING and RIG-1/MAVS pathways. A pro-inflammatory response is invoked by these signals predominantly through type I interferon (T1-IFN) cytokines. This affects a wide range of organ systems which exhibit clinical presentations of auto-immune disorders. Interestingly, tumor cells too, have devised ingenious ways to use the mitochondrial DNA mediated cGAS-STING-IRF3 response to promote neoplastic transformations and develop tumor micro-environments. Thus, mitochondrial nucleic acid-sensing pathways are fundamental in understanding the source and nature of disease initiation and development. Apart from the pathological interest, recent studies also attempt to delineate the structural considerations for the release of nucleic acids across the mitochondrial membranes. Hence, this review presents a comprehensive overview of the different aspects of mitochondrial nucleic acid-sensing. It attempts to summarize the nature of the molecular patterns involved, their release and recognition in the cytoplasm and signaling. Finally, a major emphasis is given to elaborate the resulting patho-physiologies.

Designing a non-inferiority study in kidney transplantation: a case study.

In organ transplantation, placebo-controlled clinical trials are not possible for ethical reasons, and hence non-inferiority trials are used to evaluate new drugs. Patients with a transplanted kidney typically receive three to four immunosuppressant drugs to prevent organ rejection. In the described case of a non-inferiority trial for one of these immunosuppressants, the dose is changed, and another is replaced by an investigational drug. This test regimen is compared with the active control regimen. Justification for the non-inferiority margin is challenging as the putative placebo has never been studied in a clinical trial. We propose the use of a random-effect meta-regression, where each immunosuppressant component of the regimen enters as a covariate. This allows us to make inference on the difference between the putative placebo and the active control. From this, various methods can then be used to derive the non-inferiority margin. A hybrid of the 95/95 and synthesis approach is suggested. Data from 51 trials with a total of 17,002 patients were used in the meta-regression. Our approach was motivated by a recent large confirmatory trial in kidney transplantation. The results and the methodological documents of this evaluation were submitted to the Food and Drug Administration. The Food and Drug Administration accepted our proposed non-inferiority margin and our rationale.

The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment.

The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that RAGE functions as an endothelial adhesion receptor promoting leukocyte recruitment. In an animal model of thioglycollate-induced acute peritonitis, leukocyte recruitment was significantly impaired in RAGE-deficient mice as opposed to wild-type mice. In diabetic wild-type mice we observed enhanced leukocyte recruitment to the inflamed peritoneum as compared with nondiabetic wild-type mice; this phenomenon was attributed to RAGE as it was abrogated in the presence of soluble RAGE and was absent in diabetic RAGE-deficient mice. In vitro, RAGE-dependent leukocyte adhesion to endothelial cells was mediated by a direct interaction of RAGE with the beta2-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with beta1-integrins. The RAGE-Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein. These results were corroborated by analysis of cells transfected with different heterodimeric beta2-integrins, by using RAGE-transfected cells, and by using purified proteins. The RAGE-Mac-1 interaction defines a novel pathway of leukocyte recruitment relevant in inflammatory disorders associated with increased RAGE expression, such as in diabetes, and could provide the basis for the development of novel therapeutic applications.

Marked differences in the prevalence of chloroquine resistance between urban and rural communities in Burkina Faso.

BACKGROUND: Chloroquine (CQ) resistance has reached high levels in Africa in recent years. Little is known about variations of resistance between urban and rural areas. OBJECTIVES: To compare the rates of in vivo resistance to CQ and the prevalences of the main molecular marker for CQ resistance among young children from urban and rural areas in Burkina Faso. METHODS: The current analysis used the frame of a randomized controlled trial (ISRCTN27290841) on the combination CQ-methylene blue (MB) (n=177) compared to CQ alone (n=45) in young children with uncomplicated malaria. We examined clinical and parasitological failure rates as well as the prevalence of the Plasmodium falciparum chloroquine resistance transporter gene (pfcrt) T76 mutation. RESULTS: Clinical and parasitological failure rates of CQ-MB differed significantly between urban (70%) and rural areas (29%, p<0.0001). Likewise, CQ failure rates were higher in the urban setting. Matching this pattern, pfcrt T76 was more frequently seen among parasite strains from urban areas (81%) when compared to rural ones (64%, p=0.01). In the presence of parasites exhibiting pfcrt T76, the odds of overall clinical failure were increased to 2.6-fold ([1.33, 5.16], p(LR)=0.005). CQ was detected at baseline in 21% and 2% of children from the urban and the rural study area, respectively (p(Chi)=0.002). CONCLUSION: Even within circumscribed geographical areas, CQ efficacy can vary dramatically. The differences in the prevalence of pfcrt T76 and in CQ failure rates are probably explained by a higher drug pressure in the urban area compared to the rural study area. This finding has important implications for national malaria policies.

Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.

BACKGROUND AND PURPOSE: Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. METHODS: DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. RESULTS: A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23). CONCLUSIONS: DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

Acupuncture and knee osteoarthritis: a three-armed randomized trial.

BACKGROUND: Despite the popularity of acupuncture, evidence of its efficacy for reducing pain remains equivocal. OBJECTIVE: To assess the efficacy and safety of traditional Chinese acupuncture (TCA) compared with sham acupuncture (needling at defined nonacupuncture points) and conservative therapy in patients with chronic pain due to osteoarthritis of the knee. DESIGN: Randomized, controlled trial. SETTING: 315 primary care practices staffed by 320 practitioners with at least 2 years' experience in acupuncture. PATIENTS: 1007 patients who had had chronic pain for at least 6 months due to osteoarthritis of the knee (American College of Rheumatology [ACR] criteria and Kellgren-Lawrence score of 2 or 3). INTERVENTIONS: Up to 6 physiotherapy sessions and as-needed anti-inflammatory drugs plus 10 sessions of TCA, 10 sessions of sham acupuncture, or 10 physician visits within 6 weeks. Patients could request up to 5 additional sessions or visits if the initial treatment was viewed as being partially successful. MEASUREMENTS: Success rate, as defined by at least 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 weeks. Additional end points were WOMAC score and global patient assessment. RESULTS: Success rates were 53.1% for TCA, 51.0% for sham acupuncture, and 29.1% for conservative therapy. Acupuncture groups had higher success rates than conservative therapy groups (relative risk for TCA compared with conservative therapy, 1.75 [95% CI, 1.43 to 2.13]; relative risk for sham acupuncture compared with conservative therapy, 1.73 [CI, 1.42 to 2.11]). There was no difference between TCA and sham acupuncture (relative risk, 1.01 [CI, 0.87 to 1.17]). LIMITATIONS: There was no blinding between acupuncture and traditional therapy and no monitoring of acupuncture compliance with study protocol. In general, practitioner-patient contacts were less intense in the conservative therapy group than in the TCA and sham acupuncture groups. CONCLUSIONS: Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.

Ultrasound measurements of the distance between acupuncture needle tip at P6 and the median nerve.

BACKGROUND: Pericard 6 (P6) is one of the most frequently used acupuncture points, especially in preventing nausea and vomiting. At this point, the median nerve is located very superficially. OBJECTIVES: To investigate the distance between the needle tip and the median nerve during acupuncture at P6, we conducted a prospective observational ultrasound (US) imaging study. We tested the hypothesis that de qi (a sensation that is typical of acupuncture needling) is evoked when the needle comes into contact with the epineural tissue and thereby prevents nerve penetration. SETTINGS/LOCATION: The outpatient pain clinic of the Medical University of Vienna, Austria. SUBJECTS: Fifty (50) patients receiving acupuncture treatment including P6 bilaterally. INTERVENTIONS: Patients were examined at both forearms using US (a 10-MHz linear transducer) after insertion of the needle at P6. OUTCOME MEASURES: The distance between the needle tip and the median nerve, the number of nerve contacts and nerve penetrations, as well as the number of successfully elicited de qi sensations were recorded. RESULTS: Complete data could be obtained from 97 cases. The mean distance from the needle tip to the nerve was 1.8 mm (standard deviation 2.2; range 0-11.3). Nerve contacts were recorded in 52 cases, in 14 of which the nerve was penetrated by the needle. De qi was elicited in 85 cases. We found no association between the number of nerve contacts and de qi. The 1-week follow-up showed no complications or neurologic problems. CONCLUSIONS: This is the first investigation demonstrating the relationship between acupuncture needle placement and adjacent neural structures using US technology. The rate of median nerve penetrations by the acupuncture needle at P6 was surprisingly high, but these seemed to carry no risk of neurologic sequelae. De qi at P6 does not depend on median nerve contact, nor does it prevent median nerve penetration.

Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine.

The development of safe, effective and affordable drug combinations against malaria in Africa is a public health priority. Methylene blue (MB) has a similar mode of action as chloroquine (CQ) and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study on the combination MB-CQ was performed in 435 young children with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50% clinical failure rate in this area in 2003). Three serious adverse events (SAE) occurred of which one was probably attributable to the study medication. In the per protocol safety analysis, there were no dose specific effects. The overall clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%, 14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have efficacy against malaria, but the combination of CQ-MB is clearly not effective in the treatment of malaria in Africa.

Designing an acupuncture study: II. The nationwide, randomized, controlled German acupuncture trials on low-back pain and gonarthrosis.

BACKGROUND: In the nationwide German Acupuncture Trials (GERAC), verum acupuncture, mirroring the Traditional Chinese Medicine (TCM) acupuncture style, was tested against sham acupuncture and guideline standard therapy for the entities classified in the West as chronic low back pain (LBP) and gonarthrosis (GON). OBJECTIVE: The objective was to develop broadly consensual acupuncture and control protocols for the treatment of LBP and GON in the GERAC trials. METHODOLOGY: Extensive literature study and consultation with acupuncture experts were consulted. Personal interviews, both free and structured, e-mail discussions, and phone conferences were used as well. RESULTS: Broadly consensual acupuncture protocols for LBP and GON for verum and invasive sham acupuncture were developed. They included semistandardized point combinations with clearly described point selection rules based on TCM acupuncture diagnosis. A procedure was developed to help ensure homogenous treatment quality in a large multicenter trial. CONCLUSIONS: With 1162 randomized patients for LBP and 1039 patients for GON, the GERAC study design allowed acupuncture to be tested in a naturalistic environment. The rigorous study design and large number of physician investigators guaranteed a high external validity for the results. The results will help determine the significance of Chinese acupuncture in the context of Western medicine for the treatment of LBP and GON.

Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841].

BACKGROUND: Safe, effective and affordable drug combinations against falciparum malaria are urgently needed for the poor populations in malaria endemic countries. Methylene blue (MB) combined with chloroquine (CQ) has been considered as one promising new regimen. OBJECTIVES: The primary objective of this study was to evaluate the safety of CQ-MB in African children with uncomplicated falciparum malaria. Secondary objectives were to assess the efficacy and the acceptance of CQ-MB in a rural population of West Africa. METHODS: In this hospital-based randomized controlled trial, 226 children (6-59 months) with uncomplicated falciparum malaria were treated in Burkina Faso. The children were 4:1 randomized to CQ-MB (n = 181; 25 mg/kg CQ and 12 mg/kg MB over three days) or CQ (n = 45; 25 mg/kg over three days) respectively. The primary outcome was the incidence of severe haemolysis or other serious adverse events (SAEs). Efficacy outcomes were defined according to the WHO 2003 classification system. Patients were hospitalized for four days and followed up until day 14. RESULTS: No differences in the incidence of SAEs and other adverse events were observed between children treated with CQ-MB (including 24 cases of G6PD deficiency) compared to children treated with CQ. There was no case of severe haemolysis and also no significant difference in mean haemoglobin between study groups. Treatment failure rates were 53.7% (95% CI [37.4%; 69.3%]) in the CQ group compared to 44.0% (95% CI [36.3%; 51.9%]) in the CQ-MB group. CONCLUSION: MB is safe for the treatment of uncomplicated falciparum malaria, even in G6PD deficient African children. However, the efficacy of the CQ-MB combination has not been sufficient at the MB dose used in this study. Future studies need to assess the efficacy of MB at higher doses and in combination with appropriate partner drugs.

Comparison of efavirenz and nevirapine in HIV-infected patients (NEEF Cohort).

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) and nevirapine (NVP) taken in combination with nucleoside reverse transcriptase inhibitors (NRTIs) have both shown to be just as highly effective as protease inhibitors (PIs) in reducing viral load in patients infected with HIV. Our study compares the performance of these two NNRTIs with each other. This was a non-randomized, prospective, two-arm, multi-centre trial. We evaluated all patients with an EFV- or NVP-containing antiretroviral regimen. The primary endpoint was the difference in success rates defined as a viral load of

Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes.

OBJECTIVE: To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications. RESEARCH DESIGN AND METHODS: The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases. RESULTS: No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P = 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19-0.61]; P = 0.0002); no association with diabetic nephropathy was found. CONCLUSIONS: Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes.

Turkevich in New Robes: Key Questions Answered for the Most Common Gold Nanoparticle Synthesis.

This contribution provides a comprehensive mechanistic picture of the gold nanoparticle synthesis by citrate reduction of HAuCl4, known as Turkevich method, by addressing five key questions. The synthesis leads to monodisperse final particles as a result of a seed-mediated growth mechanism. In the initial phase of the synthesis, seed particles are formed onto which the residual gold is distributed during the course of reaction. It is shown that this mechanism is a fortunate coincidence created by a favorable interplay of several chemical and physicochemical processes which initiate but also terminate the formation of seed particles and prevent the formation of further particles at later stages of reaction. Since no further particles are formed after seed particle formation, the number of seeds defines the final total particle number and therefore the final size. The gained understanding allows illustrating the influence of reaction conditions on the growth process and thus the final size distribution.

Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses.

BACKGROUND: The aim of this study was to compare the validity of the Hospital Anxiety and Depression Scale (HADS), the WHO (five) Well Being Index (WBI-5), the Patient Health Questionnaire (PHQ), and physicians' recognition of depressive disorders, and to recommend specific cut-off points for clinical decision making. METHODS: A total of 501 outpatients completed each of the three depression screening questionnaires and received the Structured Clinical Interview for DSM-IV (SCID) as the criterion standard. In addition, treating physicians were asked to give their psychiatric diagnoses. Criterion validity and Receiver Operating Characteristics (ROC) were determined. Areas under the curves (AUCs) were compared statistically. RESULTS: All depression scales showed excellent internal consistencies (Cronbach's alpha: 0.85-0.90). For 'major depressive disorder', the operating characteristics of the PHQ were significantly superior to both the HADS and the WBI-5. For 'any depressive disorder', the PHQ showed again the best operating characteristics but the overall difference did not reach statistical significance at the 5% level. Cut-off points that can be recommended for the screening of 'major depressive disorder' had sensitivities of 98% (PHQ), 94% (WBI-5), and 85% (HADS). Corresponding specificities were 80% (PHQ), 78% (WBI-5), and 76% (HADS). In contrast, physicians' recognition of 'major depressive disorder' was poor (sensitivity, 40%; specificity, 87%). LIMITATIONS: Our sample may not be representative of medical outpatients, but sensitivity and specificity are independent of disorder prevalence. CONCLUSIONS: All three questionnaires performed well in depression screening, but significant differences in criterion validity existed. These results may be helpful in the selection of questionnaires and cut-off points.

Detecting panic disorder in medical and psychosomatic outpatients: comparative validation of the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire, a screening question, and physicians' diagnosis.

OBJECTIVES: To compare the validity of detecting panic disorder using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), a screening question, and physicians' diagnosis, and to test whether modified evaluation algorithms improve the operating characteristics of these questionnaires. Additionally, patient and physician acceptability of the screening questionnaires was investigated. METHODS: The total sample of 499 patients comprised 348 medical outpatients and 151 psychosomatic outpatients. The Structured Clinical Interview for DSM-IV (SCID) was the criterion standard for the presence of a panic disorder. Sensitivity, specificity, predictive values, and overall accuracy were compared for the different measures. The conditional test characteristics were calculated based on the observed prevalence of panic disorder in the medical and psychosomatic subsample, respectively. RESULTS: Panic disorder was diagnosed in 4.3% of the medical outpatients and in 19.2% of the psychosomatic outpatients. The HADS, PHQ, and screening question achieved good operating characteristics. In contrast, physicians detected only 15% of cases with panic disorder. Modified evaluation algorithms of the questionnaires lead to an improvement of test characteristics. Of all measures, the PHQ had the best operating characteristics. The use of screening questionnaires was accepted by 96% of the patients and 97% of the physicians. CONCLUSIONS: The questionnaires as well as the screening question performed well in detecting panic disorder. Thus, the integration of these highly accepted measures into clinical evaluation is suggested. Recommendations for the selection of specific evaluation algorithms are given.

Efficacy and safety of acupuncture for chronic pain caused by gonarthrosis: a study protocol of an ongoing multi-centre randomised controlled clinical trial [ISRCTN27450856].

BACKGROUND: Controlled clinical trials produced contradictory results with respect to a specific analgesic effect of acupuncture. There is a lack of large multi-centre acupuncture trials. The German Acupuncture Trial represents the largest multi-centre study of acupuncture in the treatment of chronic pain caused by gonarthrosis up to now. METHODS: 900 patients will be randomised to three treatment arms. One group receives verum acupuncture, the second sham acupuncture, and the third conservative standard therapy. The trial protocol is described with eligibility criteria, detailed information on the treatment definition, blinding, endpoints, safety evaluation, statistical methods, sample size determination, monitoring, legal aspects, and the current status of the trial. DISCUSSION: A critical discussion is given regarding the considerations about standardisation of the acupuncture treatment, the choice of the control group, and the blinding of patients and observers.

Can noncontact mapping distinguish between endo- and epicardial foci?

OBJECTIVES: Noncontact mapping has been demonstrated to facilitate RF ablation of ventricular arrhythmias, but the reproducibility in the localization of endocardial exit sites during focal ventricular tachycardia ("VT") originating from defined myocardial layers has not been systematically studied. Furthermore, it remains unclear whether noncontact mapping can distinguish between endo- and epicardial foci. METHODS: In six dogs, constant pacing was applied through octopolar needle electrodes in the left ventricle to mimic VT of subendocardial, midmyocardial (mid1; mid2) or subepicardial origin. Using noncontact mapping, the site of origin was determined for each of 50 consecutive beats of all "VTs" and the variation between respective exit sites was measured. Exit sites were reconstructed for 50 consecutive beats of each "VT" and the time span between site of origin and exit site was measured as a parameter of intramural conduction. RESULTS: While subendocardial and midmyocardial (mid1, mid2) foci were pinpointed with a variation of